TETRACYCLIC COMPOUND

Abstract

A compound represented by the general Formula (I) below, or a salt or solvate thereof, which is useful as an ALK inhibitor, and is useful for prophylaxis or treatment of a disease accompanied by abnormality in ALK, for example, cancer, cancer metastasis, depression or cognitive function disorder:

##STR00001## (meanings of the symbols that are included in the formula are as given in the specification).

Claims

1. A compound or salt or solvate thereof represented by Formula (I): ##STR01234## wherein, A.sup.1, A.sup.2, A.sup.3, A.sup.4, A.sup.7, A.sup.8, A.sup.9 and A.sup.10 all represent C, or any one of A.sup.2, A.sup.3, A.sup.4, A.sup.7, A.sup.8 and A.sup.9 represents N (with the proviso that, when it represents N, no substituent group exists therefor) and the remainings represent C; A.sup.5 is selected from NR.sup.5, O and S; R.sup.1 and R.sup.10 each independently represent [1] a hydrogen atom, [2] a cyano group, [3] a halogen atom or [4] a 4- to 10-membered heterocycloalkyl group which may be substituted by 4- to 10-membered heterocycloalkyl group(s); R.sup.2 is selected from the group consisting of: (1) a hydrogen atom, (2) a C.sub.1-8 alkyl group, (3) a C.sub.2-8 alkenyl group, (4) a C.sub.2-8 alkynyl group, (5) a cyano group, (6) a halogen atom, (7) a (C.sub.1-8 alkyl).sub.m2-amino group which may be substituted by C.sub.1-8 alkylsulfonyl group(s), m2: 02, and (8) a nitro group; R.sup.3 is selected from the group consisting of: (1) a hydrogen atom, (2) a C.sub.1-8 alkyl group which may be substituted by [1] halogen atom(s), [2]hydroxy group(s) or [3] C.sub.1-8 alkoxy group(s), (3) a C.sub.6-10 aryl group, (4) a cyano group, (5) a C.sub.1-8 alkanoyl group which may be substituted by C.sub.6-10 aryl group(s), (6) a (C.sub.1-8 alkyl).sub.m3a-aminocarbonyl group which may be substituted by one or more R.sup.3A, R.sup.3A: [1] a C.sub.6-10 aryl group, [2] a C.sub.1-8 alkoxy group, [3] a 5- to 14-membered heteroaryl group, or [4] a C.sub.6-10 arylsulfonyl group, m3a: 02, (7) a hydroxycarbonyl group, (8) a C.sub.1-8 alkoxycarbonyl group which may be substituted by [1] hydroxy group(s) or [2] C.sub.1-8 alkoxy group(s), (9) a halogen atom, (10) a (C.sub.1-8 alkyl).sub.m3b-amino group which may be substituted by C.sub.6-10 aryl group(s), m3b: 02, (11) a C.sub.1-8 alkylcarbonyl (C.sub.0-8 alkyl) amino group which may be substituted by [1]C.sub.6-10 aryl group(s) or [2] C.sub.6-10 aryloxy group(s), (12) a C.sub.6-10 arylcarbonyl (C.sub.0-8 alkyl) amino group which may be substituted by C.sub.1-8 alkyl group(s) which may be substituted by halogen atom(s), (13) a (C.sub.1-8 alkyl).sub.m3c-aminocarbonyl (C.sub.0-8 alkyl) amino group which may be substituted by C.sub.6-10 aryl group(s), m3c: 02, (14) a nitro group, (15) a hydroxy group, (16) a C.sub.1-8 alkoxy group which may be substituted by one or more R.sup.3B, R.sup.3B: [1] a hydroxy group, [2] a C.sub.1-8 alkoxy group, [3] a C.sub.6-10 aryl (C.sub.0-8 alkyl) aminocarbonyl group, [4] a (C.sub.1-8 alkyl).sub.m3d-amino group, or [5] a halogen atom, m3d: 02, (17) a 4- to 10-membered heterocycloalkyloxy group, (18) a 5- to 14-membered heteroaryloxy group, (19) a (C.sub.1-8 alkyl).sub.m3e-aminocarbonyloxy group which may be substituted by C.sub.6-10 aryl group(s) m3e: 02, (20) a 4- to 10-membered nitrogen-containing heterocycloalkylcarbonyl group, (21) a C.sub.1-8 alkylsulfonyloxy group which may be substituted by halogen atom(s), (22) a C.sub.1-8 alkylthio group, (23) a C.sub.1-8 alkylsulfonyl group which may be substituted by C.sub.6-10 aryl group(s), (24) a 5- to 14-membered heteroaryl group which may be substituted by C.sub.1-8 alkyl group(s) which may be substituted by C.sub.1-8 alkoxy group(s), (25) a C.sub.1-8 alkoxycarbonyl (C.sub.0-8 alkyl) amino group which may be substituted by C.sub.1-8 alkoxy group(s), (26) a C.sub.6-10 aryloxycarbonyl (C.sub.0-8 alkyl) amino group which may be substituted by C.sub.1-8 alkyl group(s) which may be substituted by halogen atom(s), (27) a C.sub.6-10 aryl (C.sub.0-8 alkyl) aminocarbonyl (C.sub.0-8 alkyl) amino group which may be substituted by one or more R.sup.3C, R.sup.3C: [1] a C.sub.1-8 alkyl group which may be substituted by halogen atom(s), or [2] a C.sub.1-8 alkoxy group, (28) a C.sub.3-8 cycloalkyl (C.sub.0-8 alkyl) aminocarbonyloxy group, and (29) a C.sub.6-10 aryl (C.sub.0-8 alkyl) aminocarbonyloxy group which may be substituted by substituent(s) selected from the group consisting of [1] a C.sub.1-8 alkyl group and [2] a C.sub.1-8 alkoxy group; R.sup.4 is selected from the group consisting of: (1) a hydrogen atom, (2) a C.sub.1-8 alkyl group which may be substituted by halogen atom(s), (3) a C.sub.2-8 alkenyl group, (4) a C.sub.2-8 alkynyl group, (5) a C.sub.3-8 cycloalkyl group, (6) a cyano group, (7) an aminocarbonyl group, (8) a (C.sub.1-8 alkyl).sub.m4a-aminocarbonyl group, m4a: 12, (9) a hydroxycarbonyl group, (10) a C.sub.1-8 alkoxycarbonyl group, (11) a halogen atom, (12) a (C.sub.1-8 alkyl).sub.m4b-amino group, m4b: 02, (13) a hydroxy group, and (14) a C.sub.1-8 alkoxy group which may be substituted by hydroxy group(s); R.sup.5 is selected from the group consisting of: (1) a hydrogen atom, (2) a C.sub.1-8 alkyl group which may be substituted by one or more R.sup.5A, R.sup.5A: [1] a hydroxycarbonyl group, [2] a C.sub.1-8 alkoxycarbonyl group, [3] a hydroxy group, [4] a C.sub.1-8 alkoxy group, [5] a (C.sub.1-8 alkyl).sub.m5-amino group, [6] a C.sub.6-10 aryl group, or [7] a C.sub.1-8 alkylthio group, m5: 02, (3) a C.sub.2-8 alkenyl group, (4) a C.sub.2-8 alkynyl group, (5) a C.sub.3-8 cycloalkyl group, and (6) a C.sub.1-8 alkylsulfonyl group; R.sup.6 and R.sup.6 are each independently selected from the group consisting of: (1) a C.sub.1-8 alkyl group which may be substituted by halogen atom(s), (2) a C.sub.2-8 alkenyl group, and (3) a C.sub.2-8 alkynyl group; or R.sup.6 and R.sup.6 are taken together with the carbon atoms to which they are bound to form: (4) a C.sub.3-8 cycloalkyl group, or (5) a 4- to 10-membered heterocycloalkyl group which may be substituted by C.sub.1-8 alkyl C.sub.6-10 aryl sulfonyl group(s) which may be substituted by C.sub.1-8 alkyl group(s); R.sup.7 is selected from the group consisting of: (1) a hydrogen atom, (2) a halogen atom, (3) a C.sub.1-8 alkoxy group which may be substituted by one or more R.sup.7A, R.sup.7A: [1] a (C.sub.1-8 alkyl).sub.m7a-amino group, [2] a hydroxy, [3] a 4- to 10-membered heterocycloalkyl group which may be substituted by C.sub.1-8 alkyl group(s), m7a: 02, (4) a C.sub.1-8 alkylsulfonyl group, (5) a nitro group, and (6) a hydroxyl group; R.sup.8 is selected from the group consisting of: (1) a hydrogen atom, (2) a C.sub.1-8 alkyl group which may be substituted by one or more R.sup.8A, R.sup.8A: [1] a 4- to 10-membered heterocycloalkyl group which may be substituted by one or more R.sup.8A, [2] a (C.sub.1-8 alkyl).sub.m8a-amino group which may be substituted by a halogen atom, or [3] a hydroxy group, m8a: 02, R.sup.8A: [1] a C.sub.1-8 alkyl group, [2] a C.sub.1-8 alkylsulfonyl group, [3] a (C.sub.1-8 alkyl).sub.m8b-aminosulfonyl group, [4] an oxo group, [5] a C.sub.1-8 alkoxycarbonyl, or [6] a C.sub.1-8 alkoxycarbonyl (C.sub.0-8 alkyl) aminosulfonyl, m8b: 02, (3) a C.sub.2-8 alkenyl group, (4) a 4- to 10-membered heterocycloalkyl group which may be substituted by one or more R.sup.8B, R.sup.8B: <1> a C.sub.1-8 alkyl group which may be substituted by one or more R.sup.8B1, <2> a C.sub.2-8 alkeynyl group, <3> a C.sub.2-8 alkynyl group, <4> a C.sub.3-8 cycloalkyl group which may be substituted by [1] cyano group(s) or [2] C.sub.1-8 alkyl group(s), <5> a 4- to 10-membered heterocycloalkyl group which may be substituted by one or more R.sup.8B2, <6> a C.sub.1-8 alkoxy group which may be substituted by substituent(s) selected from the group consisting of [1] a C.sub.1-8 alkoxy group and [2] a C.sub.3-8 cycloalkyl group, <7> a C.sub.1-8 alkoxycarbonyl group, <8> a C.sub.1-8 alkylsulfonyl group, <9> a 5- to 14-membered heteroarylsulfonyl group, <10> an oxo group, <11> a cyano group, <12> a C.sub.1-8 alkanoyl group which may be substituted by one or more R.sup.8B3, <13> a C.sub.3-8 cycloalkylcarbonyl group, <14> a (C.sub.1-8 alkyl).sub.m8c-aminosulfonyl group, <15> a C.sub.1-8 alkylsulfonyl (C.sub.0-8 alkyl) amino group, <16> a (C.sub.1-8 alkyl).sub.m8d-amino group which may be substituted by one or more R.sup.8B4, <17> a hydroxy group, <18> a (C.sub.1-8 alkyl).sub.m8e-aminocarbonyl group, or <19> a C.sub.1-8 alkoxycarbonyl (C.sub.0-8 alkyl) amino group m8c: 02 m8d: 02 m8e: 02 R.sup.8B1: [1] a C.sub.3-8 cycloalkyl group, [2] a hydroxy group, or [3] a C.sub.1-8 alkoxy group(s), R.sup.8B2: [1] a halogen atom, [2] a C.sub.1-8 alkyl group, [3] an oxo group, [4] a hydroxy group, or [5] a deuterium atom, R.sup.8B3: a (C.sub.1-8 alkyl).sub.m8f-amino group, m8f: 02, R.sup.8B4: [1] a C.sub.3-8 cycloalkyl group, or [2] a hydroxy group, (5) a 5- to 14-membered heteroaryl group which may be substituted by a C.sub.1-8 alkyl group, (6) a (C.sub.1-8 alkyl).sub.m8g-aminocarbonyl group which may be substituted by one or more R.sup.8C, m8g: 02, R.sup.8C: [1] a hydroxy group, [2] a (C.sub.1-8 alkyl).sub.m8h-amino group which may be substituted by substituent(s) selected from the group consisting of <1> a (C.sub.1-8 alkyl).sub.m8i-aminosulfonyl group, <2> a C.sub.1-8 alkylsulfonyl group, <3> a C.sub.1-8 alkoxycarbonyl group and <4> a C.sub.1-8 alkoxycarbonyl(C.sub.0-8 alkyl) aminosulfonyl group, [3] a C.sub.1-8 alkylsulfonyl group, or [4] a C.sub.1-8 alkoxy group which may be substituted by a hydroxy group, m8h: 02, m8i: 02, (7) a 4- to 10-membered heterocycloalkyl (C.sub.0-8 alkyl) aminocarbonyl group which may be substituted by oxo group(s), (8) a 4- to 10-membered nitrogen-containing heterocycloalkylcarbonyl group which may be substituted by one or more R.sup.8D, R.sup.8D: [1] a C.sub.1-8 alkyl group which may be substituted by one or more R.sup.8D1, [2] a hydroxy group, [3] a C.sub.1-8 alkylsulfonyl group, or [4] a C.sub.1-8 alkoxycarbonyl group, R.sup.8D1: [1] a hydroxy group, or [2] a C.sub.1-8 alkoxy group, (9) a hydroxycarbonyl group, (10) a C.sub.0-8 alkoxy (C.sub.0-8 alkyl) aminocarbonyl group which may be substituted by hydroxy group(s), (11) a halogen atom, (12) a (C.sub.1-8 alkyl).sub.m8j-amino group which may be substituted by one or more R.sup.8H, m8j: 02, R.sup.8H: [1] a hydroxy group, or [2] a 4- to 10-membered heterocycloalkyl group, (13) a hydroxyl group, (14) a C.sub.1-8 alkoxy group which may be substituted by one or more R.sup.8E, R.sup.8E: <1> a hydroxy group, <2> halogen atom, <3> a hydroxycarbonyl group, <4> a C.sub.1-8 alkoxycarbonyl group, <5> a 4- to 10-membered nitrogen-containing heterocycloalkylcarbonyl group which may be substituted by one or more R.sup.8E1, <6> a (C.sub.1-8 alkyl).sub.m8k1-amino group which may be substituted by one or more R.sup.8E2, m8k1: 02, <7> a 4- to 10-membered heterocycloalkyl group which may be substituted by one or more R.sup.8E3, <8> a 5- to 14-membered heteroaryl group, <9> a (C.sub.1-8 alkyl).sub.m8k2-aminocarbonyl group which may be substituted by one or more R.sup.8E6, m8k2: 02, <10> a C.sub.1-8 alkoxy group which may be substituted by one or more R.sup.8E7, <11> a C.sub.1-8 alkylthio group, <12> a C.sub.1-8 alkylsulfinyl group, <13> a C.sub.1-8 alkylsulfonyl group, R.sup.8E1: <1> a C.sub.1-8 alkoxycarbonyl group, <2> a C.sub.1-8 alkanoyl group, <3> a C.sub.1-8 alkylsulfonyl group, <4> a (C.sub.1-8 alkyl).sub.m8k3-aminosulfonyl group, m8k3: 02, or <5> a 4- to 10-membered heterocycloalkyl group, R.sup.8E2: <1> a hydroxy group, <2> a C.sub.1-8 alkoxycarbonyl group which may be substituted by halogen atom(s), <3> a C.sub.3-8 cycloalkyl group which may be substituted by C.sub.1-8 alkyl group(s) which may be substituted by hydroxy group(s), <4> a C.sub.1-8 alkanoyl group which may be substituted by substituent(s) selected from the group consisting of [1] a (C.sub.1-8 alkyl).sub.m8k4-amino group and [2] a halogen atom(s), m8k4: 02, <5> a (C.sub.1-8 alkyl).sub.m8k5-aminocarbonyl group, m8k5: 02, <6> a C.sub.1-8 alkylsulfonyl group, <7> a 4- to 10-membered nitrogen-containing heterocycloalkylsulfonyl group which may be substituted by C.sub.1-8 alkyl group(s), <8> a (C.sub.1-8 alkyl).sub.m8k6-aminosulfonyl group which may be substituted by C.sub.1-8 alkoxycarbonyl group(s), m8k6: 02, or R.sup.8E3: <1> a C.sub.1-8 alkyl group which may be substituted by substituent(s) selected from the group consisting of [1] a hydroxy group and [2] a C.sub.1-8 alkylcarbonyloxy group, <2> a C.sub.1-8 alkylcarbonyloxy group, <3> a hydroxy group, <4> a C.sub.3-8 cycloalkyl group, <5> a C.sub.1-8 alkoxy group, <6> a C.sub.1-8 alkoxycarbonyl group, <7> a C.sub.1-8 alkylsulfonyl group, <8> a (C.sub.1-8 alkyl).sub.m8k8-aminocarbonyl group m8k8: 02, <9> a C.sub.1-8 alkanoyl group which may be substituted by hydroxy group(s), <10> an oxo group, or <11> a 4- to 10-membered heterocycloalkyl group which may be substituted by substituent(s) selected from the group consisting of [1] a C.sub.1-8 alkanoyl group, [2] a C.sub.1-8 alkoxycarbonyl group and [3] a C.sub.1-8 alkylsulfonyl group, R.sup.8E6: <1> a C.sub.2-8 alkenylcarbonyloxy group, <2> a hydroxy group, <3> a cyano group, <4> a (C.sub.1-8 alkyl).sub.m8k9-amino group which may be substituted by hydroxy group(s) m8k9: 02, <5> a C.sub.1-8 alkoxy group which may be substituted by hydroxy group(s), <6> a C.sub.1-8 alkylcarbonyloxy group, <7> a 4- to 10-membered heterocycloalkyl group which may be substituted by C.sub.1-8 alkyl group(s), or <8> a 5- to 14-membered heteroaryl group, R.sup.8E7: <1> a hydroxy group, or <2> a C.sub.1-8 alkoxy group which may be substituted by hydroxy group(s), (15) a 4- to 10-membered heterocycloalkyloxy group which may be substituted by one or more R.sup.8F, R.sup.8F: <1> a C.sub.1-8 alkyl group which may be substituted by one or more R.sup.8F1, <2> a C.sub.3-8 cycloalkyl group, <3> a C.sub.1-8 alkanoyl group which may be substituted by halogen atom(s), <4> a C.sub.1-8 alkylcarbonyloxy group, <5> a C.sub.1-8 alkoxycarbonyl group, <6> a 4- to 10-membered heterocycloalkyl group which may be substituted by one or more R.sup.8F2, <7> a C.sub.1-8 alkyl sulfonyl group, <8> a hydroxy group, or [9] a C.sub.6-10 aryl group, R.sup.8F1: [1] a hydroxy group, [2] a C.sub.1-8 alkoxy group, or [3] a halogen atom, R.sup.8F2: [1] a 4- to 10-membered heterocycloalkyl group, [2] a C.sub.1-8 alkoxycarbonyl group, or [3] a C.sub.1-8 alkylsulfonyl group, (16) a 5- to 14-membered heteroaryloxy group, (17) a 4- to 10-membered heterocycloalkylcarbonyloxy group, (18) a (C.sub.1-8 alkyl).sub.m8l1-aminosulfonyloxy group, m8l1: 02, (19) a C.sub.1-8 alkyl thio group which may be substituted by [1] (C.sub.1-8 alkyl).sub.m8l2-amino group(s), [2] hydroxy group(s) or [3] hydroxycarbonyl group(s), m8l2: 02, (20) a C.sub.1-8 alkylsulfonyl group which may be substituted by one or more R.sup.8G, R.sup.8G: [1] a hydroxycarbonyl group, [2] a hydroxy group, or [3] a (C.sub.1-8 alkyl).sub.m8l3-amino group, m8l3: 02, (21) a 4- to 10-membered nitrogen-containing heterocycloalkylsulfonyloxy group which may be substituted by C.sub.1-8 alkyl group(s), (22) a C.sub.2-8 alkenyloxy group, and (23) a C.sub.1-8 alkylsulfonyloxy group which may be substituted by halogen atom(s); R.sup.9 is selected from the group consisting of: (1) a hydrogen atom, (2) a C.sub.1-8 alkyl group which may be substituted by one or more R.sup.9A, R.sup.9A: [1] a C.sub.3-8 cycloalkyl group, [2] a 4- to 10-membered heterocycloalkyl group which may be substituted by one or more R.sup.9A1, [3] a hydroxy group, [4] a C.sub.1-8 alkoxy group, or [5] a hydroxycarbonyl group, R.sup.9A1: [1] a C.sub.1-8 alkyl group, [2] a C.sub.3-8 cycloalkyl group, or [3] a 4- to 10-membered heterocycloalkyl group, (3) a C.sub.2-8 alkenyl group which may be substituted by one or more R.sup.9B, R.sup.9B: [1] a (C.sub.1-8 alkyl).sub.m9a-amino group, [2] a 4- to 10-membered heterocycloalkyl group which may be substituted by one or more group R.sup.9B1, R.sup.9B1: [1] a C.sub.3-8 cycloalkyl group, or [2] a 4- to 10-membered heterocycloalkyl group, m9a: 02, (4) a C.sub.2-8 alkynyl group which may be substituted by one or more R.sup.9C, R.sup.9C: [1] a C.sub.1-8 alkoxy group, [2] a (C.sub.1-8 alkyl).sub.m9b-amino group which may be substituted by C.sub.6-10 aryl group(s), [3] a 4- to 10-membered heterocycloalkyl group which may be substituted by one or more R.sup.9C1, [4] a C.sub.3-8 cycloalkyl group, [5] a hydroxy group, [6] a hydroxycarbonyl group, or [7] a C.sub.1-8 alkyloxycarbonyl group, m9b: 02, R.sup.9C1: [1] a C.sub.3-8 cycloalkyl group, [2] a 4- to 10-membered heterocycloalkyl group, or [3] an oxo group, (5) a C.sub.3-8 cycloalkyl group, (6) a 4- to 10-membered heterocycloalkyl group which may be substituted by one or more R.sup.9D, R.sup.9D: [1] a C.sub.1-8 alkyl group which may be substituted by 4- to 10-membered heterocycloalkyl group(s), [2] a C.sub.3-8 cycloalkyl group, [3] a 4- to 10-membered heterocycloalkyl group, or [4] a C.sub.1-6 alkylsulfonyl group, or [5] a C.sub.1-8 alkoxycarbonyl group, (7) a C.sub.6-10 aryl group which may be substituted by one or more R.sup.9E, R.sup.9E: [1] a halogen atom, [2] a hydroxy group, [3] a hydroxycarbonyl group, or [4] a C.sub.1-8 alkyl group which may be substituted by hydroxy group(s), or [5] a C.sub.1-8 alkoxy group, (8) a 5- to 14-membered heteroaryl group which may be substituted by C.sub.1-8 alkyl group(s), (9) a cyano group, (10) a C.sub.1-8 alkanoyl group, (11) a 4- to 10-membered nitrogen-containing heterocycloalkylcarbonyl group which may be substituted by C.sub.1-8 alkyl group(s), (12) a halogen atom, (13) a (C.sub.1-8 alkyl).sub.m9c-amino group which may be substituted by one or more R.sup.9F, m9c: 02, (14) a C.sub.1-8 alkylcarbonyl(C.sub.0-8 alkyl)amino group which may be substituted by (C.sub.1-8 alkyl).sub.m9d-amino group(s), m9d: 02, (15) a C.sub.1-8 alkylsulfonyl(C.sub.0-8 alkyl)amino group, (16) a (C.sub.1-8 alkyl).sub.m9e-aminosulfonyl(C.sub.0-8 alkyl)amino group, m9e: 02, (17) a nitro group, (18) a hydroxy group, (19) a C.sub.1-8 alkoxy group which may be substituted by one or more R.sup.9G, R.sup.9G: [1] a hydroxy group, [2] a hydroxycarbonyl group, [3] a C.sub.6-10 aryl group which may be substituted by C.sub.1-8 alkoxy group(s), [4] a (C.sub.1-8 alkyl).sub.m9g1-amino group, [5] a C.sub.1-8 alkoxy group which may be substituted by one or more R.sup.9G1, [6] a 5- to 14-membered heteroaryl group, or [7] a 4- to 10-membered heterocycloalkyloxy group which may be substituted by C.sub.1-8 alkyl group(s), m9g1: 02, R.sup.9G1: [1] a C.sub.1-8 alkoxy group, or [2] a hydroxycarbonyl group, (20) a 4- to 10-membered heterocycloalkyloxy group which may be substituted by [1] 4- to 10-membered heterocycloalkyl group(s), or [2] C.sub.1-8 alkoxycarbonyl group(s), (21) a C.sub.1-8 alkylsulfonyloxy group which may be substituted by halogen atom(s), (22) a C.sub.1-8 alkylthio group which may be substituted by (C.sub.1-8 alkyl).sub.m9f-amino group(s), m9f: 02, (23) a C.sub.1-8 alkylsulfonyl group which may be substituted by (C.sub.1-8 alkyl).sub.m9g-amino group(s), m9g: 02, (24) a (C.sub.1-8 alkyl).sub.m9h-aminosulfonyl group, m9h: 02, (25) a 4- to 10-membered nitrogen-containing heterocycloalkylsulfonyl group which may be substituted by C.sub.1-8 alkyl group(s), and (26) a hydroxycarbonyl group.

2. The compound according to claim 1, or a salt or solvate thereof, wherein R.sup.3 is a cyano group or a halogen atom.

3. The compound according to claim 1, or a salt or solvate thereof, wherein A.sup.5 is NR.sup.5 and R.sup.5 is a hydrogen atom.

4. The compound according to claim 1, or a salt or solvate thereof, wherein all of the A.sup.1, A.sup.2, A.sup.3, A.sup.4, A.sup.7, A.sup.8, A.sup.9 and A.sup.10 are a carbon atom.

5. The compound according to claim 1, or a salt or solvate thereof, wherein: A.sup.1, A.sup.2, A.sup.3, A.sup.4, A.sup.7, A.sup.8, A.sup.9 and A.sup.10 all represent C, or any one of A.sup.2, A.sup.3, A.sup.4, A.sup.7, A.sup.8 and A.sup.9 represents N (with the proviso that, when it represents N, no substituent group exists therefor) and the remainings represent C; A.sup.5 is selected from NR.sup.5, O and S; R.sup.1 represents [1] a hydrogen atom, [2] a cyano group, or [3] a halogen atom; R.sup.2 is selected from the group consisting of: (1) a hydrogen atom, (2) a C.sub.1-8 alkyl group, (3) a cyano group, (4) a halogen atom, and (5) a (C.sub.1-8 alkyl).sub.m2-amino group which may be substituted by C.sub.1-8 alkylsulfonyl group(s), m2: 02; R.sup.3 is selected from the group consisting of: (1) a hydrogen atom, (2) a C.sub.1-8 alkyl group which may be substituted by halogen atom(s), (3) a cyano group, (4) a (C.sub.1-8 alkyl).sub.m3a-aminocarbonyl group which may be substituted by one or more R.sup.3A, R.sup.3A: [1] a C.sub.6-10 aryl group, [2] a C.sub.1-8 alkoxy group, [3] a 5- to 14-membered heteroaryl group, or [4] a C.sub.6-10 aryl sulfonyl group, m3a: 02, (5) a hydroxycarbonyl group, (6) a C.sub.1-8 alkoxycarbonyl group which may be substituted by hydroxy group(s), (7) a halogen atom, (8) a (C.sub.1-8 alkyl).sub.m3b-amino group which may be substituted by C.sub.6-10 aryl group(s), m3b: 02, (9) a C.sub.1-8 alkylcarbonyl (C.sub.0-8 alkyl) amino group which may be substituted by [1]C.sub.6-10 aryl group(s) or [2] C.sub.6-10 aryloxy group(s), (10) a C.sub.6-10 arylcarbonyl (C.sub.0-8 alkyl) amino group which may be substituted by C.sub.1-8 alkyl group(s) which may be substituted by halogen atom(s), (11) a nitro group, (12) a hydroxy group, (13) a C.sub.1-8 alkoxy group which may be substituted by one or more R.sup.3B, R.sup.3B: [1] a hydroxy group, [2] a C.sub.1-8 alkoxy group, [3] a C.sub.6-10 aryl (C.sub.0-8 alkyl) aminocarbonyl group, [4] a (C.sub.1-8 alkyl).sub.m3d-amino group, or [5] a halogen atom, m3d: 02, (14) a 4- to 10-membered heterocycloalkyloxy group, (15) a 5- to 14-membered heteroaryloxy group, (16) a (C.sub.1-8 alkyl).sub.m3e-aminocarbonyloxy group which may be substituted by C.sub.6-10 aryl group(s), m3e: 02, (17) a 4- to 10-membered nitrogen-containing heterocycloalkylcarbonyl group, (18) a C.sub.1-8 alkylthio group, (19) a 5- to 14-membered heteroaryl group which may be substituted by C.sub.1-8 alkyl group(s) which may be substituted by C.sub.1-8 alkoxy group(s), (20) a C.sub.1-8 alkoxycarbonyl (C.sub.0-8 alkyl) amino group which may be substituted by C.sub.1-8 alkoxy group(s), (21) a C.sub.6-10 aryloxycarbonyl (C.sub.0-8 alkyl) amino group which may be substituted by C.sub.1-8 alkyl group(s) which may be substituted by halogen atom(s), (22) a C.sub.6-10 aryl (C.sub.0-8 alkyl) aminocarbonyl (C.sub.0-8 alkyl) amino group which may be substituted by C.sub.1-8 alkoxy group(s), (23) a C.sub.3-8 cycloalkyl (C.sub.0-8 alkyl) aminocarbonyloxy group, and (24) a C.sub.6-10 aryl (C.sub.0-8 alkyl) aminocarbonyloxy group which may be substituted by substituent(s) selected from the group consisting of [1] a C.sub.1-8 alkyl group and [2] a C.sub.1-8 alkoxy group; R.sup.4 is selected from the group consisting of: (1) a hydrogen atom, (2) a C.sub.1-8 alkyl group which may be substituted by halogen atom(s), (3) a C.sub.3-8 cycloalkyl group, (4) a cyano group, (5) an aminocarbonyl group, (6) a hydroxycarbonyl group, (7) a halogen atom, (8) a (C.sub.1-8 alkyl).sub.m4b-amino group, m4b: 02, (9) a hydroxy group, and (10) a C.sub.1-8 alkoxy group which may be substituted by hydroxy group(s); R.sup.5 is selected from the group consisting of: (1) a hydrogen atom, (2) a C.sub.1-8 alkyl group which may be substituted by one or more R.sup.5A, R.sup.5A: [1] a hydroxycarbonyl group, [2] a C.sub.1-8 alkoxycarbonyl group, [3] a hydroxy group, [4] a C.sub.1-8 alkoxy group, [5] a (C.sub.1-8 alkyl).sub.m5-amino group, or [6] a C.sub.1-8 alkylthio group, m5: 02, and (3) a C.sub.1-8 alkylsulfonyl group; R.sup.6 and R.sup.6 are each independently: (1) a C.sub.1-8 alkyl group, or R.sup.6 and R.sup.6 are taken together with the carbon atoms to which they are bound to form, (2) a C.sub.3-8 cycloalkyl group, or (3) a 4- to 10-membered heterocycloalkyl group; R.sup.7 is selected from the group consisting of: (1) a hydrogen atom, (2) a halogen atom, and (3) a C.sub.1-8 alkoxy group which may be substituted by one or more R.sup.7A, R.sup.7A: [1] a (C.sub.1-8 alkyl).sub.m7a-amino group, or [2] a hydroxy group, m7a: 0-2; R.sup.8 is selected from the group consisting of: (1) a hydrogen atom, (2) a C.sub.1-8 alkyl group which may be substituted by one or more R.sup.8A, R.sup.8A: [1] a 4- to 10-membered heterocycloalkyl group which may be substituted by one or more R.sup.8A1, [2] a (C.sub.1-8 alkyl).sub.m8a-amino group which may be substituted by a halogen atom, or [3] a hydroxy group, m8a: 0-2, R.sup.8A1: [1] a C.sub.1-8 alkyl group, [2] a C.sub.1-8 alkylsulfonyl group, [3] a (C.sub.1-8 alkyl).sub.m8b- aminosulfonyl group, or [4] an oxo group, m8b: 02, (3) a C.sub.2-8 alkenyl group, (4) a 4- to 10-membered heterocycloalkyl group which may be substituted by one or more R.sup.8B, R.sup.8B: <1> a C.sub.1-8 alkyl group which may be substituted by one or more R.sup.8B1, <2> a C.sub.2-8 alkynyl group, <3> a C.sub.3-8 cycloalkyl group which may be substituted by [1] cyano group(s) or [2] C.sub.1-8 alkyl group(s), <4> a 4- to 10-membered heterocycloalkyl group which may be substituted by one or more R.sup.8B2, <5> a C.sub.1-8 alkoxy group which may be substituted by substituent(s) selected from the group consisting of [1] a C.sub.1-8 alkoxy group and [2] a C.sub.3-8 cycloalkyl group, <6> a C.sub.1-8 alkylsulfonyl group, <7> an oxo group, <8> a cyano group, <9> a C.sub.1-8 alkanoyl group which may be substituted by one or more R.sup.8B3, <10> a C.sub.3-8 cycloalkylcarbonyl group, <11> a (C.sub.1-8 alkyl).sub.m8c-aminosulfonyl group, <12> a C.sub.1-8 alkylsulfonyl (C.sub.0-8 alkyl) amino group, <13> a (C.sub.1-8 alkyl).sub.m8d-amino group which may be substituted by one or more R.sup.8B4, <14> a hydroxy group, or <15> a (C.sub.1-8 alkyl).sub.m8e-aminocarbonyl group, m8c: 02, m8d: 02, m8e: 02, R.sup.8B1: [1] a C.sub.3-8 cycloalkyl group, [2] a hydroxy group, or [3] C.sub.1-8 alkoxy group which may be substituted by C.sub.1-8 alkoxy group(s), R.sup.8B2: [1] a halogen atom, [2] a C.sub.1-8 alkyl group, [3] an oxo group, or [4] a hydroxy group, R.sup.8B3: a (C.sub.1-8 alkyl).sub.m8f-amino group, m8f: 02, R.sup.8B4: [1] a C.sub.3-8 cycloalkyl group, or [2] a hydroxy group, (5) a 5- to 14-membered heteroaryl group which may be substituted by a C.sub.1-8 alkyl group, (6) a (C.sub.1-8 alkyl).sub.m8g-aminocarbonyl group which may be substituted by one or more R.sup.8C, m8g: 02, R.sup.8C: [1] a hydroxy group, [2] a (C.sub.1-8 alkyl).sub.m8h-amino group which may be substituted by substituent(s) selected from the group consisting of <1> a (C.sub.1-8 alkyl).sub.m8i-aminosulfonyl group and <2> a C.sub.1-8 alkylsulfonyl group, or [3] a C.sub.1-8 alkylsulfonyl group, m8h: 02, m8i: 02, (7) a 4- to 10-membered heterocycloalkyl (C.sub.0-8 alkyl) aminocarbonyl group which may be substituted by oxo group(s), (8) a 4- to 10-membered nitrogen-containing heterocycloalkylcarbonyl group which may be substituted by one or more R.sup.8D, R.sup.8D: [1] a C.sub.1-8 alkyl group which may be substituted by one or more R.sup.8D1, [2] a hydroxy group, or [3] a C.sub.1-8 alkylsulfonyl group, R.sup.8D1: [1] a hydroxy group, or [2] a C.sub.1-8 alkoxy group, (9) a hydroxycarbonyl group, (10) a C.sub.0-8 alkoxy (C.sub.0-8 alkyl) aminocarbonyl group which may be substituted by hydroxy group(s), (11) a halogen atom, (12) a (C.sub.1-8 alkyl).sub.m8j-amino group which may be substituted by 4- to 10-membered heterocycloalkyl group(s), m8j: 02, (13) a hydroxyl group, (14) a C.sub.1-8 alkoxy group which may be substituted by one or more R.sup.E, R.sup.8E: <1> a hydroxy group, <2> a C.sub.1-8 alkoxycarbonyl group, <3> a 4- to 10-membered nitrogen-containing heterocycloalkylcarbonyl group which may be substituted by one or more R.sup.8E1, <4> a (C.sub.1-8 alkyl).sub.m8k1-amino group which may be substituted by one or more R.sup.8E2, m8k1: 02, <5> a 4- to 10-membered heterocycloalkyl group which may be substituted by one or more R.sup.8E3, <6> a 5- to 14-membered heteroaryl group, <7> a (C.sub.1-8 alkyl).sub.m8k2-aminocarbonyl group which may be substituted by one or more R.sup.8E6 m8k2: 02, <8> a C.sub.1-8 alkoxy group which may be substituted by one or more R.sup.8E7, <9> a C.sub.1-8 alkylthio group, <10> a C.sub.1-8 alkylsulfinyl group, or <11> a C.sub.1-8 alkylsulfonyl group, R.sup.8E1: <1> a C.sub.1-8 alkoxycarbonyl group, <2> a C.sub.1-8 alkanoyl group, <3> a C.sub.1-8 alkylsulfonyl group, <4> a (C.sub.1-8 alkyl).sub.m8k3-aminosulfonyl group m8k3: 02, or <5> a 4- to 10-membered heterocycloalkyl group, R.sup.8E2: <1> a hydroxy group, <2> a C.sub.1-8 alkoxycarbonyl group, <3> a C.sub.3-8 cycloalkyl group which may be substituted by C.sub.1-8 alkyl group(s) which may be substituted by hydroxy group(s), <4> a C.sub.1-8 alkanoyl group which may be substituted by substituent(s) selected from the group consisting of [1] a (C.sub.1-8 alkyl).sub.m8k4-amino group and [2] a halogen atom, m8k4: 02, <5> a (C.sub.1-8 alkyl).sub.m8k5-aminocarbonyl group, m8k5: 02, <6> a C.sub.1-8 alkylsulfonyl group, <7> a 4- to 10-membered nitrogen-containing heterocycloalkylsulfonyl group which may be substituted by C.sub.1-8 alkyl group(s), <8> a (C.sub.1-8 alkyl).sub.m8k6-aminosulfonyl group, m8k6: 02, or R.sup.8E3: <1> a C.sub.1-8 alkyl group which may be substituted by substituent(s) selected from the group consisting of [1] a hydroxy group and [2] a C.sub.1-8 alkylcarbonyloxy group, <2> a hydroxy group, <3> a C.sub.3-8 cycloalkyl group, <4> a C.sub.1-8 alkylsulfonyl group, <5> a (C.sub.1-8 alkyl).sub.m8k8-aminocarbonyl group, m8k8: 02, <6> a C.sub.1-8 alkanoyl group which may be substituted by hydroxy group(s), <7> an oxo group, or <8> a 4- to 10-membered heterocycloalkyl group which may be substituted by substituent(s) selected from the group consisting of [1] a C.sub.1-8 alkanoyl group, and [2] a C.sub.1-8 alkylsulfonyl group, R.sup.8E6: <1> a C.sub.2-8 alkenylcarbonyloxy group, <2> a hydroxy group, <3> a cyano group, <4> a (C.sub.1-8 alkyl).sub.m8k9-amino group which may be substituted by hydroxy group(s), m8k9: 02, <5> a C.sub.1-8 alkoxy group which may be substituted by hydroxy group(s), <6> a 4- to 10-membered heterocycloalkyl group which may be substituted by C.sub.1-8 alkyl group(s), or <7> a 5- to 14-membered heteroaryl group, R.sup.8E7: <1> a hydroxy group, or <2> a C.sub.1-8 alkoxy group which may be substituted by hydroxy group(s), (15) a 4- to 10-membered heterocycloalkyloxy group which may be substituted by one or more R.sup.8F: R.sup.8F: <1> a C.sub.1-8 alkyl group which may be substituted by one or more R.sup.8F1, <2> a C.sub.3-8 cycloalkyl group, <3> a C.sub.1-8 alkanoyl group which may be substituted by halogen atom(s), <4> a C.sub.1-8 alkoxycarbonyl group, <5> a 4- to 10-membered heterocycloalkyl group which may be substituted by one or more R.sup.8F2, <6> a C.sub.1-8 alkyl sulfonyl group, or <7> a hydroxy group, R.sup.8F1: [1] a hydroxy group, [2] a C.sub.1-8 alkoxy group, or [3] a halogen atom, R.sup.8F2: [1] a 4- to 10-membered heterocycloalkyl group, [2] a C.sub.1-8 alkoxycarbonyl group, or [3] a C.sub.1-8 alkylsulfonyl group, (16) a 5- to 14-membered heteroaryloxy group, (17) a (C.sub.1-8 alkyl).sub.m811-aminosulfonyloxy group, m8l1: 02, (18) a C.sub.1-8 alkylthio group which may be substituted by (C.sub.1-8 alkyl).sub.m8l2-amino group(s), m8l2: 02, (19) a C.sub.1-8 alkylsulfonyl group which may be substituted by one or more R.sup.8G, R.sup.8G: [1] a hydroxycarbonyl group, [2] a hydroxy group, or [3] a (C.sub.1-8 alkyl).sub.m8l3-amino group, m8l3: 02, (20) a C.sub.2-8 alkenyloxy group, and (21) a C.sub.1-8 alkylsulfonyloxy group which may be substituted by halogen atom(s); R.sup.9 is selected from the group consisting of: (1) a hydrogen atom, (2) a C.sub.1-8 alkyl group which may be substituted by one or more R.sup.9A, R.sup.9A: [1] a C.sub.3-8 cycloalkyl group, [2] a 4- to 10-membered heterocycloalkyl group which may be substituted by one or more R.sup.9A1, [3] a hydroxy group, or [4] a C.sub.1-8 alkoxy group, R.sup.9A1: [1] a C.sub.1-8 alkyl group, [2] a C.sub.3-8 cycloalkyl group, or [3] a 4- to 10-membered heterocycloalkyl group, (3) a C.sub.2-8 alkenyl group, (4) a C.sub.2-8 alkynyl group which may be substituted by one or more R.sup.9C, R.sup.9C: [1] a C.sub.1-8 alkoxy group, [2] a (C.sub.1-8 alkyl).sub.m9b-amino group which may be substituted by C.sub.6-10 aryl group(s), [3] a 4- to 10-membered heterocycloalkyl group which may be substituted by one or more R.sup.9C1, [4] a C.sub.3-8 cycloalkyl group, [5] a hydroxy group, or [6] a hydroxycarbonyl group, m9b: 02, R.sup.9C1: [1] a C.sub.3-8 cycloalkyl group, [2] a 4- to 10-membered heterocycloalkyl group, or [3] an oxo group, (5) a C.sub.3-8 cycloalkyl group, (6) a 4- to 10-membered heterocycloalkyl group which may be substituted by one or more R.sup.9D, R.sup.9D: [1] a C.sub.1-8 alkyl group which may be substituted by 4- to 10-membered heterocycloalkyl group(s), [2] a C.sub.3-8 cycloalkyl group, [3] a 4- to 10-membered heterocycloalkyl group, or [4] a C.sub.1-6 alkylsulfonyl group, (7) a C.sub.6-10 aryl group which may be substituted by one or more R.sup.9E, R.sup.9E: [1] a halogen atom, [2] a hydroxy group, [3] a hydroxycarbonyl group, or [4] a C.sub.1-8 alkyl group which may be substituted by hydroxy group(s), (8) a 5- to 14-membered heteroaryl group which may be substituted by C.sub.1-8 alkyl group(s), (9) a cyano group, (10) a C.sub.1-8 alkanoyl group, (11) a 4- to 10-membered nitrogen-containing heterocycloalkylcarbonyl group which may be substituted by C.sub.1-8 alkyl group(s), (12) a halogen atom, (13) a (C.sub.1-8 alkyl).sub.m9c-amino group, m9c: 02, (14) a C.sub.1-8 alkylcarbonyl(C.sub.0-8 alkyl)amino group which may be substituted by (C.sub.1-8 alkyl).sub.m9d-amino group(s), m9d: 02, (15) a C.sub.1-8 alkylsulfonyl(C.sub.0-8 alkyl)amino group, (16) a (C.sub.1-8 alkyl).sub.m9e-aminosulfonyl(C.sub.0-8 alkyl)amino group, m9e: 02, (17) a nitro group, (18) a hydroxy group, (19) a C.sub.1-8 alkoxy group which may be substituted by one or more R.sup.9G, R.sup.9G: [1] a hydroxy group, [2] a hydroxycarbonyl group, [3] a C.sub.6-10 aryl group which may be substituted by C.sub.1-8 alkoxy group(s), [4] a (C.sub.1-8 alkyl).sub.m9g1-amino group, [5] a C.sub.1-8 alkoxy group which may be substituted by one or more R.sup.9G1, or [6] a 5- to 14-membered heteroaryl group, m9g1: 02, R.sup.9G1: [1] a C.sub.1-8 alkoxy group, or [2] a hydroxycarbonyl group, (20) a 4- to 10-membered heterocycloalkyloxy group which may be substituted by 4- to 10-membered heterocycloalkyl group(s), (21) a C.sub.1-8 alkylthio group which may be substituted by (C.sub.1-8 alkyl).sub.m9f-amino group(s), m9f: 02, (22) a C.sub.1-8 alkylsulfonyl group which may be substituted by (C.sub.1-8 alkyl).sub.m9g-amino group(s), m9g: 02, (23) a (C.sub.1-8 alkyl).sub.m9h-aminosulfonyl group, m9h: 02, and (24) a 4- to 10-membered nitrogen-containing heterocycloalkylsulfonyl group which may be substituted by C.sub.1-8 alkyl group(s); R.sup.10 represents [1] a hydrogen atom, or [2] a 4- to 10-membered heterocycloalkyl group which may be substituted by 4- to 10-membered heterocycloalkyl group(s)].

6. A compound or salt or solvate thereof, which said compound is selected from the group consisting of: 9-(4-isopropyl-piperazin-1-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile; 6,6-dimethyl-8-(4-oxetan-3-yl-piperazin-1-yl)-11-oxo-9-prop-1-ynyl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile; 9-cyclopropylethynyl-6,6-dimethyl-8-(4-oxetan-3-yl-piperazin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile; 6,6-dimethyl-8-(1-oxetan-3-yl-piperidin-4-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile; 9-bromo-6,6-dimethyl-8-(4-oxetan-3-yl-piperazin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile; 9-bromo-8-(4-cyclopropyl-piperazin-1-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile; 9-chloro-6,6-dimethyl-8-(4-morpholin-4-yl-piperidin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile; 8-(4-cyclobutyl-piperazin-1-yl)-6,6-dimethyl-11-oxo-9-prop-1-ynyl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile; 6,6,9-trimethyl-8-(4-morpholin-4-yl-piperidin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile; 9-ethyl-6,6-dimethyl-8-(4-oxetan-3-yl-piperazin-1-yl)-1-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile; 9-ethyl-6,6-dimethyl-8-(4-morpholin-4-yl-piperidin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile; 9-ethynyl-6,6-dimethyl-8-(4-oxetan-3-yl-piperazin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile; 8-(4-cyclobutyl-piperazin-1-yl)-9-ethyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile; 9-ethynyl-6,6-dimethyl-11-oxo-8-(4-pyrrolidin-1-yl-piperidin-1-yl)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile; 6,6-dimethyl-11-oxo-8-(4-pyrrolidin-1-yl-piperidin-1-yl)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile; 8-(4-cyclobutyl-piperazin-1-yl)-9-ethynyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile; 8-(4-cyclobutyl-piperazin-1-yl)-6,6-dimethyl-11-oxo-9-propyl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile; 8-(1-isopropyl-piperidin-4-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile; 8-(4-isopropyl-piperazin-1-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile; 8-(4-cyclobutyl-piperazin-1-yl)-9-cyclopropyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile; 8-(2-tert-butylamino-ethoxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile; 9-ethynyl-8-(4-methanesulfonyl-piperazin-1-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile; 9-bromo-8-(4-cyclobutyl-piperazin-1-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile; 6,6-dimethyl-8-(4-oxetan-3-yl-piperazin-1-yl)-11-oxo-9-propyl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile; and 9-ethynyl-6,6-dimethyl-8-morpholin-4-yl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile.

7. A medicament comprising as an active ingredient the compound according to claim 1, or a salt or solvate thereof.

8. An ALK inhibitor comprising as an active ingredient the compound according to claim 1, or a salt or solvate thereof.

9. A pharmaceutical for the prophylaxis or treatment of cancer, cancer metastasis, depression or cognitive function disorder, comprising as an active ingredient the compound according to claim 1, or a salt or solvate thereof.

10. A pharmaceutical composition comprising the compound according to claim 1, or a salt or solvate thereof and a pharmaceutically acceptable carrier(s).

11. A method of treating or preventing cancer, cancer metastasis, depression or cognitive function disorder in a subject in need thereof comprising administering an effective amount of a pharmaceutical for the treatment of cancer, cancer metastasis, depression or cognitive function disorder, comprising as an active ingredient a compound represented by Formula (I): ##STR01235## wherein, A.sup.5 is selected from NR.sup.5, O and S; A.sup.4, A.sup.7, and A.sup.9 represent CR.sup.4, CR.sup.7, and CR.sup.9 respectively, or wherein A.sup.4 is N and A.sup.7 and A.sup.9 represent CR.sup.7 and CR.sup.9 respectively; R.sup.1 and R.sup.10 each independently represent [1] a hydrogen atom, [2] a cyano group, [3] a halogen atom or [4] a 4- to 10-membered heterocycloalkyl group which may be substituted by 4- to 10-membered heterocycloalkyl group(s); R.sup.2 is selected from the group consisting of: (1) a hydrogen atom, (2) a C.sub.1-8 alkyl group, (3) a C.sub.2-8 alkenyl group, (4) a C.sub.2-8 alkynyl group, (5) a cyano group, (6) a halogen atom, (7) a (C.sub.1-8 alkyl).sub.m2-amino group which may be substituted by C.sub.1-8 alkylsulfonyl group(s), m2: 02, and (8) a nitro group; R.sup.3 is selected from the group consisting of: (1) a hydrogen atom, (2) a C.sub.1-8 alkyl group which may be substituted by [1] halogen atom(s), [2]hydroxy group(s) or [3] C.sub.1-8 alkoxy group(s), (3) a C.sub.6-10 aryl group, (4) a cyano group, (5) a C.sub.1-8 alkanoyl group which may be substituted by C.sub.6-10 aryl group(s), (6) a (C.sub.1-8 alkyl).sub.m3a-aminocarbonyl group which may be substituted by one or more R.sup.3A, R.sup.3A: [1] a C.sub.6-10 aryl group, [2] a C.sub.1-8 alkoxy group, [3] a 5- to 14-membered heteroaryl group, or [4] a C.sub.6-10 arylsulfonyl group, m3a: 02, (7) a hydroxycarbonyl group, (8) a C.sub.1-8 alkoxycarbonyl group which may be substituted by [1] hydroxy group(s) or [2] C.sub.1-8 alkoxy group(s), (9) a halogen atom, (10) a (C.sub.1-8 alkyl).sub.m3b-amino group which may be substituted by C.sub.6-10 aryl group(s), m3b: 02, (11) a C.sub.1-8 alkylcarbonyl (C.sub.0-8 alkyl) amino group which may be substituted by [1]C.sub.6-10 aryl group(s) or [2] C.sub.6-10 aryloxy group(s), (12) a C.sub.6-10 arylcarbonyl (C.sub.0-8 alkyl) amino group which may be substituted by C.sub.1-8 alkyl group(s) which may be substituted by halogen atom(s), (13) a (C.sub.1-8 alkyl).sub.m3c-aminocarbonyl (C.sub.0-8 alkyl) amino group which may be substituted by C.sub.6-10 aryl group(s), m3c: 02, (14) a nitro group, (15) a hydroxy group, (16) a C.sub.1-8 alkoxy group which may be substituted by one or more R.sup.3B, R.sup.3B: [1] a hydroxy group, [2] a C.sub.1-8 alkoxy group, [3] a C.sub.6-10 aryl (C.sub.0-8 alkyl) aminocarbonyl group, [4] a (C.sub.1-8 alkyl).sub.m3d-amino group, or [5] a halogen atom, m3d: 02, (17) a 4- to 10-membered heterocycloalkyloxy group, (18) a 5- to 14-membered heteroaryloxy group, (19) a (C.sub.1-8 alkyl).sub.m3e-aminocarbonyloxy group which may be substituted by C.sub.6-10 aryl group(s) m3e: 02, (20) a 4- to 10-membered nitrogen-containing heterocycloalkylcarbonyl group, (21) a C.sub.1-8 alkylsulfonyloxy group which may be substituted by halogen atom(s), (22) a C.sub.1-8 alkylthio group, (23) a C.sub.1-8 alkylsulfonyl group which may be substituted by C.sub.6-10 aryl group(s), (24) a 5- to 14-membered heteroaryl group which may be substituted by C.sub.1-8 alkyl group(s) which may be substituted by C.sub.1-8 alkoxy group(s), (25) a C.sub.1-8 alkoxycarbonyl (C.sub.0-8 alkyl) amino group which may be substituted by C.sub.1-8 alkoxy group(s), (26) a C.sub.6-10 aryloxycarbonyl (C.sub.0-8 alkyl) amino group which may be substituted by C.sub.1-8 alkyl group(s) which may be substituted by halogen atom(s), (27) a C.sub.6-10 aryl (C.sub.0-8 alkyl) aminocarbonyl (C.sub.0-8 alkyl) amino group which may be substituted by one or more R.sup.3C, R.sup.3C: [1] a C.sub.1-8 alkyl group which may be substituted by halogen atom(s), or [2] a C.sub.1-8 alkoxy group, (28) a C.sub.3-8 cycloalkyl (C.sub.0-8 alkyl) aminocarbonyloxy group, and (29) a C.sub.6-10 aryl (C.sub.0-8 alkyl) aminocarbonyloxy group which may be substituted by substituent(s) selected from the group consisting of [1] a C.sub.1-8 alkyl group and [2] a C.sub.1-8 alkoxy group; R.sup.4 is selected from the group consisting of: (1) a hydrogen atom, (2) a C.sub.1-8 alkyl group which may be substituted by halogen atom(s), (3) a C.sub.2-8 alkenyl group, (4) a C.sub.2-8 alkynyl group, (5) a C.sub.3-8 cycloalkyl group, (6) a cyano group, (7) an aminocarbonyl group, (8) a (C.sub.1-8 alkyl).sub.m4a-aminocarbonyl group, m4a: 12, (9) a hydroxycarbonyl group, (10) a C.sub.1-8 alkoxycarbonyl group, (11) a halogen atom, (12) a (C.sub.1-8 alkyl).sub.m4b-amino group, m4b: 02, (13) a hydroxy group, and (14) a C.sub.1-8 alkoxy group which may be substituted by hydroxy group(s); R.sup.5 is selected from the group consisting of: (1) a hydrogen atom, (2) a C.sub.1-8 alkyl group which may be substituted by one or more R.sup.5A, R.sup.5A: [1] a hydroxycarbonyl group, [2] a C.sub.1-8 alkoxycarbonyl group, [3] a hydroxy group, [4] a C.sub.1-8 alkoxy group, [5] a (C.sub.1-8 alkyl).sub.m5-amino group, [6] a C.sub.6-10 aryl group, or [7] a C.sub.1-8 alkylthio group, m5: 02, (3) a C.sub.2-8 alkenyl group, (4) a C.sub.2-8 alkynyl group, (5) a C.sub.3-8 cycloalkyl group, and (6) a C.sub.1-8 alkylsulfonyl group; R.sup.6 and R.sup.6 are each independently selected from the group consisting of: (1) a C.sub.1-8 alkyl group which may be substituted by halogen atom(s), (2) a C.sub.2-8 alkenyl group, and (3) a C.sub.2-8 alkynyl group; or R.sup.6 and R.sup.6 are taken together with the carbon atoms to which they are bound to form: (4) a C.sub.3-8 cycloalkyl group, or (5) a 4- to 10-membered heterocycloalkyl group which may be substituted by C.sub.1-8 alkyl C.sub.6-10 aryl sulfonyl group(s) which may be substituted by C.sub.1-8 alkyl group(s); R.sup.7 is selected from the group consisting of: (1) a hydrogen atom, (2) a halogen atom, (3) a C.sub.1-8 alkoxy group which may be substituted by one or more R.sup.7A, R.sup.7A: [1] a (C.sub.1-8 alkyl).sub.m7a-amino group, [2] a hydroxy, [3] a 4- to 10-membered heterocycloalkyl group which may be substituted by C.sub.1-8 alkyl group(s), m7a: 02, (4) a C.sub.1-8 alkylsulfonyl group, (5) a nitro group, and (6) a hydroxyl group; R.sup.8 is selected from the group consisting of: (1) a hydrogen atom, (2) a C.sub.1-8 alkyl group which may be substituted by one or more RA, R.sup.8A: [1] a 4- to 10-membered heterocycloalkyl group which may be substituted by one or more R.sup.8A1, [2] a (C.sub.1-8 alkyl).sub.m8a-amino group which may be substituted by a halogen atom, or [3] a hydroxy group, m8a: 0-2, R.sup.8A1: [1] a C.sub.1-8 alkyl group, [2] a C.sub.1-8 alkylsulfonyl group, [3] a (C.sub.1-8 alkyl).sub.m8b-aminosulfonyl group, [4] an oxo group, [5] a C.sub.1-8 alkoxycarbonyl, or [6] a C.sub.1-8 alkoxycarbonyl (C.sub.0-8 alkyl) aminosulfonyl, m8b: 02, (3) a C.sub.2-8 alkenyl group, (4) a 4- to 10-membered heterocycloalkyl group which may be substituted by one or more R.sup.8B, R.sup.8B: <1> a C.sub.1-8 alkyl group which may be substituted by one or more R.sup.8B1, <2> a C.sub.2-8 alkeynyl group, <3> a C.sub.2-8 alkynyl group, <4> a C.sub.3-8 cycloalkyl group which may be substituted by [1] cyano group(s) or [2] C.sub.1-8 alkyl group(s), <5> a 4- to 10-membered heterocycloalkyl group which may be substituted by one or more R.sup.8B2, <6> a C.sub.1-8 alkoxy group which may be substituted by substituent(s) selected from the group consisting of [1] a C.sub.1-8 alkoxy group and [2] a C.sub.3-8 cycloalkyl group, <7> a C.sub.1-8 alkoxycarbonyl group, <8> a C.sub.1-8 alkylsulfonyl group, <9> a 5- to 14-membered heteroarylsulfonyl group, <10> an oxo group, <11> a cyano group, <12> a C.sub.1-8 alkanoyl group which may be substituted by one or more R.sup.8B3, <13> a C.sub.3-8 cycloalkylcarbonyl group, <14> a (C.sub.1-8 alkyl).sub.m8c-aminosulfonyl group, <15> a C.sub.1-8 alkylsulfonyl (C.sub.0-8 alkyl) amino group, <16> a (C.sub.1-8 alkyl).sub.m8d-amino group which may be substituted by one or more R.sup.8B4, <17> a hydroxy group, <18> a (C.sub.1-8 alkyl).sub.m8e-aminocarbonyl group, or <19> a C.sub.1-8 alkoxycarbonyl (C.sub.0-8 alkyl) amino group m8c: 02 m8d: 02 m8e: 02 R.sup.8B1: [1] a C.sub.3-8 cycloalkyl group, [2] a hydroxy group, or [3] a C.sub.1-8 alkoxy group(s), R.sup.8B2: [1] a halogen atom, [2] a C.sub.1-8 alkyl group, [3] an oxo group, [4] a hydroxy group, or [5] a deuterium atom, R.sup.8B3: a (C.sub.1-8 alkyl).sub.m8f-amino group, m8f: 02, R.sup.8B4: [1] a C.sub.3-8 cycloalkyl group, or [2] a hydroxy group, (5) a 5- to 14-membered heteroaryl group which may be substituted by a C.sub.1-8 alkyl group, (6) a (C.sub.1-8 alkyl).sub.m8g-aminocarbonyl group which may be substituted by one or more R.sup.8C, m8g: 02, R.sup.8C: [1] a hydroxy group, [2] a (C.sub.1-8 alkyl).sub.m8h-amino group which may be substituted by substituent(s) selected from the group consisting of <1> a (C.sub.1-8 alkyl).sub.m8i-aminosulfonyl group, <2> a C.sub.1-8 alkylsulfonyl group, <3> a C.sub.1-8 alkoxycarbonyl group and <4> a C.sub.1-8 alkoxycarbonyl(C.sub.0-8 alkyl) aminosulfonyl group, [3] a C.sub.1-8 alkylsulfonyl group, or [4] a C.sub.1-8 alkoxy group which may be substituted by a hydroxy group, m8h: 02, m8i: 02, (7) a 4- to 10-membered heterocycloalkyl (C.sub.0-8 alkyl) aminocarbonyl group which may be substituted by oxo group(s), (8) a 4- to 10-membered nitrogen-containing heterocycloalkylcarbonyl group which may be substituted by one or more R.sup.8D, R.sup.8D: [1] a C.sub.1-8 alkyl group which may be substituted by one or more R.sup.8D1, [2] a hydroxy group, [3] a C.sub.1-8 alkylsulfonyl group, or [4] a C.sub.1-8 alkoxycarbonyl group, R.sup.8D1: [1] a hydroxy group, or [2] a C.sub.1-8 alkoxy group, (9) a hydroxycarbonyl group, (10) a C.sub.0-8 alkoxy (C.sub.0-8 alkyl) aminocarbonyl group which may be substituted by hydroxy group(s), (11) a halogen atom, (12) a (C.sub.1-8 alkyl).sub.m8j-amino group which may be substituted by one or more R.sup.8H, m8j: 02, R.sup.8H: [1] a hydroxy group, or [2] a 4- to 10-membered heterocycloalkyl group, (13) a hydroxyl group, (14) a C.sub.1-8 alkoxy group which may be substituted by one or more R.sup.E, R.sup.8E: <1> a hydroxy group, <2> halogen atom, <3> a hydroxycarbonyl group, <4> a C.sub.1-8 alkoxycarbonyl group, <5> a 4- to 10-membered nitrogen-containing heterocycloalkylcarbonyl group which may be substituted by one or more R.sup.8E1, <6> a (C.sub.1-8 alkyl).sub.m8k1-amino group which may be substituted by one or more R.sup.8E2, m.sup.8k1: 02, <7> a 4- to 10-membered heterocycloalkyl group which may be substituted by one or more R.sup.8E3, <8> a 5- to 14-membered heteroaryl group, <9> a (C.sub.1-8 alkyl).sub.m8k2-aminocarbonyl group which may be substituted by one or more R.sup.8E6, m8k2: 02, <10> a C.sub.1-8 alkoxy group which may be substituted by one or more R.sup.8E7, <11> a C.sub.1-8 alkylthio group, <12> a C.sub.1-8 alkylsulfinyl group, <13> a C.sub.1-8 alkylsulfonyl group, R.sup.8E1: <1> a C.sub.1-8 alkoxycarbonyl group, <2> a C.sub.1-8 alkanoyl group, <3> a C.sub.1-8 alkylsulfonyl group, <4> a (C.sub.1-8 alkyl).sub.m8k3-aminosulfonyl group, m8k3: 02, or <5> a 4- to 10-membered heterocycloalkyl group, R.sup.8E2: <1> a hydroxy group, <2> a C.sub.1-8 alkoxycarbonyl group which may be substituted by halogen atom(s), <3> a C.sub.3-8 cycloalkyl group which may be substituted by C.sub.1-8 alkyl group(s) which may be substituted by hydroxy group(s), <4> a C.sub.1-8 alkanoyl group which may be substituted by substituent(s) selected from the group consisting of [1] a (C.sub.1-8 alkyl).sub.m8k4-amino group and [2] a halogen atom(s), m8k4: 02, <5> a (C.sub.1-8 alkyl).sub.m8k5-aminocarbonyl group, m8k5: 02, <6> a C.sub.1-8 alkylsulfonyl group, <7> a 4- to 10-membered nitrogen-containing heterocycloalkylsulfonyl group which may be substituted by C.sub.1-8 alkyl group(s), <8> a (C.sub.1-8 alkyl).sub.m8k6-aminosulfonyl group which may be substituted by C.sub.1-8 alkoxycarbonyl group(s), m8k6: 02, or R.sup.8E3: <1> a C.sub.1-8 alkyl group which may be substituted by substituent(s) selected from the group consisting of [1] a hydroxy group and [2] a C.sub.1-8 alkylcarbonyloxy group, <2> a C.sub.1-8 alkylcarbonyloxy group, <3> a hydroxy group, <4> a C.sub.3-8 cycloalkyl group, <5> a C.sub.1-8 alkoxy group, <6> a C.sub.1-8 alkoxycarbonyl group, <7> a C.sub.1-8 alkylsulfonyl group, <8> a (C.sub.1-8 alkyl).sub.m8k8-aminocarbonyl group m8k8: 02, <9> a C.sub.1-8 alkanoyl group which may be substituted by hydroxy group(s), <10> an oxo group, or <11> a 4- to 10-membered heterocycloalkyl group which may be substituted by substituent(s) selected from the group consisting of [1] a C.sub.1-8 alkanoyl group, [2] a C.sub.1-8 alkoxycarbonyl group and [3] a C.sub.1-8 alkylsulfonyl group, R.sup.8E6: <1> a C.sub.2-8 alkenylcarbonyloxy group, <2> a hydroxy group, <3> a cyano group, <4> a (C.sub.1-8 alkyl).sub.m8k9-amino group which may be substituted by hydroxy group(s) m8k9: 02, <5> a C.sub.1-8 alkoxy group which may be substituted by hydroxy group(s), <6> a C.sub.1-8 alkylcarbonyloxy group, <7> a 4- to 10-membered heterocycloalkyl group which may be substituted by C.sub.1-8 alkyl group(s), or <8> a 5- to 14-membered heteroaryl group, R.sup.8E7: <1> a hydroxy group, or <2> a C.sub.1-8 alkoxy group which may be substituted by hydroxy group(s), (15) a 4- to 10-membered heterocycloalkyloxy group which may be substituted by one or more R.sup.8F, R.sup.8F: <1> a C.sub.1-8 alkyl group which may be substituted by one or more R.sup.8F1, <2> a C.sub.3-8 cycloalkyl group, <3> a C.sub.1-8 alkanoyl group which may be substituted by halogen atom(s), <4> a C.sub.1-8 alkylcarbonyloxy group, <5> a C.sub.1-8 alkoxycarbonyl group, <6> a 4- to 10-membered heterocycloalkyl group which may be substituted by one or more R.sup.8F2, <7> a C.sub.1-8 alkyl sulfonyl group, <8> a hydroxy group, or [9] a C.sub.6-10 aryl group, R.sup.8F1: [1] a hydroxy group, [2] a C.sub.1-8 alkoxy group, or [3] a halogen atom, R.sup.8F2: [1] a 4- to 10-membered heterocycloalkyl group, [2] a C.sub.1-8 alkoxycarbonyl group, or [3] a C.sub.1-8 alkylsulfonyl group, (16) a 5- to 14-membered heteroaryloxy group, (17) a 4- to 10-membered heterocycloalkylcarbonyloxy group, (18) a (C.sub.1-8 alkyl).sub.m8l1-aminosulfonyloxy group, m8l1: 02, (19) a C.sub.1-8 alkyl thio group which may be substituted by [1] (C.sub.1-8 alkyl).sub.m8l2-amino group(s), [2] hydroxy group(s) or [3] hydroxycarbonyl group(s), m8l2: 02, (20) a C.sub.1-8 alkylsulfonyl group which may be substituted by one or more R.sup.8G, R.sup.8G: [1] a hydroxycarbonyl group, [2] a hydroxy group, or [3] a (C.sub.1-8 alkyl).sub.m8l3-amino group, m8l3: 02, (21) a 4- to 10-membered nitrogen-containing heterocycloalkylsulfonyloxy group which may be substituted by C.sub.1-8 alkyl group(s), (22) a C.sub.2-8 alkenyloxy group, and (23) a C.sub.1-8 alkylsulfonyloxy group which may be substituted by halogen atom(s); R.sup.9 is selected from the group consisting of: (1) a hydrogen atom, (2) a C.sub.1-8 alkyl group which may be substituted by one or more R.sup.9A, R.sup.9A: [1] a C.sub.3-8 cycloalkyl group, [2] a 4- to 10-membered heterocycloalkyl group which may be substituted by one or more R.sup.9A1, [3] a hydroxy group, [4] a C.sub.1-8 alkoxy group, or [5] a hydroxycarbonyl group, R.sup.9A1: [1] a C.sub.1-8 alkyl group, [2] a C.sub.3-8 cycloalkyl group, or [3] a 4- to 10-membered heterocycloalkyl group, (3) a C.sub.2-8 alkenyl group which may be substituted by one or more R.sup.9B, R.sup.9B: [1] a (C.sub.1-8 alkyl).sub.m9a-amino group, [2] a 4- to 10-membered heterocycloalkyl group which may be substituted by one or more group R.sup.9B1, R.sup.9B1: [1] a C.sub.3-8 cycloalkyl group, or [2] a 4- to 10-membered heterocycloalkyl group, m9a: 02, (4) a C.sub.2-8 alkynyl group which may be substituted by one or more R.sup.9C, R.sup.9C: [1] a C.sub.1-8 alkoxy group, [2] a (C.sub.1-8 alkyl).sub.m9b-amino group which may be substituted by C.sub.6-10 aryl group(s), [3] a 4- to 10-membered heterocycloalkyl group which may be substituted by one or more R.sup.9C1, [4] a C.sub.3-8 cycloalkyl group, [5] a hydroxy group, [6] a hydroxycarbonyl group, or [7] a C.sub.1-8 alkyloxycarbonyl group, m9b: 02, R.sup.9C1: [1] a C.sub.3-8 cycloalkyl group, [2] a 4- to 10-membered heterocycloalkyl group, or [3] an oxo group, (5) a C.sub.3-8 cycloalkyl group, (6) a 4- to 10-membered heterocycloalkyl group which may be substituted by one or more R.sup.9D, R.sup.9D: [1] a C.sub.1-8 alkyl group which may be substituted by 4- to 10-membered heterocycloalkyl group(s), [2] a C.sub.3-8 cycloalkyl group, [3] a 4- to 10-membered heterocycloalkyl group, or [4] a C.sub.1-6 alkylsulfonyl group, or [5] a C.sub.1-8 alkoxycarbonyl group, (7) a C.sub.6-10 aryl group which may be substituted by one or more R.sup.9E, R.sup.9E: [1] a halogen atom, [2] a hydroxy group, [3] a hydroxycarbonyl group, or [4] a C.sub.1-8 alkyl group which may be substituted by hydroxy group(s), or [5] a C.sub.1-8 alkoxy group, (8) a 5- to 14-membered heteroaryl group which may be substituted by C.sub.1-8 alkyl group(s), (9) a cyano group, (10) a C.sub.1-8 alkanoyl group, (11) a 4- to 10-membered nitrogen-containing heterocycloalkylcarbonyl group which may be substituted by C.sub.1-8 alkyl group(s), (12) a halogen atom, (13) a (C.sub.1-8 alkyl).sub.m9c-amino group which may be substituted by one or more R.sup.9F, m9c: 02, R.sup.9F: [9F-1] a C.sub.1-3 alkylsulfonyl group, [9F-2] a (C.sub.1-3 alkyl).sub.m9f1-aminosulfonyl group (m9f1: 02), or [9F-3] a C.sub.1-3 alkanoyl group which may be substituted by (C.sub.1-3 alkyl).sub.m9f2-amino group(s) (m9f2: 02), (14) a C.sub.1-8 alkylcarbonyl(C.sub.0-8 alkyl)amino group which may be substituted by (C.sub.1-8 alkyl).sub.m9d-amino group(s), m9d: 02, (15) a C.sub.1-8 alkylsulfonyl(C.sub.0-8 alkyl)amino group, (16) a (C.sub.1-8 alkyl).sub.m9e-aminosulfonyl(C.sub.0-8 alkyl)amino group, m9e: 02, (17) a nitro group, (18) a hydroxy group, (19) a C.sub.1-8 alkoxy group which may be substituted by one or more R.sup.9G, R.sup.9G: [1] a hydroxy group, [2] a hydroxycarbonyl group, [3] a C.sub.6-10 aryl group which may be substituted by C.sub.1-8 alkoxy group(s), [4] a (C.sub.1-8 alkyl).sub.m9g1-amino group, [5] a C.sub.1-8 alkoxy group which may be substituted by one or more R.sup.9G1, [6] a 5- to 14-membered heteroaryl group, or [7] a 4- to 10-membered heterocycloalkyloxy group which may be substituted by C.sub.1-8 alkyl group(s), m9g1: 02, R.sup.9G1: [1] a C.sub.1-8 alkoxy group, or [2] a hydroxycarbonyl group, (20) a 4- to 10-membered heterocycloalkyloxy group which may be substituted by [1] 4- to 10-membered heterocycloalkyl group(s), or [2] C.sub.1-8 alkoxycarbonyl group(s), (21) a C.sub.1-8 alkylsulfonyloxy group which may be substituted by halogen atom(s), (22) a C.sub.1-8 alkylthio group which may be substituted by (C.sub.1-8 alkyl).sub.m9f-amino group(s), m9f: 02, (23) a C.sub.1-8 alkylsulfonyl group which may be substituted by (C.sub.1-8 alkyl).sub.m9g-amino group(s), m9g: 02, (24) a (C.sub.1-8 alkyl).sub.m9h-aminosulfonyl group, m9h: 02, (25) a 4- to 10-membered nitrogen-containing heterocycloalkylsulfonyl group which may be substituted by C.sub.1-8 alkyl group(s), and (26) a hydroxycarbonyl group, or a salt or solvate thereof.

12. The method of claim 11, wherein the method comprises treating cancer or cancer metastasis in the subject in need thereof.

13. The method of claim 12, wherein the cancer is selected from the group consisting of lung cancer, anaplastic large cell lymphoma, inflammatory myofibroblastic tumor, esophageal cancer, and neuroblastoma.

14. The method of claim 11, wherein the method comprises treating depression or cognitive function disorder in the subject in need thereof.

15. The method of claim 11, wherein the pharmaceutical comprises as an active ingredient a compound selected from the group consisting of 9-(4-isopropyl-piperazin-1-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile; 6,6-dimethyl-8-(4-oxetan-3-yl-piperazin-1-yl)-11-oxo-9-prop-1-ynyl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile; 9-cyclopropylethynyl-6,6-dimethyl-8-(4-oxetan-3-yl-piperazin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile; 6,6-dimethyl-8-(1-oxetan-3-yl-piperidin-4-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile; 9-bromo-6,6-dimethyl-8-(4-oxetan-3-yl-piperazin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile; 9-bromo-8-(4-cyclopropyl-piperazin-1-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile; 9-chloro-6,6-dimethyl-8-(4-morpholin-4-yl-piperidin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile; 8-(4-cyclobutyl-piperazin-1-yl)-6,6-dimethyl-11-oxo-9-prop-1-ynyl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile; 6,6,9-trimethyl-8-(4-morpholin-4-yl-piperidin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile; 9-ethyl-6,6-dimethyl-8-(4-oxetan-3-yl-piperazin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile; 9-ethyl-6,6-dimethyl-8-(4-morpholin-4-yl-piperidin-1-yl)-1l-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile; 9-ethynyl-6,6-dimethyl-8-(4-oxetan-3-yl-piperazin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile; 8-(4-cyclobutyl-piperazin-1-yl)-9-ethyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile; 9-ethynyl-6,6-dimethyl-11-oxo-8-(4-pyrrolidin-1-yl-piperidin-1-yl)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile; 6,6-dimethyl-11-oxo-8-(4-pyrrolidin-1-yl-piperidin-1-yl)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile; 8-(4-cyclobutyl-piperazin-1-yl)-9-ethynyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile; 8-(4-cyclobutyl-piperazin-1-yl)-6,6-dimethyl-11-oxo-9-propyl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile; 8-(1-isopropyl-piperidin-4-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile; 8-(4-isopropyl-piperazin-1-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile; 8-(4-cyclobutyl-piperazin-1-yl)-9-cyclopropyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile; 8-(2-tert-butylamino-ethoxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile; 9-ethynyl-8-(4-methanesulfonyl-piperazin-1-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile; 9-bromo-8-(4-cyclobutyl-piperazin-1-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile; 6,6-dimethyl-8-(4-oxetan-3-yl-piperazin-1-yl)-11-oxo-9-propyl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile; and 9-ethynyl-6,6-dimethyl-8-morpholin-4-yl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile, or a salt or solvate thereof.

16. The method of claim 11, wherein the pharmaceutical comprises as an active ingredient 9-ethynyl-6,6-dimethyl-8-morpholin-4-yl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile, or a salt or solvate thereof.

Description

EXAMPLE

[0736] Hereinbelow, the present invention will be explained in greater detail in view of the following examples. However, the present invention is not limited by the examples.

NMR Analysis

[0737] NMR analysis was carried out by using JNM-EX270 (270 MHz, manufactured by JEOL), JNM-GSX400 (400 MHz, manufactured by JEOL), or 400 MR (400 MHz, manufactured by Varian). NMR data was expressed in ppm (parts per million; 6), while it was compared with the deuterium lock signal obtained from a sample solvent.

Mass Spectrum

[0738] The measurement was carried out by using JMS-DX303 or JMS-SX/SX102A (both manufactured by JEOL).

High Performance Liquid ChromatographyMass Spectrum Data (LC-MS)

[0739] Measurement was carried out by using Micromass (ZMD, manufactured by Micromass) equipped with 996-600E gradient high performance liquid chromatography (manufactured by Waters) or Micromass (ZQ, manufactured by Micromass) equipped with 2525 gradient high performance liquid chromatography (manufactured by Waters).

[0740] One of the following conditions that are described in the Table 1 below was taken as a condition for high performance liquid chromatography.

TABLE-US-00001 TABLE 1 Analysis Flow Rate Detection Condition Apparatus Column used Column Temperature Mobile phase, Gradient (mL/min) Wavelength A ZMD Cadenza CD-C18 35 deg. A) 0.05% TFA, H2O B) 0.05% 1.5 210-400 nm (Intakt) 3.0 mm I.D. TFA, MeCN PDA total 30 mm, 3 um (A/B): 95/5 => 0/100(3.5 min) => 0/100(1 min) B ZMD Cadenza CD-C18 35 deg. A) 0.05% TFA, H2O B) 0.05% 1.0 210-400 nm (Intakt) 3.0 mm I.D. TFA, MeCN PDA total 30 mm, 3 um (A/B): 95/5 => 0/100(9.5 min) => 0/100(2.5 min) C ZQ Chromolith Flash RP- Room Temp. A) 10 mM AcONH4, H2O B) MeOH 2.0 210-400 nm 18e (Merck KGaA) (A/B): 95/5 => 0/100(3 min) => PDA total 4.6 mm I.D. 25 mm 0/100(2 min) D ZQ Chromolith Flash RP- Room Temp. A) 10 mM AcONH4, H2O B) MeCN 2.0 210-400 nm 18e (Merck KGaA) (A/B): 95/5 => 0/100(3 min) => PDA total 4.6 mm I.D. 25 mm 0/100(2 min) F ZQ Cadenza CD-C18 35 deg. A) 0.05% TFA, H2O B) 0.05% 1.5 210-400 nm (Intakt) 3.0 mm I.D. TFA, MeCN PDA total 30 mm, 3 um (A/B): 95/5 => 0/100(3.5 min) => 0/100(1 min) H ZQ Cadenza CD-C18 35 deg. A) 0.05% TFA, H2O B) 0.05% 1.0 210-400 nm (Intakt) 3.0 mm I.D. TFA, MeCN PDA total 30 mm, 3 um (A/B): 95/5 => 0/100(9.5 min) => 0/100(2.5 min) I ZQ Ascentis Express C18 Room Temp. A) 10 mM AcONH4, H2O B) MeOH 1.0 210-400 nm (Sigma Aldrich) (A/B): 95/5 => 0/100(9.5 min) => PDA total 2.1 mm I.D. 50 mm 0/100(1 min) S ZQ Sunfire C18 (Waters) Room Temp. A) 0.05% TFA, H2O B) 0.05% 4.0 200-400 nm 4.5 mm I.D. 50 mm, 5 um TFA, MeCN PDA total (A/B): 90/10 => 5/95(3.5 min) => 90/10(1 min) => 90/10(0.5 min) T ZQ Sunfire C18 (Waters) Room Temp. A) 0.05% TFA, H2O B) 0.05% 4.0 200-400 nm 4.5 mm I.D. 50 mm, 5 um TFA, MeCN PDA total (A/B): 90/10 => 5/95(2 min) => 5/95(1.5 min) => 90/10(1.0 min) => 90/10(0.5 min) U ZQ WAKOsil 3C18 AR, (Wako Room Temp. A) 0.05% TFA, H2O B) 0.05% 2.0 210-400 nm Pure Chemical Industries, TFA, MeCN PDA total Ltd.) 4.6 mm I.D. 30 mm (A/B): 90/10 => 90/10(0.2 min) => 5/95(3.1 min) => 5/95(1.4 min) W ZMD Sunfire C18 (Waters) Room Temp. A) 0.05% TFA, H2O B) 0.05% 4.0 200-400 nm 4.5 mm I.D. 50 mm, 5 um TFA, MeCN PDA total (A/B): 90/10 => 5/95(3.5 min) => 90/10(1 min) => 90/10(0.5 min) Y ZMD Sunfire C18 (Waters) Room Temp. A) 0.05% TFA, H2O B) 0.05% 2.0 210-400 nm 4.5 mm I.D. 50 mm, 7 um TFA, MeCN PDA total (A/B): 90/10 => 0/100(3.5 min) => 0/100(1 min)

Microwave Reaction

[0741] The reaction was carried out by using a snap cap reaction vial together with an Explorer (manufactured by CEM Microwave Technology) or an initiator (manufactured by Biotage). Maximum output setting includes cooling of the reaction vessel by air in order to avoid temperature increase caused by microwave irradiation.

[0742] Commercially available reagents were obtained and used without any further purification. The room temperature indicates the temperature range of between about 20 to 25 C. All the non-aqueous reaction was carried out in anhydrous solvent under nitrogen or argon atmosphere. For concentration under reduced pressure or removal of a solvent by distillation, a rotary evaporator was used.

[0743] For preparing the compounds, when there is a possibility of having an undesirable side reaction, a functional group was protected using a protecting group to produce a target molecule, and the protecting group was removed later, if desired. Selection, addition and removal of a protecting group were carried out according to the method described in the literature [Greene and Wuts, Protective Groups in Organic Synthesis (4.sup.th edition, John Wiley & Sons 2007)], for example.

Example 1

Compound A2

7-Methoxy-1,1-dimethyl-3,4-dihydro-1H-naphthalen-2-one

[0744] ##STR00016##

[0745] 7-Methoxy-3,4-dihydro-1H-naphthalen-2-one (Compound A1, 209 g, 1.18 mol), tetrabutylammonium hydrogen sulfate (40 g, 0.118 mol) and methyl iodide (162 g, 2.60 mol) were suspended in THF (500 ml) at room temperature. Under stirring, the mixture was added with 50% aqueous solution of potassium hydroxide (400 g) over 5 min. Reflux occurred as the inner temperature rapidly increases. Once the inner temperature stopped to increase, stirring was continued for 45 min. The reaction solution was diluted with distilled water (1 L) and extracted twice with CPME (1.5 L). The combined organic layer was washed (distilled water 1 L3), dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting crude product was recrystallized with MeOH (1 L) and distilled water (500 ml) to obtain the title compound as a colorless needle-like crystal (177 g, 73%).

[0746] .sup.1H-NMR (400 MHz, CDCl.sub.3) 1.43 (6H, s), 2.65 (2H, t, 12 Hz), 3.02 (2H, t, 12 Hz), 3.79 (3H, s), 6.74 (1H, m), 6.87 (1H, m), 7.24 (1H, m).

[0747] LCMS: m/z 205 [M+H].sup.+

Example 2

Compound A3-1, Compound A3-2

3-Bromo-8-methoxy-6,6-dimethyl-6,11-dihydro-5H-benzo[b]carbazole

1-Bromo-8-methoxy-6,6-dimethyl-6,11-dihydro-5H-benzo[b]carbazole

[0748] ##STR00017##

[0749] 7-Methoxy-1,1-dimethyl-3,4-dihydro-1H-naphthalen-2-one (Compound A2, 66.2 g, 324 mmol) and 3-bromophenylhydrazine hydrochloric acid salt (71.0 g, 318 mmol) were dissolved in AcOH (350 ml) and refluxed under stirring for 6 hr. The reaction solvent was removed by distillation under reduced pressure to obtain the crude product as a mixture of the title compound A3-1 and A3-2.

Example 3

Compound A4

3-Bromo-8-methoxy-6,6-dimethyl-5,6-dihydrobenzo[b]carbazol-11-one

[0750] ##STR00018##

[0751] The crude product obtained from the above (i.e., mixture of A3-1 and A3-2) was dissolved in a mixture solvent of THF (450 ml) and distilled water (50 ml), added once with DDQ (115 g, 509 mmol), and then stirred at room temperature for 1 hr. The reaction mixture was diluted with CPME 3L, and the organic layer was washed three times with 0.5 N aqueous solution of sodium hydroxide (1 L) and twice with distilled water (1 L) in order and dried over anhydrous sodium sulfate. The organic layer was concentrated to 500 ml under reduced pressure. The precipitated product was collected by filtration and washed with a small amount of CPME to obtain the title compound as a yellow crystal (48 g, 40%).

[0752] .sup.1H-NMR (400 MHz, DMSO-d.sub.6) : 1.73 (6H, s), 3.90 (3H, s), 7.06-7.09 (1H, m), 7.32-7.38 (2H, m), 7.65-7.66 (1H, m), 8.09-8.17 (2H, m), 12.32 (1H, br. s).

[0753] LCMS: m/z 370, 372 [M+H].sup.+

Example 4

Compound AA1

4-Methoxy-2-(3-trimethylsilanylprop-2-ynyl)-benzoic Acid Methyl Ester

[0754] ##STR00019##

[0755] To the THF (16 ml) solution of 2-bromomethyl-4-methoxy-benzoic acid methyl ester (961 mg, 4.09 mmol), triphenylphosphine (107 mg, 0.1 eq.), cesium carbonate (1.87 g, 1.4 eq.), copper iodide (59 mg, 0.076 eq.) and tris (dibenzylideneacetone) dipalladium (86 mg, 0.023 eq.) were added, degassed, flushed with nitrogen gas, added with trimethylsilylacetylene (734 l, 1.3 eq.), and then stirred overnight at 55 C. To the reaction solution, saturated aqueous solution of ammonium chloride was added followed by extraction with ethyl acetate. The organic layer was washed with brine and dried over magnesium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain the title compound (brown oily substance, 606 mg, 54%).

[0756] .sup.1H-NMR (400 MHz, CDCl.sub.3) : 7.93 (1H, d, J=8.8 Hz), 7.33 (1H, d, J=2.6 Hz), 6.78 (1H, dd, J=8.8, 2.6 Hz), 4.09 (2H, s), 3.86 (3H, s), 3.84 (3H, s), 0.14 (9H, s).

[0757] LCMS: m/z 277 [M+H].sup.+

[0758] HPLC retention time: 3.30 min (analysis condition U)

Example 5

Compound AA2

2-(1,1-Dimethyl-3-trimethylsilanylprop-2-ynyl)-4-methoxy-benzoic Acid Methyl Ester

[0759] ##STR00020##

[0760] To the toluene (4 ml) solution of 4-methoxy-2-(3-trimethylsilanyl-prop-2-ynyl)-benzoic acid methyl ester (Compound AA1, 273 mg, 0.988 mmol), sodium bis (trimethylsilyl) amide (2.1 ml, 1.9 m solution, 4 eq.) and iodomethane (308 l, 5 eq.) were added at 78 C. After allowing the reaction temperature to increase to the room temperature, the mixture was stirred for 2 hr. To the reaction solution, saturated aqueous solution of ammonium chloride was added followed by extraction with ethyl acetate. The organic layer was washed with brine and dried over magnesium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain the title compound (yellow oily substance, 226 mg, 75%).

[0761] .sup.1H-NMR (400 MHz, CDCl.sub.3) : 7.45 (1.0H, d, J=8.4 Hz), 7.09 (1.1H, d, J=2.6 Hz), 6.75 (1H, m), 3.84 (3H, s), 3.82 (3H, s), 1.70 (6H, s), 0.14 (9H, s)

[0762] LCMS: m/z 305 [M+H].sup.+

[0763] HPLC retention time: 3.38 min (analysis condition U)

Example 6

Compound AA3

2-(1,1-Dimethylprop-2-ynyl)-4-methoxy-benzoic Acid Methyl Ester

[0764] ##STR00021##

[0765] To the THF (18 ml) solution of 2-(1,1-dimethyl-3-trimethylsilanylprop-2-ynyl)-4-methoxy-benzoic acid methyl ester (Compound AA2, 912 mg, 3 mmol), tetrabutylammonium fluoride (2.061 g, 2.6 eq.) was added, and then stirred for 3 hr at room temperature. To the reaction solution, saturated aqueous solution of ammonium chloride was added followed by extraction with ethyl acetate. The organic layer was washed with brine and dried over magnesium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain the title compound (yellow oily substance, 524 mg, 75%).

[0766] .sup.1H-NMR (400 MHz, CDCl.sub.3) : 7.44 (1H, d, J=8.4 Hz), 7.05 (1H, d, J=2.3 Hz), 6.76 (1H, dd, J=8.4, 2.3 Hz), 3.84 (3H, s), 3.82 (3H, s), 1.73 (6H, s)

[0767] LCMS: m/z 223 [M+H].sup.+

[0768] HPLC retention time: 2.55 min (analysis condition U)

Example 7

Compound AA4

2-[1-(6-Cyano-1-methanesulfonyl-1H-indol-2-yl)-1methylethyl]-4-methoxy-benzoic Acid Methyl Ester

[0769] ##STR00022##

[0770] To the DMF (2 ml) solution of 2-(1,1-dimethylprop-2-ynyl)-4-methoxy-benzoic acid methyl ester (Compound AA3, 134 mg, 0.577 mmol) and N-(2-bromo-5-cyanophenyl)methanesulfonamide (Compound AA5, 167 mg, 1.05 eq.), copper iodide (9 mg, 0.08 eq.) and TEA (129 l, 1.6 eq.) were added, degassed and flushed with nitrogen gas, added with dicholorobis (triphenylphosphine) palladium (20 mg, 0.05 eq.), and then degassed and flushed again with nitrogen gas. After stirring for 2 hr at 90 C., the reaction solution was added with water, extracted with ethyl acetate. The organic layer was washed with an brine and dried over magnesium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain the title compound (white solid, 152 mg, 62%).

[0771] .sup.1H-NMR (400 MHz, DMSO-d.sub.6) : 8.19 (1H, dd, J=0.6, 0.6 Hz), 7.84 (1H, dd, J=8.0, 0.6 Hz), 7.67 (1H, dd, J=8.0, 1.3 Hz), 7.13 (1H, d, J=8.4 Hz), 6.99 (1H, s), 6.96 (1H, br. s), 6.85 (1H, dd, J=8.4, 2.5 Hz), 3.78 (3H, s), 3.12 (3H, s), 3.09 (3H, br. s), 1.89 (6H, s).

[0772] LCMS: m/z 427 [M+H].sup.+

[0773] HPLC retention time: 2.77 min (analysis condition U)

Example 8

Compound AA5

N-(2-Bromo-5-cyanophenyl)methanesulfonamide

[0774] ##STR00023##

[0775] To a mixture of 3-amino-4-bromo-benzonitrile (1.98 g, 10 mmol), TEA (5.06 g, 50 mmol), and methylene chloride (50 ml), mesyl chloride (2.71 ml, 35 mmol) was added at 0 C. and the mixture was stirred at room temperature for 30 min. Water was added to the reaction solution, which was then extracted with dichloromethane. The organic layer was dried over sodium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were added with tetrahydrofuran (100 ml), water (400 l) and sodium hydride (540 mg, 15.5 mmol), and stirred at room temperature for 16 hr. To the reaction solution, saturated aqueous solution of ammonium chloride (200 ml) was added followed by extraction with ethyl acetate. The organic layer was dried over sodium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (hexane/ethyl acetate) to obtain the title compound (2.48 g, 90%).

[0776] .sup.1H-NMR (400 MHz, DMSO-d.sub.6) : 9.82 (1H, s), 7.87 (1H, d, J=4 Hz), 7.75 (1H, d, J=8 Hz), 7.70 (1H, dd, J=8 Hz, 4 Hz), 3.14 (3H, s)

[0777] HPLC retention time: 1.63 min (analysis condition U)

Example 9

Compound AA6

2-(1-Hydroxy-1-methylethyl)-1H-indole-6-carbonitrile

[0778] ##STR00024##

[0779] To N-(2-bromo-5-cyanophenyl)methanesulfonamide (Compound AA5, 230 mg, 1 mmol), 3-methyl-2-butyn-3-ol (0.15 ml, 1.5 mmol), X-Phos (72 mg, 15% mol), PdCl.sub.2(CH.sub.3CN).sub.2 (13 mg, 5% mol) and cesium carbonate (390 mg, 2 mmol), DMA (2 ml) was added, and the mixture was stirred at 100 C. for 3 hr. Water and 5 N hydrochloric acid solution were added to the reaction solution, which was then extracted with ethyl acetate. The organic layer was dried over sodium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (hexane/ethyl acetate) to obtain the title compound (130 mg, 75%).

[0780] .sup.1H-NMR (400 MHz, CDCl.sub.3) : 8.76 (1H, s), 7.68 (1H, s), 7.60 (1H, d, J=8 Hz), 7.32 (1H, dd, J=8 Hz, 4 Hz), 6.37 (1H, m), 1.93 (1H, s), 1.70 (6H, s)

[0781] LCMS: m/z 201 [M+H].sup.+

[0782] HPLC retention time: 2.12 min (analysis condition U)

Example 10

Compound A5-1

3-Bromo-8-hydroxy-6,6-dimethyl-5,6-dihydrobenzo[b]carbazol-11-one

[0783] ##STR00025##

[0784] Under the same conditions as the method for synthesizing Compound A6, the title compound was synthesized from Compound A4.

[0785] .sup.1H-NMR (400 MHz, DMSO-d.sub.6) : 12.30 (1H, s), 10.21 (1H, s), 8.06-8.11 (1H, m), 8.01-8.05 (1H, m), 7.62-7.66 (1H, m), 7.32-7.37 (1H, m), 7.08-7.12 (1H, m), 6.84-6.90 (1H, m), 1.69 (6H, s).

[0786] LCMS: m/z 356, 358 [M+H].sup.+

[0787] HPLC retention time: 2.30 min (analysis condition U)

Example 11

Compound A5-2

8-Methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[0788] ##STR00026##

[0789] (Method 1) 3-Bromo-8-methoxy-6,6-dimethyl-5,6-dihydrobenzo[b]carbazol-11-one (Compound A4, 10.45 g, 28.2 mmol) and copper (I) cyanide (5.0 g, 50.2 mmol) were dissolved in NMP (100 ml), followed by stirring at 170 C. for 17 hr. The reaction mixture was suspended in ethyl acetate (500 mL) and distilled water (200 mL). The insoluble matters were removed by Celite filtration and washed twice with ethyl acetate (300 mL2). The organic layer was washed once with an aqueous solution of disodium EDTA (200 mL) and twice with saturated brine (200 mL) in order, and dried over anhydrous sodium sulfate. The organic layer was concentrated under reduced pressure to yield a product, which was suspended and washed with a small amount of CPME to obtain the title compound as a colorless crystal (6.58 g, 73%).

[0790] (Method 2) To the THF (5.6 ml) solution of 2-[1-(6-cyano-1-methanesulfonyl-1H-indol-2-yl)-1-methylethyl]-4-methoxy-benzoic acid methyl ester (Compound AA4, 138 mg, 0.324 mmol), tetrabutylammonium fluoride (514 mg, 6 eq.) was added, and the mixture was stirred at room temperature overnight. Thereafter, 2 M aqueous solution of sodium hydroxide (5.6 ml) was added to the mixture, which was then stirred for 4 hr, added with 1 M HCl, and extracted with ethyl acetate. The organic layer was washed with brine and dried over magnesium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were dissolved in ethyl acetate (10 ml) and added with e 4 M HCl and ethyl acetate solution (10 ml) followed by stirring at room temperature for 30 min. The residues obtained after concentration of the reaction solution under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain the title compound (89.2 mg, 62%).

[0791] (Method 3) To nitrobenzene (5 ml) and aluminum chloride (400 mg, 3 mmol), 4-methoxybenzoyl chloride (400 mg, 2.3 mmol) was added. After stirring for 30 min at room temperature, 2-(1-hydroxy-1-methyl-ethyl)-1H-indole-6-carbonitrile (Compound AA6, 200 mg, 1 mmol) was added followed by stirring at room temperature for 3 hr. Water was added to the reaction solution, which was then extracted with ethyl acetate. The organic layer was dried over sodium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (hexane/ethyl acetate) to obtain the title compound (127 mg, 40%).

[0792] .sup.1H-NMR (400 MHz, DMSO-d.sub.6) : 1.71 (6H, s), 3.89 (3H, s), 7.07-7.09 (1H, m), 7.34 (1H, s), 7.58-7.60 (1H, m), 7.99 (1H, s), 8.14-8.16 (1H, m), 8.30-8.32 (1H, m), 12.32 (1H, br. s),

[0793] LCMS: m/z 317 [M+H].sup.+

[0794] HPLC retention time: 2.56 min (analysis condition U)

Example 12

Compound A6

8-Hydroxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[0795] ##STR00027##

[0796] 8-Methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (Compound A5-2, 6.58 g, 20.8 mmol) was dissolved in pyridine hydrochloric acid salt (25.0 g), and stirred at 170 C. for 13 hr. The reaction mixture was partitioned in ethyl acetate (400 mL) and distilled water (400 mL), and the aqueous layer was extracted one more time with ethyl acetate (400 mL). The combined organic layer was washed twice with distilled water (100 mL) and once with saturated brine (100 mL) in order, and dried over anhydrous sodium sulfate. The organic layer was concentrated under reduced pressure to yield a product, which was suspended and washed with a small amount of CPME to obtain the title compound as a colorless crystal (5.91 g, 93%).

[0797] .sup.1H-NMR (400 MHz, DMSO-d.sub.6) : 1.73 (6H, s), 6.87-6.90 (1H, m), 7.11 (1H, s), 7.57-7.59 (1H, m), 7.97 (1H, s), 8.04-8.06 (1H, m), 8.29-8.31 (1H, m), 10.27 (1H, s), 12.66 (1H, br. s),

[0798] LCMS: m/z 303 [M+H].sup.+

Example 13

Compound A7-1

4-(3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yloxy)-piperidine-1-carboxylic Acid Tert-Butyl Ester

[0799] ##STR00028##

[0800] 8-Hydroxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (Compound A6, 30 mg, 0.099 mmol) was dissolved in THF (1 mL), added with 4-hydroxy-piperidine-1-carboxylic acid tert-butyl ester (40 mg, 2 eq.), triphenylphosphine (52 mg, 2 eq.), and diisopropyl azodicarboxlyate (43 L, 2 eq.) in order, and stirred at room temperature for 4 hr. The reaction solution was poured to water, and then extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over sodium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain the title compound (37 mg, 76%).

[0801] .sup.1H-NMR (400 MHz, CDCl.sub.3) : 9.44 (1H, s), 8.77 (1H, d, J=7.8 Hz), 8.62 (1H, d, J=8.2 Hz), 8.00 (1H, s), 7.81 (1H, d, J=8.2 Hz), 7.34 (1H, s), 7.26 (1H, d, J=7.8 Hz), 4.85-4.93 (1H, m), 3.96-4.04 (2H, m), 3.60-3.70 (2H, m), 2.19-2.32 (2H, m), 1.89-2.15 (8H, m), 1.74 (9H, s)

[0802] LCMS: m/z 430 [M+H].sup.+

[0803] HPLC retention time: 4.09 min (analysis condition W)

Example 14

Compound A7-2

6,6-Dimethyl-11-oxo-8-[2-(2-oxo-imidazolidin-1-yl)-ethoxy]-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[0804] ##STR00029##

[0805] Under the same conditions as the method for synthesizing Compound A7-1, the title compound was prepared from Compound A6 and 1-(2-hydroxy-ethyl)-imidazolidin-2-one.

[0806] LCMS: m/z 415 [M+H].sup.+

[0807] HPLC retention time: 2.96 min (analysis condition W)

Example 15

Compound A7-3

[2-(3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yloxy)-ethyl]-carbamic Acid Tert-Butyl Ester

[0808] ##STR00030##

[0809] Under the same conditions as the method for synthesizing Compound A7-1, the title compound was prepared from Compound A6 and (2-hydroxy-ethyl)-carbamic acid tert-butyl ester.

[0810] LCMS: m/z 346 [M+H].sup.+

[0811] HPLC retention time: 2.40 min (analysis condition W)

Example 16

Compound A7-4

6,6-Dimethyl-8-(2-methylsulfanyl-ethoxy)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[0812] ##STR00031##

[0813] Under the same conditions as the method for synthesizing Compound A7-1, the title compound was prepared from Compound A6 and 2-methylthioethanol.

[0814] LCMS: m/z 451 [M+H].sup.+

[0815] HPLC retention time: 4.23 min (analysis condition W)

Example 17

Compound A7-5

6,6-Dimethyl-8-(2-methylsulfanyl-ethoxy)-5-(2-methylsulfanyl-ethyl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[0816] ##STR00032##

[0817] The title compound was obtained as a by-product of the synthesis of Compound A7-4.

[0818] LCMS: m/z 377 [M+H].sup.+

[0819] HPLC retention time: 3.75 min (analysis condition W)

Example 18

Compound A7-6

6,6-Dimethyl-11-oxo-8-(tetrahydro-pyran-4-yloxy)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[0820] ##STR00033##

[0821] Under the same conditions as the method for synthesizing Compound A7-1, the title compound was prepared from Compound A6 and tetrahydropyran-4-ol.

[0822] .sup.1H-NMR (400 MHz, DMSO-d.sub.6) : 12.72 (1H, br. s), 8.32 (1H, d, 8.5 H z), 8.15 (1H, d, 8.5 Hz), 8.01 (1H, s), 7.61 (1H, d, 8.5 Hz), 7.38 (1H, s), 7.15 (1H, d, 8.5 Hz), 4.86-4.81 (1H, m), 3.93-3.88 (2H, m), 3.58-3.52 (2H, m), 2.06-2.00 (2H, m), 1.85 (6H, s), 1.69-1.60 (2H, m)

[0823] LCMS: m/z 387 [M+H].sup.+

[0824] HPLC retention time: 3.47 min (analysis condition W)

Example 19

Compound A7-7

6,6-Dimethyl-11-oxo-8-(pyridin-4-ylmethoxy)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[0825] ##STR00034##

[0826] Under the same conditions as the method for synthesizing Compound A7-1, the title compound was prepared from Compound A6 and pyridin-4-yl-methanol.

[0827] LCMS: m/z 394 [M+H].sup.+

[0828] HPLC retention time: 2.56 min (analysis condition W)

Example 20

Compound A7-8

8-(2-Methoxyethoxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[0829] ##STR00035##

[0830] Under the same conditions as the method for synthesizing Compound A7-1, the title compound was prepared from Compound A6 and 2-methoxyethanol.

[0831] .sup.1H-NMR (400 MHz, DMSO-d.sub.6) : 11.69 (1H, br. s), 8.27 (1H, d, 7.9 Hz), 8.10 (1H, d, 8.5 Hz), 7.95 (1H, s), 7.55 (1H, d, 7.9 Hz), 7.32 (1H, d, 2.4 Hz), 7.05 (1 H, d, 8.5 Hz), 4.22 (2H, t, 4.3 Hz), 3.67 (2H, t, 4.3 Hz), 1.72 (6H, s)

[0832] LCMS: m/z 361 [M+H].sup.+

[0833] HPLC retention time: 3.38 min (analysis condition W)

Example 21

Compound A7-9

8-[2-(2-Methoxyethoxy)ethoxy]-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[0834] ##STR00036##

[0835] Under the same conditions as the method for synthesizing Compound A7-1, the title compound was prepared from Compound A6 and 2-(2-methoxyethoxy)ethanol.

[0836] LCMS: m/z 405 [M+H].sup.+

[0837] HPLC retention time: 3.32 min (analysis condition W)

Example 22

Compound A7-10

6,6-Dimethyl-8-(3-methyloxetan-3-ylmethoxy)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[0838] ##STR00037##

[0839] Under the same conditions as the method for synthesizing Compound A7-17, the title compound was prepared from Compound A6 and 3-chloromethyl-3-methyloxetane.

[0840] LCMS: m/z 387 [M+H].sup.+

[0841] HPLC retention time: 2.23 min (analysis condition S)

Example 23

Compound A7-11-1

[2-(3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yloxy)ethyl] ethyl-carbamic Acid Tert-Butyl Ester

[0842] ##STR00038##

[0843] Under the same conditions as the method for synthesizing Compound A7-1, the title compound was prepared from Compound A6 and ethyl-(2-hydroxy-ethyl)-carbamic acid tert-butyl ester.

[0844] LCMS: m/z 474 [M+H].sup.+

[0845] HPLC retention time: 2.93 min (analysis condition U)

Example 24

Compound A7-11-2

8-(2-Ethylaminoethoxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[0846] ##STR00039##

[0847] Under the same conditions as the method for synthesizing Compound A8-1, the title compound was prepared from Compound A7-11-1.

[0848] LCMS: m/z 374 [M+H].sup.+

[0849] HPLC retention time: 1.35 min (analysis condition U)

Example 25

Compound A7-12

8-(2-Hydroxyethoxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[0850] ##STR00040##

[0851] Under the same conditions as the method for synthesizing Compound A7-17, the title compound was prepared from Compound A6 and 2-bromo-ethanol.

[0852] LCMS: m/z 437 [M+H].sup.+

[0853] HPLC retention time: 2.93 min (analysis condition U)

Example 26

Compound A7-13-1

6,6-Dimethyl-11-oxo-8-(2-phenyl-[1,3]dioxan-5-yloxy)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[0854] ##STR00041##

[0855] Under the same conditions as the method for synthesizing Compound A7-1, the title compound was prepared from Compound A6 and 2-phenyl-[1,3]dioxan-5-ol.

[0856] LCMS: m/z 465 [M+H].sup.+

[0857] HPLC retention time: 4.10 min (analysis condition W)

Example 27

Compound A7-13-2

8-(2-Hydroxy-1-hydroxymethylethoxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[0858] ##STR00042##

[0859] Anhydrous ferric trichloride (56 mg, 5 eq.) was added to the dichloromethane (2 mL) suspension of 6,6-dimethyl-11-oxo-8-(2-phenyl-[1,3]dioxan-5-yloxy)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (Compound A7-13-1, 13 mg, 0.028 mmol), and stirred at room temperature for 1 hr. The reaction solution was added to water, and then extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over sodium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were purified by high performance liquid chromatography to obtain the title compound (7 mg, 46%).

[0860] LCMS: m/z 377 [M+H].sup.+

[0861] HPLC retention time: 2.70 min (analysis condition W)

Example 28

Compound A7-14-1

8-((S)-2,2-Dimethyl-[1,3]dioxolan-4-ylmethoxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[0862] ##STR00043##

[0863] Under the same conditions as the method for synthesizing Compound A7-17, the title compound was prepared from Compound A6 and toluene-4-sulfonic acid (R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethyl ester.

[0864] LCMS: m/z 417 [M+H].sup.+

[0865] HPLC retention time: 3.47 min (analysis condition Y)

Example 29

Compound A7-14-2

8-((R)-2,3-Dihydroxy-propoxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[0866] ##STR00044##

[0867] To the solution of THF and water (4:1, 1 mL) of 8-(2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (Compound A14-1, 30 mg, 0.07 mmol), camphor sulfonic acid (36 mg, 0.14 mmol) was added at room temperature. After stirring at room temperature for 38 hr, the mixture was extracted with ethyl acetate. The organic layer was dried over sodium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (dichloromethane/methanol) to obtain the title compound (white solid, 28 mg, 72%).

[0868] .sup.1H-NMR (300 MHz, DMSO-d.sub.6) ppm; 12.7 (s, 1H), 8.31 (d, 1H, J=8.01 Hz), 8.15 (d, 1H, J=8.77 Hz), 8.00 (s, 1H), 7.60 (d, 1H, J=8.01 Hz), 7.12 (s, 1H), 7.09 (d, 1H, J=8.77 Hz), 4.46 (m, 1H), 4.15 (m, 3H), 3.78 (m, 1H), 1.76 (s, 6H), 1.38 (s, 3H), 1.32 (s, 3H)

[0869] LCMS: m/z 377 [M+H].sup.+

[0870] HPLC retention time: 1.80 min (analysis condition U)

Example 30

Compound A7-14-3

8-((S)-2,2-Dimethyl-[1,3]dioxolan-4-ylmethoxy)-5,6,6-trimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[0871] ##STR00045##

[0872] Under the same conditions as the method for synthesizing Compound B3-4, the title compound was prepared as a crude product from Compound A7-14-1.

Example 31

Compound A7-14-4

8-((R)-2,3-Dihydroxy-propoxy)-5,6,6-trimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[0873] ##STR00046##

[0874] Under the same conditions as the method for synthesizing Compound A7-14-2, the title compound was prepared from Compound A7-14-3 (303 mg, 98%).

[0875] LCMS: m/z 484 [M+H].sup.+

[0876] HPLC retention time: 2.08 min (analysis condition D)

Example 32

Compound A7-15-1

8-[(4R,5S)-5-(Tert-butyl-dimethyl-silanyloxymethyl)-2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy]-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[0877] ##STR00047##

[0878] Under the same conditions as the method for synthesizing Compound A7-1, the title compound was prepared from Compound A6 and [(4R,5R)-5-(tert-butyl-dimethyl-silanyloxymethyl)-2,2-dimethyl-[1,3]dioxolan-4-yl]-methanol.

[0879] LCMS: m/z 516 [M+H].sup.+

[0880] HPLC retention time: 3.97 min (analysis condition Y)

Example 33

Compound A7-15-2

6,6-Dimethyl-11-oxo-8-((2R,3R)-2,3,4-trihydroxy-butoxy)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[0881] ##STR00048##

[0882] Under the same conditions as the method for synthesizing Compound A7-14-2, the title compound was prepared from Compound A7-15-1.

[0883] LCMS: m/z 407 [M+H].sup.+

[0884] HPLC retention time: 1.73 min (analysis condition U)

Example 34

Compound A7-16

6,6-Dimethyl-8-(1-methyl-piperidin-4-yloxy)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[0885] ##STR00049##

[0886] Under the same conditions as the method for synthesizing Compound A7-1, the title compound was prepared from Compound A6 and 1-methylpiperidin-4-ol.

[0887] .sup.1H-NMR (400 MHz, DMSO-d.sub.6) : 12.75 (1H, s), 8.32 (1H, d, J=7.9 Hz), 8.14 (1H, d, J=9.8 Hz), 8.00 (1H, s), 7.60 (1H, d, J=7.9 Hz), 7.34 (1H, s), 7.11 (1H, d, J=9.1 Hz), 4.62 (1H, m), 2.64 (2H, m), 2.23 (2H, m), 2.21 (s, 3H), 1.99 (2H, m), 1.77 (s, 6H), 1.73 (2H, m).

[0888] LCMS: m/z 400 [M+H].sup.+

[0889] HPLC retention time: 1.42 min (analysis condition S)

Example 35

Compound A7-17

8-(2-Diethylamino-ethoxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[0890] ##STR00050##

[0891] 8-Hydroxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (Compound A6, 25 mg, 0.083 mmol) was dissolved in N,N-dimethylacetamide (1 mL), added with 2-chloroethyldiethylamine (16 mg, 1.1 eq.) and cesium carbonate (54 mg, 2 eq.) in order and stirred at 100 C. for 4 hr. The reaction solution was poured over water and extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over sodium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were purified by amino silica gel column chromatography (ethyl acetate/hexane) to obtain the title compound (11 mg, 32%).

[0892] .sup.1H-NMR (400 MHz, DMSO-d.sub.6) : 8.32 (1H, d, J=8.2 Hz), 8.15 (1H, d, J=8.7 Hz), 8.01 (1H, s), 7.61 (1H, d, J=8.2 Hz), 7.35 (1H, d, J=1.8 Hz), 7.09 (1H, dd, J=8.7, 1.8 Hz), 4.19 (2H, t, J=5.9 Hz), 2.83 (2H, t, J=5.9 Hz), 2.58 (4H, q, J=7.0 Hz), 1.78 (6H, s), 1.00 (6H, t, J=7.0 Hz)

[0893] LCMS: m/z 402 [M+H].sup.+

[0894] HPLC retention time: 2.52 min (analysis condition W)

Example 36

Compound A7-18

N-[2-(3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yloxy)-ethyl]-acetamide

[0895] ##STR00051##

[0896] Under the same conditions as the method for synthesizing Compound A7-17, the title compound was prepared from Compound A6 and 2-chloroethylacetamide.

[0897] LCMS: m/z 388 [M+H].sup.+

[0898] HPLC retention time: 2.91 min (analysis condition W)

Example 37

Compound A7-19

[2-(3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yloxy)-ethyl]-carbamic Acid Ethyl Ester

[0899] ##STR00052##

[0900] Under the same conditions as the method for synthesizing Compound A7-17, the title compound was prepared from Compound A6 and ethyl-2-chloroethylcarbamate.

[0901] LCMS: m/z 418 [M+H].sup.+

[0902] HPLC retention time: 3.35 min (analysis condition W)

Example 38

Compound A7-20

[2-(3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yloxy)-ethyl]-urea

[0903] ##STR00053##

[0904] Under the same conditions as the method for synthesizing Compound A7-17, the title compound was prepared from Compound A6 and 2-chloroethylurea.

[0905] LCMS: m/z 399 [M+H].sup.+

[0906] HPLC retention time: 2.80 min (analysis condition W)

Example 39

Compound A7-21

6,6-Dimethyl-8-(oxetan-3-yloxy)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[0907] ##STR00054##

[0908] Under the same conditions as the method for synthesizing Compound A7-17, the title compound was prepared from Compound A6 and toluene-4-sulfonic acid oxetan-3-yl ester.

[0909] LCMS: m/z 359 [M+H].sup.+

[0910] HPLC retention time: 2.00 min (analysis condition S)

Example 40

Compound A7-22

6,6-Dimethyl-11-oxo-8-(pyrimidin-2-yloxy)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[0911] ##STR00055##

[0912] Under the same conditions as the method for synthesizing Compound A7-17, the title compound was prepared from Compound A6 and 2-bromopyrimidine.

[0913] LCMS: m/z 381 [M+H].sup.+

[0914] HPLC retention time: 2.00 min (analysis condition S)

Example 41

Compound A7-23

(3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yloxy)-ethyl Acetate Ester

[0915] ##STR00056##

[0916] Under the same conditions as the method for synthesizing Compound A7-17, the title compound was prepared from Compound A6 and 3-chloro-propionic acid ethyl ester.

[0917] LCMS: m/z 389 [M+H].sup.+

[0918] HPLC retention time: 3.37 min (analysis condition U)

Example 42

Compound A7-24

8-(2-Bromo-ethoxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[0919] ##STR00057##

[0920] Under the same conditions as the method for synthesizing Compound A7-1, the title compound was prepared from Compound A6 and 2-bromoethanol.

[0921] .sup.1H-NMR (270 MHz, DMSO-d.sub.6) : 12.75 (1H, br. s), 8.32 (1H, d, J=8.2 Hz), 8.17 (1H, d, J=8.6 Hz), 8.01 (1H, s), 7.61 (1H, dd, J=8.2, 1.4 Hz), 7.40 (1H, d, J=2.2 Hz), 7.12 (1H, dd, J=8.6, 2.2 Hz), 4.50 (2H, t, J=5.3 Hz), 3.88 (2H, t, J=5.3 Hz), 1.77 (6H, s).

[0922] LCMS: m/z 409, 411 [M+H].sup.+

[0923] HPLC retention time: 2.48 min (analysis condition S)

Example 43

Compound A7-25

6,6-Dimethyl-11-oxo-8-(piperidin-4-ylmethoxy)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile Hydrochloric Acid Salt

[0924] ##STR00058##

[0925] Under nitrogen atmosphere, 3-cyano-8-hydroxy-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one (Compound A6, 85 mg, 0.28 mmol) and triphenylphosphine (150 mg, 2 eq.) were added with THF (2 ml), and then further added dropwise with 4-hydroxymethyl-piperidine-1-carboxylic acid tert-butyl ester (120 mg, 2 eq.) and 2.19 N toluene solution of diethyl azodicarboxylic acid (0.26 mL, 2 eq.). The resultant was stirred at room temperature for 12 hr under nitrogen atmosphere. The residues obtained after concentrating the reaction solution under reduced pressure were purified by silica gel column chromatography (ethyl acetate/dichloromethane) to obtain 4-(3-cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yloxymethyl)-piperidine-1-carboxylic acid tert-butyl ester (white powder, 120 mg).

[0926] To the resulting compound, 4 N hydrochloric acid and dioxane solution was added under cooling. After stirring at room temperature for 2 hr, the solvent was removed under nitrogen stream. Then, the residues were washed with diethyl ether and then subjected to azeotropic treatment with toluene, followed by drying under vacuum and filtration to obtain the title compound (79 mg).

[0927] LCMS: m/z 399 [M+H].sup.+

[0928] HPLC retention time: 2.22 min (analysis condition C)

Example 44

Compound A8-1

6,6-Dimethyl-11-oxo-8-(piperidin-4-yloxy)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[0929] ##STR00059##

[0930] THF (0.5 mL) and TFA (0.5 mL) were added to 4-(3-cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yloxy)-piperidine-1-carboxylic acid tert-butyl ester (Compound A7-1, 35 mg, 0.072 mmol), and the mixture was stirred at room temperature until Compound A7-1 disappears. The reaction solution was concentrated under reduced pressure and the residue was desalinated by using anion exchanger PL StratoSpheres (trademark) PL-HCO3 MP to obtain the title compound (37 mg, 76%).

[0931] .sup.1H-NMR (400 MHz, CD.sub.3OD) : 8.38 (1H, d, J=7.9 Hz), 8.24 (1H, d, J=8.5 Hz), 7.85 (1H, s), 7.53 (1H, d, J=7.9 Hz), 7.27 (1H, s), 7.09 (1H, d, J=8.5 Hz), 4. 67-4.76 (1H, m), 3.07-3.20 (2H, m), 2.77-2.87 (2H, m), 2.03-2.15 (2H, m), 1.80 (6H, s), 1.69-1.77 (2H, m)

[0932] LCMS: m/z 386 [M+H].sup.+

[0933] HPLC retention time: 2.51 min (analysis condition W)

Example 45

Compound A8-2

8-(2-Amino-ethoxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[0934] ##STR00060##

[0935] Under the same conditions as the method for synthesizing Compound A8-1, the title compound was prepared from Compound A7-3.

[0936] LCMS: m/z 346 [M+H].sup.+

[0937] HPLC retention time: 2.40 min (analysis condition W)

Example 46

Compound A8-3

8-(2-Methanesulfonyl-ethoxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[0938] ##STR00061##

[0939] Under the same conditions as the method for synthesizing Compound B3-8, the title compound was prepared from Compound A7-5.

[0940] LCMS: m/z 409 [M+H].sup.+

[0941] HPLC retention time: 3.13 min (analysis condition W)

Example 47

Compound A8-4

8-(2-Methanesulfinyl-ethoxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[0942] ##STR00062##

[0943] The title compound was obtained as a by-product of the synthesis of Compound A8-3.

[0944] LCMS: m/z 393 [M+H].sup.+

[0945] HPLC retention time: 2.87 min (analysis condition W)

Example 48

Compound A8-5

5,6,6-Trimethyl-11-oxo-8-(tetrahydro-pyran-4-yloxy)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[0946] ##STR00063##

[0947] Under the same conditions as the method for synthesizing Compound A10-1, the title compound was prepared from Compound A7-6.

[0948] LCMS: m/z 401 [M+H].sup.+

[0949] HPLC retention time: 2.72 min (analysis condition S)

Example 49

Compound A8-6-1

2-Bromo-8-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[0950] ##STR00064##

[0951] 8-Methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (Compound A5-2, 50 mg, 0.158 mmol) was dissolved in CH.sub.3CN (1 mL), added with NBS (56 mg, 2 eq.), and stirred at 80 C. overnight. The reaction solution was added to water, and then extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over sodium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were added with MeOH and the solid remained after dissolution was filtered to obtain the target compound (yellow powder, 20 mg, 38%).

[0952] .sup.1H-NMR (400 MHz, DMSO-d.sub.6) : 12.92 (1H, s), 8.50 (1H, s), 8.16 (1H, d, J=8.5 Hz), 8.14 (1H, s), 7.36 (1H, d, J=2.4 Hz), 7.11 (1H, dd, J=8.5, 2.4 Hz), 3.92 (3H, s), 1.78 (6H, s).

[0953] LCMS: m/z 395, 397 [M+H].sup.+

[0954] HPLC retention time: 2.57 min (analysis condition S)

Example 50

Compound A8-6-2

2-Bromo-8-hydroxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[0955] ##STR00065##

[0956] Under the same conditions as the method for synthesizing Compound A6, the title compound was prepared from Compound A8-6-1.

[0957] .sup.1H-NMR (400 MHz, DMSO-d.sub.6) : 8.46 (1H, s), 8.10 (1H, s), 8.05 (1H, d, J=8.6 Hz), 7.13 (1H, d, J=2.1 Hz), 6.89 (1H, dd, J=8.5, 2.1 Hz), 1.71 (6H, s).

[0958] LCMS: m/z 381,383 [M+H].sup.+

[0959] HPLC retention time: 2.10 min (analysis condition S)

Example 51

Compound A8-6-3

2-Bromo-8-(2-diethylamino-ethoxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[0960] ##STR00066##

[0961] Under the same conditions as the method for synthesizing Compound A7-17, the title compound was prepared from Compound A8-6-2.

[0962] .sup.1H-NMR (400 MHz, CD.sub.3OD) : 8.53 (1H, d, J=0.5 Hz), 8.20 (1H, d, J=8.7 Hz), 7.88 (1H, d, J=0.5 Hz), 7.28 (1H, d, J=2.3 Hz), 7.05 (1H, dd, J=8.9, 2.5 Hz), 4.24 (2H, t, J=5.7 Hz), 2.96 (2H, t, J=5.7 Hz), 2.70 (4H, q, J=7.1 Hz), 1.79 (6H, s), 1.12 (6H, t, J=7.2 Hz).

[0963] LCMS: m/z 480, 482 [M+H].sup.+

[0964] HPLC retention time: 1.73 min (analysis condition S)

Example 52

Compound A8-7

(3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yloxy)-acetic Acid

[0965] ##STR00067##

[0966] (3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yloxy)-ethyl acetate ester (Compound A7-23, 180 mg, 0.464 mmol) and potassium hydroxide (130 mg, 2.32 mmol) were dissolved in THF (10 ml) and water (1.8 mL), and stirred at 70 C. for 2 hr. After cooling to room temperature, the mixture was extracted with dichloromethane. Water layer () was adjusted to be acidic by using 1 N hydrochloric acid, and the precipitated solid was filtered and washed several times with water to obtain the title compound (white solid, 130 mg, 78%).

[0967] .sup.1H-NMR (300 MHz, DMSO) ppm 13.09 (s, 1H), 8.31 (d, 1H, J=8.1 Hz), 8.11 (d, 1H, J=8.4 Hz), 8.01 (s, 1H), 7.58 (d, 1H, J=7.8 Hz), 7.25 (d, 1H, J=2.1 Hz), 6.97 (d, 1H, J=8.4 Hz), 4.51 (s, 2H), 1.73 (s, 6H)

[0968] LCMS: m/z 361 [M+H].sup.+

[0969] HPLC retention time: 2.97 min (analysis condition U)

Example 53

Compound A8-8

6,6-Dimethyl-8-(2-morpholin-4-yl-ethoxy)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[0970] ##STR00068##

[0971] Under the same conditions as the method for synthesizing Compound A8-17, the title compound was prepared from Compound A7-24 and morpholine.

[0972] .sup.1H-NMR (500 MHz, CD.sub.3OD+CDCl.sub.3) ppm; 8.4 (d, 1H, J=8.2 Hz), 8.3 (d, 1H, J=8.7 Hz), 7.8 (s, 1H), 7.5 (dd, 1H, J=1.1 Hz, J=8.2 Hz), 7.2 (d, 1H, J=2.3 Hz), 7.0 (dd, 1H, J=2.2 Hz, J=8.7 Hz), 4.2 (t, 2H, J=5.3 Hz), 3.7 (t, 4H, J=4.5 Hz), 2.9 (t, 2H, J=5.3 Hz), 2.6 (t, 4H, J=4.5 Hz), 1.8 (s, 6H)

[0973] LCMS: m/z 416 [M+H].sup.+

[0974] HPLC retention time: 2.40 min (analysis condition U)

Example 54

Compound A8-9

8-[2-(1,1-Dioxothiomorpholino)-ethoxy]-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[0975] ##STR00069##

[0976] Under the same conditions as the method for synthesizing Compound A7-17, the title compound was prepared from Compound A7-24 and thiomorpholine-1,1-dioxide.

[0977] .sup.1H-NMR (400 MHz, DMSO-d.sub.6) : 12.72 (1H, s), 8.31 (1H, d, 8.5 Hz), 8.15 (1H, d, 8.5 Hz), 8.00 (1H, s), 7.60 (1H, d, 8.5 Hz), 7.36 (1H, d, 1.8 Hz), 7.10 (1H, dd, 1.8, 8.5), 4.25 (2H, t, 5.5 Hz), 3.06-3.33 (8H, m), 2.97 (2H, t, 5.5), 1.77 (6H, s)

[0978] LCMS: m/z 464 [M+H].sup.+

[0979] HPLC retention time: 2.70 min (analysis condition W)

Example 55

Compound A8-10

8-(2-Tert-butylamino-ethoxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[0980] ##STR00070##

[0981] Under the same conditions as the method for synthesizing Compound A7-17, the title compound was prepared from Compound A7-24 and tert-butylamine.

[0982] .sup.1H-NMR (400 MHz, DMSO-d.sub.6) : 12.71 (1H, s), 8.32 (1H, d, 7.9 Hz), 8.15 (1H, d, 9.1 Hz), 8.07 (1 d, 1.8 Hz), 7.60 (1H, dd, 1.8, 7.9 Hz), 7.35 (1H, d, 2.4 Hz), 7.09 (1H, dd, 2.4, 9.1 Hz), 4.16 (2H, t, 6.1 Hz), 2.91 (2H, t, 6.1 Hz), 1.77 (6H, s), 1.08 (9H, s)

[0983] LCMS: m/z 402 [M+H].sup.+

[0984] HPLC retention time: 2.55 min (analysis condition W)

Example 56

Compound A8-11

8-(2-Sec-butylamino-ethoxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[0985] ##STR00071##

[0986] Under the same conditions as the method for synthesizing Compound A8-17, the title compound was prepared from Compound A7-24 and sec-butylamine.

[0987] LCMS: m/z 402 [M+H].sup.+

[0988] HPLC retention time: 1.88 min (analysis condition U)

Example 57

Compound A8-12

8-[2-(2-Hydroxy-1,1-dimethyl-ethylamino)-ethoxy]-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[0989] ##STR00072##

[0990] Under the same conditions as the method for synthesizing Compound A8-17, the title compound was prepared from Compound A7-24 and 2-amino-2-methyl-propan-1-ol.

[0991] .sup.1H-NMR (300 MHz, DMSO-d.sub.6) ppm; 12.65 (brs, 1H), 8.31 (d, 1H, J=8.0 Hz), 8.15 (d, 1H, J=8.8 Hz), 7.99 (s, 1H), 7.59 (d, 1H, J=8.0 Hz), 7.34 (d, 1H, J=2.3 Hz), 7.08 (dd, 1H, J=2.2 Hz, J=8.8 Hz), 4.58 (brs, 1H), 4.16 (t, 2H, J=5.7 Hz), 3.20 (s, 2H), 2.88 (t, 2H, J=5.7 Hz), 1.76 (s, 6H), 0.97 (s, 6H)

[0992] LCMS: m/z 418 [M+H].sup.+

[0993] HPLC retention time: 2.47 min (analysis condition U)

Example 58

Compound A8-13

8-[2-(4-Ethyl-piperazin-1-yl)-ethoxy]-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[0994] ##STR00073##

[0995] Under the same conditions as the method for synthesizing Compound A8-17, the title compound was prepared from Compound A7-24 and 1-ethyl-piperazine.

[0996] LCMS: m/z 443 [M+H].sup.+

[0997] HPLC retention time: 1.68 min (analysis condition U)

Example 59

Compound A8-14

8-(2-Imidazol-1-yl-ethoxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[0998] ##STR00074##

[0999] Under the same conditions as the method for synthesizing Compound A7-1, the title compound was prepared from Compound A6 and 2-imidazol-1-yl-ethanol.

[1000] .sup.1H-NMR (300 MHz, DMSO-d.sub.6) ppm; 12.71 (s, 1H), 8.31 (d, 1H, J=8.3 Hz), 8.14 (d, 1H, J=8.8 Hz), 7.99 (s, 1H), 7.73 (s, 1H), 7.60 (d, 1H, J=8.3 Hz), 7.34 (s, 1H), 7.29 (s, 1H), 7.09 (d, 1H, J=8.8 Hz), 6.91 (s, 1H), 4.20 (s, 4H), 1.76 (s, 6H)

[1001] LCMS: m/z 387 [M+H].sup.+

[1002] HPLC retention time: 1.77 min (analysis condition U)

Example 60

Compound A8-15

8-{2-[Bis-(2-hydroxy-ethyl)-amino]-ethoxy}-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1003] ##STR00075##

[1004] According to the same method as the method for synthesizing Compound A7-17, the title compound was prepared from Compound A7-24 and 2-(2-hydroxy-ethylamino)-ethanol.

[1005] LCMS: m/z 434 [M+H].sup.+

[1006] HPLC retention time: 2.40 min (analysis condition U)

Example 61

Compound A8-16

1-[2-(3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yloxy)-ethyl]-piperidine-4-carboxylic Acid Amide

[1007] ##STR00076##

[1008] Under the same conditions as the method for synthesizing Compound A8-17, the title compound was prepared from Compound A7-24 and piperidine-4-carboxylic acid amide.

[1009] LCMS: m/z 457 [M+H].sup.+

[1010] HPLC retention time: 1.28 min (analysis condition S)

Example 62

Compound A8-17

6,6-Dimethyl-11-oxo-8-[2-(3-oxo-piperazin-1-yl)-ethoxy]-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1011] ##STR00077##

[1012] To DMF solution (5 mL) of 8-(2-bromo-ethoxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (Compound A7-24, 30 mg, 0.07 mmol), piperazin-2-one (44.9 mg, 0.35 mmol) and N,N-diisopropylethylamine (0.061 mL, 0.35 mmol) were added at room temperature and stirred at 80 C. for 18 hr. After cooling to room temperature, the mixture was extracted with ethyl acetate washed with saturated brine. The organic layer was dried over magnesium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were purified by preparative TLC (dichloromethane/methanol) to obtain the title compound (white solid, 24 mg, 80%).

[1013] .sup.1H-NMR (300 MHz, DMSO-d.sub.6) ppm; 12.71 (s, 1H), 8.32 (d, 1H, J=8.4 Hz), 8.15 (d, 1H, J=8.8 Hz), 8.00 (s, 1H), 7.75 (s, 1H), 7.60 (d, 1H, J=8.4 Hz), 7.37 (d, 1H, J=2.3 Hz), 7.09 (dd, 1H, J=2.3 Hz, J=8.8 Hz), 4.27 (t, 2H, J=5.7 Hz), 3.19 (m, 2H), 3.08 (s, 2H), 2.83 (t, 2H, J=5.7 Hz), 2.70 (t, 2H, J=5.7 Hz), 1.8 (s, 6H)

[1014] LCMS: m/z 429 [M+H].sup.+

[1015] HPLC retention time: 1.29 min (analysis condition S)

Example 63

Compound A8-18

Morpholine-4-sulfonic acid[2-(3-cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yloxy)-ethyl]-amide

[1016] ##STR00078##

[1017] The title compound was obtained as a by-product of the synthesis of Compound C.sub.1-2.

[1018] LCMS: m/z 495 [M+H].sup.+

[1019] HPLC retention time: 2.00 min (analysis condition S)

Example 64

Compound A8-19

4-Methyl-piperazine-1-sulfonic acid [2-(3-cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yloxy)-ethyl]-amide

[1020] ##STR00079##

[1021] The title compound was obtained as a by-product of the synthesis of Compound C1-4.

[1022] .sup.1H-NMR (300 MHz, DMSO-d.sub.6) : 1.77 (6H, s), 2.16 (3H, s), 2.34 (4H, m), 3.08 (4H, m), 3.35 (2H, m), 4.19 (2H, t, 5.34 Hz), 7.09 (1H, dd, 8.77 Hz, 2.99 Hz), 7.37 (1H, bs, 1.91 Hz), 7.59 (2H, m), 8.01 (1H, s), 8.16 (1H, d, 8.40 Hz), 8.32 (1H, d, 8.01 Hz), 12.7 (1H, s).

[1023] LCMS: m/z 501 [M+H].sup.+

[1024] HPLC retention time: 1.43 min (analysis condition S)

Example 65

Compound A8-20

6,6-Dimethyl-8-(1-oxetan-3-yl-piperidin-4-ylmethoxy)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1025] ##STR00080##

[1026] 6,6-Dimethyl-11-oxo-8-(piperidin-4-ylmethoxy)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile hydrochloric acid salt (Compound A7-25, 30 mg, 0.075 mmol) and oxetan-3-one (38 mg, 7 eq.) were dissolved in acetic acid (0.2 ml), THF (1 ml) and methanol (1 ml), added with sodium cyanoborohydride (33 mg, 7 eq.) at room temperature, and stirred overnight. The reaction solution was added with water, and then extracted with ethyl acetate. The solution was dried over sodium sulfate and the solvent was removed under vacuum and the resulting residues were purified by preparative TLC (chloroform: 2 N ammonia methanol=9:1) to obtain the target compound (15 mg).

[1027] LCMS: m/z 456 [M+H].sup.+

[1028] HPLC retention time: 2.78 min (analysis condition C)

Example 66

Compound A8-21

6,6-Dimethyl-8-[2-(1-oxetan-3-yl-piperidin-4-yl)-ethoxy]-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1029] ##STR00081##

[1030] Under the same conditions as the method for synthesizing Compound A7-25, and Compound A8-20, the title compound was prepared from Compound A6 and 4-(2-hydroxy-ethyl)-piperidine-1-carboxylic acid tert-butyl ester (15 mg).

[1031] LCMS: m/z 470 [M+H].sup.+

[1032] HPLC retention time: 2.85 min (analysis condition C)

Example 67

Compound A9-1

N-[2-(3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yloxy)-ethyl]-methanesulfonamide

[1033] ##STR00082##

[1034] Trifluoroacetic acid salt of 8-(2-amino-ethoxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (Compound A8-2, 19 mg, 0.044 mmol) was suspended in dichloromethane (0.5 mL), added with diisopropylethylamine (0.0157 mL, 2 eq.) and methanesulfonyl chloride (0.0034 mL, 1 eq.), and then stirred at room temperature for 2 hr. The reaction solution was added to water, and then extracted with dichloromethane. After washing with saturated brine, the organic layer was dried over sodium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were separated by silica gel preparative TLC (ethyl acetate 100%) to obtain the target compound (5.5 mg, 29%).

[1035] .sup.1H-NMR (400 MHz, DMSO-d.sub.6) : 8.47 (1H, d, J=8.2 Hz), 8.32 (1H, d, J=8.7 Hz), 8.16 (1H, s), 7.76 (1H, d, J=8.2 Hz), 7.53-7.46 (2H, m), 7.26 (1H, d, J=8.7 Hz), 4.39-4.33 (2H, m), 3.58-3.51 (2H, m), 3.12 (3H, s), 1.93 (6H, s)

[1036] LCMS: m/z 424 [M+H].sup.+

[1037] HPLC retention time: 3.10 min (analysis condition W)

Example 68

Compound A9-2

N-[2-(3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yloxy)-ethyl]-2,2,2-trifluoro-acetamide

[1038] ##STR00083##

[1039] The title compound was obtained as a by-product of the synthesis of Compound A9-1.

[1040] LCMS: m/z 442 [M+H].sup.+

[1041] HPLC retention time: 3.45 min (analysis condition W)

Example 69

Compound A9-3-1

8-{2-(Tert-butyloxycarbonylaminosulfonyl)amino-ethoxy}-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1042] ##STR00084##

[1043] Trifluoroacetic acid salt of 8-(2-amino-ethoxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (Compound A8-2, 20 mg, 0.044 mmol) was dissolved in pyridine (0.5 mL), added with N-(tert-butoxycarbonyl)-N-[4-(dimethyl azaniumylidene)-1,4-dihydropyridin-1-yl sulfonyl]azanide (13.5 mg, 1 eq.), and then stirred at room temperature for 14 hr. The reaction solution was added to water, and then extracted with ethyl acetate. After washing with saturated brine, the organic layer was dried over sodium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were separated by silica gel preparative TLC(ethyl acetate) to obtain the title compound (16.1 mg, 68%).

[1044] .sup.1H-NMR (400 MHz, DMSO-d.sub.6) : 12.74 (1H, s), 10.94 (1H, s), 8.33 (1H, d, J=8.5 Hz), 8.16 (1H, d, J=9.1 Hz), 8.02 (1H, s), 7.84 (1H, br. s), 7.62 (1H, d, J=7.9 Hz), 7.36 (1H, s), 7.10 (1H, d, J=7.9 Hz). 4.24-4.18 (2H, m), 1.78 (6H, s), 1.32 (9H, s)

[1045] LCMS: m/z 525 [M+H].sup.+

[1046] HPLC retention time: 3.48 min (analysis condition W)

Example 70

Compound A9-3-2

8-{2-(Methylaminosulfonyl)amino-ethoxy}-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1047] ##STR00085##

[1048] Under the same conditions as the method for synthesizing Compound A8-1, the title compound was prepared from Compound A9-3-1.

[1049] LCMS: m/z 425 [M+H].sup.+

[1050] HPLC retention time: 2.95 min (analysis condition W)

Example 71

Compound A9-4

8-(1-Methanesulfonyl-piperidin-4-yloxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1051] ##STR00086##

[1052] According to the same method as the method for synthesizing Compound A7-17, the title compound was prepared from Compound A8-1 and methanesulfonyl chloride.

[1053] .sup.1H-NMR (400 MHz, DMSO-d.sub.6) : 12.72 (1H, s), 8.30 (1H, d, J=8.5 Hz), 8.14 (1H, d, J=8.5 Hz), 8.00 (1H, s), 7.59 (1H, d, J=7.9 Hz), 7.38 (1H, s), 7.13 (1H, d, J=8.5 Hz), 4.81 (1H, s), 3.39-3.38 (2H, m), 3.19-3.13 (2H, m), 2.93 (3H, s), 2.11-2.04 (2H, m), 1.83-1.75 (8H, m).

[1054] LCMS: m/z 464 [M+H].sup.+

[1055] HPLC retention time: 3.41 min (analysis condition U)

Example 72

Compound A9-5

8-[1-(2-Methoxy-ethyl)-piperidin-4-yloxy]-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1056] ##STR00087##

[1057] Under the same conditions as the method for synthesizing Compound A9-1, the title compound was prepared from Compound A8-1 and 1-bromo-2-methoxy-ethane.

[1058] .sup.1H-NMR (400 MHz, CDCl.sub.3) : 8.48-8.53 (1H, m), 8.32-8.38 (1H, m), 7.74-7.77 (1H, m), 7.50-7.55 (1H, m), 7.07-7.10 (1H, m), 6.95-7.00 (1H, m), 4.43-4.51 (1H, m), 3.53 (2H, t, J=5.6 Hz), 3.36 (3H, s), 2.77-2.87 (2H, m), 2.62 (2H, t, J=5.6 Hz), 2.35-2.47 (2H, m), 2.02-2.12 (2H, m), 1.78-1.95 (2H, m), 1.82 (6H, s).

[1059] LCMS: m/z 444 [M+H].sup.+

[1060] HPLC retention time: 2.00 min (analysis condition U)

Example 73

Compound A9-6-2

8-[1-(2-Hydroxy-ethyl)-piperidin-4-yloxy]-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1061] ##STR00088##

[1062] According to the same method as the method for synthesizing Compound A7-17, the title compound was prepared from Compound A8-1 and (2-bromoethoxy)-tert-butyldimethylsilane, followed by treatment with tetrabutylammonium fluoride.

[1063] LCMS: m/z 430 [M+H].sup.+

[1064] HPLC retention time: 1.45 min (analysis condition S)

Example 74

Compound A9-7

8-[1-(2-Fluoro-ethyl)-piperidin-4-yloxy]-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1065] ##STR00089##

[1066] According to the same method as the method for synthesizing Compound A7-17, the title compound was prepared from Compound A8-1 and methanesulfonic acid 2-fluoroethyl ester.

[1067] .sup.1H-NMR (300 MHz, DMSO-d.sub.6) : 1.67 (2H, m), 1.76 (6H, s), 2.01 (2H, m), 2.37 (2H, t, 11.0 Hz), 2.61 (1H, t, 4.20 Hz), 2.70 (1H, t, 4.58), 2.78 (2H, m), 4.46 (1H, t, 4.58 Hz), 4.62 (2H, t, 5.34 Hz), 7.10 (1H, dd, 9.16 Hz, 2.29 Hz), 7.34 (1H, bs, 1.53 Hz), 7.60 (1H, dd, 8.40 Hz, 1.53 Hz), 7.99 (1H, s), 8.13 (1H, d, 8.39 Hz), 8.30 (1H, d, 8.39 Hz), 12.7 (1H, s).

[1068] LCMS: m/z 432 [M+H].sup.+

[1069] HPLC retention time: 1.52 min (analysis condition S)

Example 75

Compound A9-8

8-(1-Acetyl-piperidin-4-yloxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1070] ##STR00090##

[1071] According to the same method as the method for synthesizing Compound A7-17, the title compound was prepared from Compound A8-1 and acetyl chloride.

[1072] LCMS: m/z 428 [M+H].sup.+

[1073] HPLC retention time: 1.91 min (analysis condition S)

Example 76

Compound A9-9

2-(3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yloxy)-acetamide

[1074] ##STR00091##

[1075] Under the same conditions as the method for synthesizing Compound A7-17, the title compound was prepared from Compound A6 and 2-bromo-acetamide.

[1076] LCMS: m/z 360 [M+H].sup.+

[1077] HPLC retention time: 2.83 min (analysis condition U)

Example 77

Compound A9-10

2-(3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yloxy)-N-methyl-acetamide

[1078] ##STR00092##

[1079] (3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yloxy)-acetic acid (Compound A8-7, 30 mg, 0.0838 mmol), methylamine hydrochloric acid salt (28.1 mg, 0.417 mmol), EDC (32 mg, 0.167 mmol) and HOBT (0.023 mg, 0.167 mmol) were dissolved in DMF (1 mL), and added with diisopropylethylamine (0.145 mL, 0.833 mmol) at room temperature. After stirring at room temperature for 18 hr, water was added and the extraction was carried out with ethyl acetate. After washing with saturated brine, the organic layer was dried over magnesium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were dissolved in dichloromethane, added with diethyl ether, and the precipitated title compound was obtained (white solid, 19.7 mg, 63%).

[1080] .sup.1H-NMR (300 MHz, DMSO) ppm 12.73 (s, 1H), 8.33 (d, 1H, J=8.1 Hz), 8.17 (d, 1H, J=8.7 Hz), 8.13 (s, 1H), 8.00 (s, 1H), 7.62 (d, 1H, J=8.1 Hz), 7.39 (d, 1H, J=2.4 Hz), 7.11 (dd, 1H, J=8.7 Hz, 2.4 Hz), 4.64 (s, 2H), 3.17 (d, 1H, J=5.4 Hz), 2.69 (d, 1H, J=4.5 Hz), 1.76 (s, 6H)

[1081] LCMS: m/z 374 [M+H].sup.+

[1082] HPLC retention time: 2.43 min (analysis condition U)

Example 78

Compound A9-11

2-(3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yloxy)-N-(2,2-dimethyl-[1,3]dioxolan-4-ylmethyl)-acetamide

[1083] ##STR00093##

[1084] Under the same conditions as the method for synthesizing Compound A9-10, the title compound was prepared from Compound A8-7 and C-(2,2-dimethyl-[1,3]dioxolan-4-yl)-methylamine.

[1085] LCMS: m/z 474 [M+H].sup.+

[1086] HPLC retention time: 2.20 min (analysis condition U)

Example 79

Compound A9-12

2-(3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yloxy)-N-(2,3-dihydroxy-propyl)-acetamide

[1087] ##STR00094##

[1088] Under the same conditions as the method for synthesizing Compound A7-14-2, the title compound was prepared from Compound A9-11.

[1089] LCMS: m/z 434 [M+H].sup.+

[1090] HPLC retention time: 1.72 min (analysis condition U)

Example 80

Compound A9-13

2-Methyl-acrylic acid 2-[2-(3-cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yloxy)-acetylamino]-ethyl ester

[1091] ##STR00095##

[1092] Under the same conditions as the method for synthesizing Compound A9-10, the title compound was prepared from Compound A8-7 and 2-methyl-acrylic acid 2-amino-ethyl ester.

[1093] LCMS: m/z 472 [M+H].sup.+

[1094] HPLC retention time: 3.30 min (analysis condition U)

Example 81

Compound A9-14

2-(3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yloxy)-N-(2-hydroxy-ethyl)-acetamide

[1095] ##STR00096##

[1096] 2-Methyl-acrylic acid 2-[2-(3-cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yloxy)-acetylamino]-ethyl ester (Compound A9-13, 40 mg, 0.085 mmol) was dissolved in a mixture solvent of methanol (2 mL) and water (2 mL), added with potassium hydroxide (48 mg, 0.85 mmol), and then stirred at room temperature for 18 hr. After the neutralization with 1 N hydrochloric acid, the reaction solution was concentrated under reduced pressure. The resulting residues were purified by amino silica gel to obtain the title compound (white solid, 8.9 mg, 26%).

[1097] .sup.1H-NMR (300 MHz, DMSO) ppm 12.75 (s, 1H), 8.32 (d, 1H, J=8.1 Hz), 8.17-8.13 (m, 2 Hz), 7.99 (s, 1H), 7.60 (d, 1H, J=8.1 Hz), 7.38 (d, 1H, J=1.8 Hz), 7.11 (dd, 1H, J=2.1 Hz, 8.7 Hz), 4.72 (t, 1H, J=5.7 Hz), 4.65 (s, 1H), 3.48 (dd, 2H, J=12.0 Hz, 6.0 Hz), 3.26 (dd, 2H, J=12.0 Hz, 6.0 Hz), 1.76 (s, 6H)

[1098] LCMS: m/z 404 [M+H].sup.+

[1099] HPLC retention time: 2.83 min (analysis condition U)

Example 82

Compound A9-15-1

4-[2-(3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yloxy)-acetyl]-piperazine-1-carboxylic Acid Tert-Butyl Ester

[1100] ##STR00097##

[1101] (3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yloxy)-acetic acid (Compound A8-7, 30 mg, 0.083 mmol), piperazine-1-carboxylic acid tert-butyl ester (31 mg, 2 eq.), and HOBt (30 mg, 3 eq.) were dissolved in 0.5 ml DMF, added with EDC (48 mg, 3 eq.), and stirred at room temperature overnight. Thereafter, the solvent was removed under reduced pressure and the resulting residues were purified by preparative TLC to obtain the title compound (20 mg).

[1102] LCMS: m/z 527, 471, 427[MH].sup.

[1103] HPLC retention time: 2.77 min (analysis condition C)

Example 83

Compound A9-15-2

6,6-Dimethyl-11-oxo-8-(2-oxo-2-piperazin-1-yl-ethoxy)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile Hydrochloric Acid Salt

[1104] ##STR00098##

[1105] 4-[2-(3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yloxy)-acetyl]-piperazine-1-carboxylic acid tert-butyl ester (Compound A9-15-1, 20 mg) was added with 4 N hydrochloric acid and dioxane solution (1 ml), and stirred in an water bath at 10 C. for 4 hr. Water was added to the reaction solution and the resulting precipitates were filtered and dried to obtain the title compound (15 mg, white powder).

[1106] LCMS: m/z 429 [M+H].sup.+

[1107] HPLC retention time: 0.81 min (analysis condition I)

Example 84

Compound A9-16

2-(3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yloxy)-N-(2-cyano-ethyl)-acetamide

[1108] ##STR00099##

[1109] (3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yloxy)-acetic acid (Compound A8-7, 30 mg, 0.083 mmol), 3-aminopropionitrile (12 mg, 2 eq.) and HOBt (30 mg, 3 eq.) were dissolved in 0.5 ml DMF, added with EDC (48 mg, 3 eq.), and stirred at room temperature overnight. Thereafter, the solvent was removed under reduced pressure and the resulting residues were purified by preparative TLC to obtain the title compound (23 mg).

[1110] LCMS: m/z 411 [M+H].sup.+

[1111] HPLC retention time: 2.27 min (analysis condition C)

Example 85

Compound A9-17

2-(3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yloxy)-N-(2-cyano-ethyl)-N-methyl-acetamide

[1112] ##STR00100##

[1113] (3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yloxy)-acetic acid (Compound A8-7, 30 mg, 0.083 mmol), N-methyl-3-aminopropionitrile (14 mg, 2 eq.) and HOBt (30 mg, 3 eq.) were dissolved in 0.5 ml DMF, added with EDC (48 mg, 3 eq.), and stirred at room temperature overnight. Thereafter, the solvent was removed under reduced pressure and the resulting residues were purified by preparative TLC to obtain the title compound (7 mg).

[1114] LCMS: m/z 411 [M+H].sup.+

[1115] HPLC retention time: 2.33 min (analysis condition C)

Example 86

Compound A10

8-(Tert-butyl-dimethyl-silanyloxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1116] ##STR00101##

[1117] The DMF solution of 8-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (Compound A6, 100 mg, 0.331 mmol), imidazole (67.5 mg, 3 eq.) and tert-butylchlorodimethylsilane (92.4 mg, 1.5 eq.) was stirred overnight at room temperature. To the reaction solution, saturated aqueous solution of sodium hydrogen carbonate was added followed by extraction with tert-butylmethyl ether. The organic layer was washed with brine and dried over sodium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain the target compound (white solid, 170 mg, 100%).

[1118] LCMS: m/z 417 [M+H].sup.+

[1119] HPLC retention time: 3.38 min (analysis condition S)

Example 87

Compound A10-1

8-Methoxy-5,6,6-trimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1120] ##STR00102##

[1121] To the THF solution of triphenylphosphine (260 mg, 3 eq.), azodicarboxylic acid diisopropyl ester (0.195 ml, 3 eq.) was added and the mixture was stirred at room temperature for 1 hr. Thereafter, 8-(tert-butyldimethylsilanyloxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (Compound A10, 138 mg, 0.331 mmol) and methanol (1 ml) were added and stirred overnight. The reaction solution was purified by HPLC to obtain the target compound (44.8 mg, 41%).

[1122] .sup.1H-NMR (270 MHz, DMSO-d.sub.6) : 8.44 (1H, d, J=8.1 Hz), 8.33 (1H, s), 8.14 (1H, d, J=8.7 Hz), 7.66 (1H, dd, J=8.2, 1.1 Hz), 7.39 (1H, d, J=2.3 Hz), 7.09 (1H, dd, J=8.7, 2.3 Hz), 4.17 (3H, s), 3.92 (3H, s), 1.88 (6H, s).

[1123] LCMS: m/z 331 [M+H].sup.+

[1124] HPLC retention time: 2.35 min (analysis condition S)

Example 88

Compound A10-2

8-(1-Methanesulfonyl-piperidin-4-yloxy)-5,6,6-trimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1125] ##STR00103##

[1126] Under the same conditions as the method for synthesizing Compound B3-4, the title compound was prepared from Compound A9-4.

[1127] LCMS: m/z 478 [M+H].sup.+

[1128] HPLC retention time: 2.68 min (analysis condition U)

Example 89

Compound B1

Trifluoro-methanesulfonic Acid 3-cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl ester

[1129] ##STR00104##

[1130] 8-Hydroxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (Compound A6, 550 mg, 0.189 mmol) was dissolved in pyridine (18 mL), added with anhydrous trifluoromethanesulfonic acid (0.758 ml, 3 eq.), and stirred at room temperature for 30 min. The reaction solution was added to water and then extracted with dichloromethane. The organic layer was dried over magnesium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain the target compound (white powder, 641 mg, 81%).

[1131] .sup.1H-NMR (400 MHz, DMSO-d.sub.6) : 12.89 (1H, br. s), 8.36 (1H, d, J=8.8 Hz), 8.31 (1H, dd, J=8.1, 0.7 Hz), 8.11 (1H, d, J=2.3 Hz), 8.04 (1H, dd, J=1.5, 0.7 Hz), 7.65-7.60 (2H, m). 1.76 (6H, s)

[1132] LCMS: m/z 435 [M+H].sup.+

[1133] HPLC retention time: 3.10 min (analysis condition U)

Example 90

Compound B2-1

8-(4-Isopropyl-piperazin-1-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1134] ##STR00105##

[1135] Trifluoro-methanesulfonic acid 3-cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl ester (Compound B1, 40 mg, 0.0921 mmol) was dissolved in NMP (1 ml) and added with 1-isopropylpiperazine (236 mg, 20 eq.). The mixture was stirred at 120 C. for 3 hr. After cooling to room temperature, purification was carried out by HPLC to obtain the target compound (white powder, 12.8 mg, 34%).

[1136] .sup.1H-NMR (270 MHz, DMSO-d.sub.6) : 8.30 (1H, d, 8.1 Hz), 8.03 (1H, d, 8.6 Hz), 7.98 (1H, s), 7.56 (1H, d, 8.6 Hz), 7.21 (1H, s), 7.04 (1H, d, 9.1 Hz), 3.40-3.37 (4H, m), 2.73-2.65 (1H, m), 2.61-2.58 (4H, m), 1.75 (6H, s), 1.02 (6H, d, 6.6 Hz)

[1137] LCMS: m/z 413 [M+H].sup.+

Example 91

Compound B2-2

8-[4-(2-Hydroxy-ethyl)-piperazin-1-yl]-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1138] ##STR00106##

[1139] According to the same method as the method for synthesizing Compound B2-1, the title compound was prepared from Compound B1 and N-(2-hydroxyethyl)piperazine.

[1140] .sup.1H-NMR (270 MHz, DMSO-d.sub.6) : 8.30 (1H, d, 8.1 Hz), 8.03 (1H, d, 8.7 Hz), 7.99 (1H, s), 7.58 (1H, d, 7.9 Hz), 7.21 (1H, s), 7.04 (1H, d, 8.7 Hz), 4.50-4.46 (1H, br m), 3.59-3.53 (2H, m), 3.39-3.35 (4H, m), 2.59-2.56 (4H, m), 2.45 (2H, t, 6.1 Hz), 1.76 (6H, s)

[1141] LCMS: m/z 415 [M+H].sup.+

[1142] HPLC retention time: 1.27 min (analysis condition S)

Example 92

Compound B2-3

6,6-Dimethyl-8-morpholin-4-yl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1143] ##STR00107##

[1144] Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound B1 and morpholine.

[1145] .sup.1H-NMR (400 MHz, DMSO-d.sub.6) : 12.62 (1H, br. s), 8.29 (1H, d, 8.2 Hz), 8.04 (1H, d, 9.0 Hz), 7.96 (1H, s), 7.56 (1H, d, 8.2 Hz), 7.22 (1H, s), 7.04 (1H, d, 9.0 Hz), 3.77-3.75 (4H, m), 3.35-3.30 (4H, m), 1.74 (6H, s)

[1146] LCMS: m/z 372 [M+H].sup.+

[1147] HPLC retention time: 2.45 min (analysis condition U)

Example 93

Compound B2-4

6,6-Dimethyl-11-oxo-8-(4-pyrrolidin-1-yl-piperidin-1-yl)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1148] ##STR00108##

[1149] Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound B1 and 4-pyrrolidin-1-yl-piperidine.

[1150] .sup.1H-NMR (270 MHz, DMSO-d.sub.6) : 8.30 (1H, d, 8.1 Hz), 8.01 (1H, d, 8.7 Hz), 7.97 (1H, s), 7.56 (1H, d, 8.6 Hz), 7.20 (1H, s), 3.94-3.90 (2H, m), 3.30-3.28 (4H, m), 2.95 (2H, t, 11.8 Hz), 2.24-2.20 (1H, m), 1.95-1.91 (2H, m), 1.75 (6H, s), 1.70-1.66 (4H, m), 1.54-1.52 (2H, m)

[1151] LCMS: m/z 439 [M+H].sup.+

Example 94

Compound B2-5-1

4-(3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl)-piperazine-1-carboxylic Acid Tert-Butyl Ester

[1152] ##STR00109##

[1153] Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound B1 and piperazine-1-carboxylic acid tert-butyl ester.

[1154] LCMS: m/z 471 [M+H].sup.+

[1155] HPLC retention time: 2.67 min (analysis condition S)

Example 95

Compound B2-5-2

6,6-Dimethyl-11-oxo-8-piperazin-1-yl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1156] ##STR00110##

[1157] Under the same conditions as the method for synthesizing Compound A8-1, the title compound was prepared from Compound B2-5-1.

[1158] .sup.1H-NMR (400 MHz, DMSO-d.sub.6) : 8.32 (1H, d, 8.5 Hz), 8.03 (1H, d, 9.1 Hz), 7.99 (1H, s), 7.59 (1H, dd, 8.2, 1.5 Hz), 7.20 (1H, d, 2.4 Hz), 7.04 (1H, dd, 8.8, 2.1 Hz), 3.32-3.30 (4H, m), 2.88-2.87 (4H, m), 1.77 (6H, s)

[1159] LCMS: m/z 371 [M+H].sup.+

Example 96

Compound B2-6

6,6-Dimethyl-11-oxo-8-piperidin-1-yl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1160] ##STR00111##

[1161] Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound B1 and piperidine.

[1162] LCMS: m/z 370 [M+H].sup.+

[1163] HPLC retention time: 2.40 min (analysis condition U)

Example 97

Compound B2-7-1

8-(4-Hydroxy-piperidin-1-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1164] ##STR00112##

[1165] Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound B1 and piperidin-4-ol.

[1166] .sup.1H-NMR (270 MHz, DMSO-d.sub.6) : 8.30 (1H, d, 8.1 Hz), 8.01 (1H, d, 8.7 Hz), 7.97 (1H, s), 7.56 (1H, d, 7.7 Hz), 7.19 (1H, s), 7.04 (1H, d, 10.6 Hz), 4.76-4.71 (1H, br m), 3.81-3.75 (3H, m), 3.08 (2H, t, 10.2 Hz), 1.86-1.82 (2H, m), 1.75 (6H, s), 1.49-1.42 (2H, m)

[1167] LCMS: m/z 386 [M+H].sup.+

Example 98

Compound B2-7-2

6,6-Dimethyl-11-oxo-8-(4-oxo-piperidin-1-yl)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1168] ##STR00113##

[1169] 8-(4-Hydroxy-piperidin-1-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (Compound B2-7-1, 210 mg, 0.545 mmol), was dissolved in the DCM (2 mL) and DMF (0.6 mL) mixture solvent, added with 1,1,1-triacetoxy-1,1-dihydro-1,2-benzoiodoxol-3(1H)-one (300 mg, 1.3 eq.), and the mixture was stirred at room temperature for 2 hr. To the reaction solution, 0.25 mol/L aqueous solution of sodium thiosulfate, saturated sodium bicarbonate solution and CPME were added followed by further stirring at room temperature for 1 hr. The reaction solution was filtered and the filtrate was subjected to liquid separation. The organic layer was washed with saturated brine and dried over sodium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain the target compound (yellowish white powder, 109 mg, 52%).

[1170] LCMS: m/z 384 [M+H].sup.+

[1171] HPLC retention time: 2.17 min (analysis condition U)

Example 99

Compound B2-8

8-(4-Methanesulfonyl-piperazin-1-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1172] ##STR00114##

[1173] Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound B1 and 1-methanesulfonylpiperazine.

[1174] .sup.1H-NMR (270 MHz, DMSO-d.sub.6) : 12.66 (1H, br. s), 8.31 (1H, d, J=8.2 Hz), 8.06 (1H, d, J=8.7 Hz), 7.99 (1H, s), 7.59 (1H, d, J=8.2 Hz), 7.30 (1H, d, J=1.8 Hz), 7.09 (1H, dd, J=8.7, 1.8 Hz), 3.53 (4H, t, J=4.8 Hz), 3.27 (4H, t, J=4.8 Hz), 2.94 (3H, s), 1.77 (6H, s).

[1175] LCMS: m/z 449 [M+H].sup.+

[1176] HPLC retention time: 1.98 min (analysis condition S)

Example 100

Compound B2-9

8-(3-Methanesulfonyl-pyrrolidin-1-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1177] ##STR00115##

[1178] Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound B1 and 3-methanesulfonylpyrrolidine.

[1179] LCMS: m/z 434 [M+H].sup.+

[1180] HPLC retention time: 1.83 min (analysis condition S)

Example 101

Compound B2-10

8-(1,1-Dioxothiomorpholino)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1181] ##STR00116##

[1182] Trifluoro-methanesulfonic acid 3-cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl ester (Compound B1, 30 mg, 0.069 mmol) was dissolved in 1,4-dioxane (1 mL), added with thiomorpholine 1,1-dioxide (19 mg, 2 eq.), Pd.sub.2 (dba).sub.3 (6.3 mg, 0.1 eq.), BINAP (8.6 mg, 0.2 eq.) and K.sub.3PO.sub.4 (29 mg, 2 eq.), and stirred at 100 C. overnight. The reaction solution was added to water, and then extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over sodium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain the target compound (white powder, 2.1 mg, 7%).

[1183] .sup.1H-NMR (270 MHz, DMSO-d.sub.6) : 8.29 (1H, d, J=8.6 Hz), 8.07 (1H, d, J=8.9 Hz), 8.00 (1H, s), 7.55 (1H, dd, J=8.5, 1.7 Hz), 7.34 (1H, d, J=2.0 Hz), 7.15 (1H, dd, J=9.1, 2.7 Hz), 4.01 (4H, s), 3.16 (4H, s), 1.77 (6H, s).

[1184] LCMS: m/z 420 [M+H].sup.+

[1185] HPLC retention time: 1.80 min (analysis condition S)

Example 102

Compound B2-11

8-(4-Cyclopentyl-2-oxo-piperazin-1-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1186] ##STR00117##

[1187] Under the same conditions as the method for synthesizing Compound B2-10, the title compound was prepared from Compound B1 and 4-cyclopentylpiperazin-2-one.

[1188] LCMS: m/z 453 [M+H].sup.+

[1189] HPLC retention time: 1.30 min (analysis condition S)

Example 103

Compound B2-12

6,6-Dimethyl-8-(4-morpholin-4-yl-piperidin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1190] ##STR00118##

[1191] Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound B1 and 4-piperidin-4-yl morpholine.

[1192] .sup.1H-NMR (400 MHz, DMSO-d.sub.6) : 12.73 (1H, s), 8.27-8.31 (1H, m), 7.98-8.02 (1H, m), 7.95-7.97 (1H, m), 7.53-7.58 (1H, m), 7.17-7.21 (1H, m), 6.99-7.05 (1H, m), 3.97-4.05 (2H, m), 3.53-3.59 (4H, m), 2.80-2.90 (2H, m), 2.43-2.51 (4H, m), 2.31-2.40 (1H, m), 1.83-1.92 (2H, m), 1.74 (6H, s), 1.39-1.52 (2H, m)

[1193] LCMS: m/z 455 [M+H].sup.+

[1194] HPLC retention time: 1.73 min (analysis condition U)

Example 104

Compound B2-13

8-(4,4-Difluoro-1,4-bipiperidin-1-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1195] ##STR00119##

[1196] Under the same conditions as the method for synthesizing Compound B3-32, the title compound was prepared from Compound B2-7-2 and 4,4-difluoropiperidine hydrochloric acid salt.

[1197] .sup.1H-NMR (400 MHz, DMSO-d.sub.6) : 12.59 (1H, s), 8.25-8.32 (1H, m), 7.97-8.02 (1H, m), 7.96 (1H, s), 7.52-7.59 (1H, m), 7.16-7.21 (1H, m), 6.99-7.05 (1H, mz), 4.00-4.09 (2H, m), 3.55-3.62 (2H, m), 2.79-2.90 (2H, m), 2.55-2.67 (4H, m), 1.78-1.98 (5H, m), 1.74 (6H, s), 1.44-1.58 (2H, m)

[1198] LCMS: m/z 489 [M+H].sup.+

[1199] HPLC retention time: 1.88 min (analysis condition U)

Example 105

Compound B2-14

8-[4-((2R,6S)-2,6-Dimethyl-morpholin-4-yl)-piperidin-1-yl]-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1200] ##STR00120##

[1201] Under the same conditions as the method for synthesizing Compound B3-32, the title compound was prepared from Compound B2-7-2 and (2R,6S)-2,6-dimethylmorpholine.

[1202] .sup.1H-NMR (400 MHz, DMSO-d.sub.6) : 12.60 (1H, s), 8.25-8.31 (1H, m), 7.97-8.02 (1H, m), 7.95 (1H, s), 7.51-7.58 (1H, m), 7.18 (1H, s), 6.99-7.05 (1H, m), 3.96-4. 06 (2H, m), 3.45-3.55 (2H, m), 2.80-2.91 (2H, m), 2.72-2.79 (2H, m), 2.29-2.41 (1H, m), 1.70-1.90 (10H, m), 1.40-1.53 (2H, m), 1.03 (6H, d, 6.3 Hz)

[1203] LCMS: m/z 483 [M+H].sup.+

[1204] HPLC retention time: 1.83 min (analysis condition U)

Example 106

Compound B2-15

8-((3R,5S)-3,5-Dimethylpiperazin-1-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1205] ##STR00121##

[1206] Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound B1 and 2,6-dimethylpiperazine.

[1207] LCMS: m/z 399 [M+H].sup.+

[1208] HPLC retention time: 1.76 min (analysis condition U)

Example 107

Compound B2-16-1

(S)-4-(3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl)-3-methyl-piperazine-1-carboxylic Acid Tert-Butyl Ester

[1209] ##STR00122##

[1210] Under the same conditions as the method for synthesizing Compound B2-10, the title compound was prepared from Compound B1 and (S)-3-methylpiperazine-1-carboxylic acid tert-butyl ester.

[1211] LCMS: m/z 485 [M+H].sup.+

[1212] HPLC retention time: 3.97 min (analysis condition W)

Example 108

Compound B2-16-2

6,6-Dimethyl-8-((S)-2-methyl-piperazin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1213] ##STR00123##

[1214] Under the same conditions as the method for synthesizing Compound A8-1, the title compound was prepared from Compound 2-16-1.

[1215] LCMS: m/z 385 [M+H].sup.+

[1216] HPLC retention time: 2.43 min (analysis condition W)

Example 109

Compound B2-16-3

8-((S)-4-Cyclobutyl-2-methyl-piperazin-1-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1217] ##STR00124##

[1218] Under the same conditions as the method for synthesizing Compound B3-32, the title compound was prepared from Compound B2-16-2 and cyclobutanone.

[1219] .sup.1H-NMR (400 MHz, DMSO-d.sub.6) : 8.31 (1H, d, 8 Hz), 8.03 (1H, d, 12 Hz), 7.98 (1H, s), 7.59 (1H, d, 12 Hz), 7.13 (1H, s), 6.98 (1H, d, 8 Hz), 4.35-4.28 (1H, m), 3.70 (1H, d, 12 Hz), 3.02 (1H, ddd, 12, 12, 4 Hz), 2.87 (1H, d, 8 Hz), 2.74-2.67 (2H, m), 2.08-1.99 (2H, m), 1.92-1.64 (10H, m), 1.70-1.62 (2H, m), 1.12 (3H, d, 8 Hz)

[1220] LCMS: m/z 439 [M+H].sup.+

[1221] HPLC retention time: 2.59 min (analysis condition W)

Example 110

Compound B2-17

8-(2-Diethylamino-ethylsulfanyl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1222] ##STR00125##

[1223] Trifluoro-methanesulfonic acid 3-cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl ester (Compound B1, 25 mg, 0.057 mmol) was dissolved in dimethoxyethane (0.5 mL), added with 2-diethylaminoethanethiol hydrochloric acid salt (19.6 mg, 2 eq.), Pd.sub.2(dba).sub.3(2.6 mg, 0.05 eq.), Xantphos (3.3 mg, 0.1 eq.) and DIPEA (0.06 mg, 6 eq.), and the mixture was stirred at 160 C. for 30 min. The reaction solution was added to water, extracted with ethyl acetate, and dried over magnesium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (dichloromethane/methanol) to obtain the target compound (white amorphous, 22.4 mg, 93%).

[1224] .sup.1H-NMR (400 MHz, CDCl.sub.3) : 9.60 (1H, s), 8.53-8.48 (1H, m), 8.32 (1H, d, J=8.4 Hz), 7.77 (1H, s), 7.53-7.50 (2H, m), 7.38-7.35 (1H, m), 3.18-3.12 (2H, m), 2.81-2.75 (2H, m), 2.65-2.57 (4H, m), 1.76 (6H, s), 1.08-1.04 (6H, m)

[1225] LCMS: m/z 418 [M+H].sup.+

[1226] HPLC retention time: 2.10 min (analysis condition U)

Example 111

Compound B2-18

8-(2-Diisopropylamino-ethylsulfanyl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1227] ##STR00126##

[1228] Under the same conditions as the method for synthesizing Compound B2-17, the title compound was prepared from Compound B1 and 2-diisopropylaminoethanethiol hydrochloric acid salt.

[1229] LCMS: m/z 446 [M+H].sup.+

[1230] HPLC retention time: 2.22 min (analysis condition U)

Example 112

Compound B2-19

8-(2-Dimethylamino-ethylsulfanyl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1231] ##STR00127##

[1232] Under the same conditions as the method for synthesizing Compound B2-17, the title compound was prepared from Compound B1 and 2-dimethylaminoethanethiol hydrochloric acid salt.

[1233] LCMS: m/z 390 [M+H].sup.+

[1234] HPLC retention time: 1.98 min (analysis condition U)

Example 113

Compound B2-20

3-(3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl sulfanyl)-propionic Acid

[1235] ##STR00128##

[1236] Under the same conditions as the method for synthesizing Compound B2-17, the title compound was prepared from Compound B1 and 3-mercaptopropionic acid.

[1237] LCMS: m/z 391 [M+H].sup.+

[1238] HPLC retention time: 2.45 min (analysis condition U)

Example 114

Compound B2-21

8-(2,3-Dihydroxy-propylsulfanyl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1239] ##STR00129##

[1240] Under the same conditions as the method for synthesizing Compound B2-17, the title compound was prepared from Compound B1 and 3-mercaptopropane-1,2-diol.

[1241] LCMS: m/z 393 [M+H].sup.+

[1242] HPLC retention time: 2.15 min (analysis condition U)

Example 115

Compound B2-22-1

4-(3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl)-3,6-dihydro-2H-pyridine-1-carboxylic Acid Tert-Butyl Ester

[1243] ##STR00130##

[1244] To trifluoro-methanesulfonic acid 3-cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl ester (Compound B1, 7.80 g, 18.0 mmol), 4-(4,4,5,5-tetramethyl-[1,3,2] dioxaborolan-2-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (6.11 g, 19.8 mmol, 1.1 eq.), Pd(PPh.sub.3).sub.2Cl.sub.2 (630 mg, 0.898 mmol, 0.05 eq.), and sodium carbonate (5.71 g, 53.9 mmol, 3.0 eq.), DME (125 ml) and water (25 ml) were added. The mixture was subjected to reduced pressure under ultrasonication treatment, followed by flushing with nitrogen gas. This procedure was repeated five times and then degassed. After further stirring at 80 C. for 2 hr under nitrogen atmosphere, the mixture was cooled to room temperature, added with water (250 ml), and further stirred for 30 min. The precipitates were filtered and washed with water (50 ml). They were further washed with CH.sub.3CN (50 ml) to obtain the target compound as a crude product (gray powder, 7.54 g, 90%).

[1245] LCMS: m/z 468 [M+H].sup.+

[1246] HPLC retention time: 2.90 min (analysis condition S)

Example 116

Compound B2-22-2

6,6-Dimethyl-11-oxo-8-(1,2,3,6-tetrahydro-pyridin-4-yl)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1247] ##STR00131##

[1248] Under the same conditions as the method for synthesizing Compound A8-1, the title compound was prepared from Compound B2-22-1.

[1249] LCMS: m/z 368 [M+H].sup.+

[1250] HPLC retention time: 1.47 min (analysis condition S)

Example 117

Compound B2-23

6,6-Dimethyl-8-(1-methyl-1H-pyrazol-4-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1251] ##STR00132##

[1252] Under the same conditions as the method for synthesizing Compound B2-22-1, the title compound was prepared from Compound B1 and 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole.

[1253] LCMS: m/z 367 [M+H].sup.+

[1254] HPLC retention time: 2.42 min (analysis condition U)

Example 118

Compound B2-24

6,6-Dimethyl-11-oxo-8-vinyl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1255] ##STR00133##

[1256] Under nitrogen atmosphere, trifluoro-methanesulfonic acid 3-cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl ester (Compound B1, 1.00 g, 2.302 mmol) was added with n-propanol (20 mL), potassium vinyltrifluoroborate (854 mg, 3.0 eq.), dichloro-((bis-diphenylphosphino)ferrocenyl)palladium (217 mg, 0.1 eq.) and triethylamine (1.11 ml, 3.0 eq.) in order and the resultant was stirred at 60 C. for 4 hr. Upon the completion of the reaction, water was added to the reaction solution. The resulting precipitates were filtered and washed with distilled water, and the residues were dried to obtain the title compound (666 mg, 80%).

[1257] .sup.1H-NMR (400 MHz, CDCl.sub.3) : 8.90 (1H, s), 8.55 (1H, d, J=7.9 Hz), 8.40 (1H, d, J=8.5 Hz), 7.79 (1H, s), 7.58-7.61 (3H, m), 6.85 (1H, dd, J=17.7, 11.0 Hz), 5.95 (1H, d, J=17.1 Hz), 5.46 (1H, d, J=11.0 Hz), 1.84 (6H, s)

[1258] LCMS: m/z 313 [M+H].sup.+

[1259] HPLC retention time: 3.75 min (analysis condition W)

Example 119

Compound B2-25-1

4-(3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl methyl)-piperidine-1-carboxylic Acid Tert-Butyl Ester

[1260] ##STR00134##

[1261] 4-Methylene-piperidine-1-carboxylic acid tert-butyl ester (409 mg, 2.07 mmol, 1.2 eq.) was dissolved in THF (2 ml), added under nitrogen atmosphere with 9-BBN (0.5 M THF solution, 4.83 ml, 2.42 mmol, 1.4 eq.) and then stirred at 60 C. for 1 hr. Thereafter, 9-BBN (0.5 M THF solution, 5.52 ml, 2.77 mmol, 1.6 eq.) was further added and the mixture was stirred at 60 C. for 1 hr. The resulting mixture was cooled to room temperature, added with cesium fluoride (1.31 g, 8.60 mmol, 5.0 eq.), and stirred at room temperature for 30 min.

[1262] To the solution obtained from the above, DMF (18 ml) suspension comprising trifluoro-methanesulfonic acid 3-cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl ester (Compound B1, 750 mg, 1.73 mmol) and dichloro-((bisdiphenylphosphino)ferrocenyl)palladium (70.5 mg, 0.0863 mmol, 0.05 eq.) was added, and the mixture was stirred at 100 C. for 3 hr. After cooling to the room temperature, water (50 ml) was added, followed by extraction with ethyl acetate. The organic layer was washed with saturated brine and dried over sodium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain 4-(3-cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl methyl)-piperidine-1-carboxylic acid tert-butyl ester (yellow powder, 763 mg, 91%).

[1263] LCMS: m/z 484 [M+H].sup.+

[1264] HPLC retention time: 2.97 min (analysis condition S)

Example 120

Compound B2-25-2

6,6-Dimethyl-11-oxo-8-piperidin-4-yl methyl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1265] ##STR00135##

[1266] Under the same conditions as the method for synthesizing Compound A8-1, the title compound was prepared from Compound B2-25-1.

[1267] LCMS: m/z 384 [M+H].sup.+

[1268] HPLC retention time: 1.40 min (analysis condition S)

Example 121

Compound B2-26-1

Tert-butyl 4-((3-cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl)methyl)piperidin-1-yl sulfonylcarbamic Acid

[1269] ##STR00136##

[1270] Under the same conditions as the method for synthesizing Compound A9-1, the title compound was prepared from Compound B2-25-2 and N-(tert-butoxycarbonyl)-N-[4-(dimethylazaniumylidene)-1,4-dihydropyridin-1-yl sulfonyl]azanide (CAS No. 872496-91-8).

[1271] LCMS: m/z 563 [M+H].sup.+

[1272] HPLC retention time: 2.63 min (analysis condition S)

Example 122

Compound B2-26-2

4-(3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl methyl)-piperidine-1-sulfonic Acid Amide

[1273] ##STR00137##

[1274] Under the same conditions as the method for synthesizing Compound A8-1, the title compound was prepared from Compound B2-26-1.

[1275] LCMS: m/z 463 [M+H].sup.+

[1276] HPLC retention time: 2.10 min (analysis condition S)

Example 123

Compound B2-27

8-(1-Isopropyl-piperidin-4-yl methyl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1277] ##STR00138##

[1278] Under the same conditions as the method for synthesizing Compound B3-32, the title compound was prepared from Compound B2-25-2 and acetone.

[1279] .sup.1H-NMR (400 MHz, DMSO-d.sub.6) : 12.80 (1H, s), 8.32 (1H, d, 7.9 Hz), 8.12 (1H, d, 7.9 Hz), 8.01 (1H, s), 7.65 (1H, s), 7.61 (1H, d, 9.1 Hz), 7.30 (1H, d, 7.9 Hz), 2.75 (2H, d, 11.0 Hz), 2.65 (3H, q, 6.5 Hz), 2.04 (2H, t, 11.0 Hz), 1.77 (6H, s), 1.60-1.57 (3H, m), 1.22 (2H, t, 11.6 Hz), 0.94 (6H, d, 6.7 Hz)

[1280] LCMS: m/z 426 [M+H].sup.+

Example 124

Compound B2-28

3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-carboxylic Acid

[1281] ##STR00139##

[1282] Under nitrogen atmosphere, to the dimethyl formamide (3 ml) solution comprising trifluoro-methanesulfonic acid 3-cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl ester (Compound B1, 150 mg, 0.345 mmol), lithium formate monohydrate (90 mg, 5.0 eq.), 4,5-bis (diphenylphosphino)-9,9-dimethylxanthene (Xantphos) (20 mg, 0.1 eq.), Pd.sub.2(dba).sub.3 (32 mg, 0.1 eq.), lithium chloride (88 mg, 6.0 eq.), N,N-diisopropylethylamine (241 l, 4.0 eq.), and acetic anhydride (131 l, 4.0 eq.) were added, and the mixture was stirred at 80 C. for 15 hr. Upon the completion of the reaction, ethyl acetate was added to the reaction solution. The organic layer was washed in order with 1 M hydrochloric acid, distilled water, and brine. The organic layer was dried over sodium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain the title compound (88 mg, 76%).

[1283] .sup.1H-NMR (400 MHz, DMSO-d.sub.6) : 13.17 (1H, s), 8.35 (1H, d, J=7.9 Hz), 8.34 (1H, s), 8.23 (1H, d, J=7.9 Hz), 8.07 (1H, s), 8.02 (1H, d, J=9.1 Hz), 7.64 (1H, d, J=7.9 Hz), 1.80 (6H, s)

[1284] LCMS: m/z 331 [M+H].sup.+

[1285] HPLC retention time: 3.08 min (analysis condition W)

Example 125

Compound B2-29

8-Formyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1286] ##STR00140##

[1287] To the THF (24 ml) and distilled water (6 ml) suspension of 6,6-dimethyl-11-oxo-8-vinyl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (Compound B2-24, 600 mg, 1.920 mmol), t-butanol solution of osmium tetraoxide (192 l, 0.1 eq.) and sodium meta periodate (821 mg, 2.0 eq.) were added and the mixture was stirred at room temperature for 3 hr. Aqueous solution of sodium thiosulfate (0.3 M) was added to the solution, which was then extracted with an ethyl acetate. The organic layer was washed with 10% aqueous solution of disodium ethylenediamine tetraacetic acid. The organic layer was dried over sodium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain the title compound (470 mg, 77%).

[1288] .sup.1H-NMR (400 MHz, DMSO-d.sub.6) : 12.95 (1H, s), 10.20 (1H, s), 8.48 (1H, s), 8.42 (1H, d, J=8.5 Hz), 8.36 (1H, d, J=8.5 Hz), 8.07 (1H, s), 8.02 (1H, d, J=7.9 Hz), 7.67 (1H, d, J=7.9 Hz), 1.85 (6H, s)

[1289] LCMS: m/z 315 [M+H].sup.+

[1290] HPLC retention time: 3.38 min (analysis condition W)

Example 126

Compound B3-1

5,6,6-Trimethyl-8-morpholin-4-yl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1291] ##STR00141##

[1292] Under the same conditions as the method for synthesizing Compound A10-1, the title compound was prepared from Compound B2-3.

[1293] LCMS: m/z 386 [M+H].sup.+

[1294] HPLC retention time: 2.62 min (analysis condition U)

Example 127

Compound B3-2-1

Tert-butyl 4-(3-cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl)piperazin-1-yl sulfonylcarbamic Acid

[1295] ##STR00142##

[1296] Under the same conditions as the method for synthesizing Compound A9-1, the title compound was prepared from Compound B2-5-2 and N-(tert-butoxycarbonyl)-N-[4-(dimethylazaniumylidene)-1,4-dihydropyridin-1-yl sulfonyl]azanide (CAS No. 872496-91-8).

[1297] LCMS: m/z 550 [M+H].sup.+

[1298] HPLC retention time: 2.39 min (analysis condition S)

Example 128

Compound B3-2-2

4-(3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl)-piperazine-1-sulfonic Acid Amide

[1299] ##STR00143##

[1300] Under the same conditions as the method for synthesizing Compound A8-1, the title compound was prepared from Compound B3-2-1.

[1301] LCMS: m/z 450 [M+H].sup.+

[1302] HPLC retention time: 1.82 min (analysis condition S)

Example 129

Compound B3-3

4-(3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl)-piperazine-1-sulfonic Acid Dimethylamide

[1303] ##STR00144##

[1304] Under the same conditions as the method for synthesizing Compound A9-1, the title compound was prepared from Compound B2-5-2 and dimethylsulfamoyl chloride.

[1305] LCMS: m/z 478 [M+H].sup.+

[1306] HPLC retention time: 2.45 min (analysis condition S)

Example 130

Compound B3-4

4-(3-Cyano-5,6,6-trimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl)-piperazine-1-sulfonic Acid Dimethylamide

[1307] ##STR00145##

[1308] To the DMF suspension of 4-(3-cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl)-piperazine-1-sulfonic acid amide (Compound B3-2-2, 20 mg, 0.04 mmol) and sodium hydride (21.4 mg, 12 eq.), iodomethane (28 l, 10 eq.) was added and stirred at room temperature overnight. Water was added to the reaction solution, followed by filtration to obtain the target compound (25.8 mg, 100%).

[1309] .sup.1H-NMR (270 MHz, DMSO-d.sub.6) : 8.43 (1H, d, J=8.2 Hz), 8.31 (1H, s), 8.03 (1H, d, J=8.9 Hz), 7.64 (1H, dd, J=8.1, 1.3 Hz), 7.30 (1H, d, J=2.0 Hz), 7.08 (1H, dd, J=8.9, 2.0 Hz), 4.16 (3H, s), 3.43-3.53 (4H, t, J=4.7 Hz), 3.26-3.41 (4H, s), 2.82 (6H, s), 1.87 (6H, s).

[1310] LCMS: m/z 492 [M+H].sup.+

[1311] HPLC retention time: 2.69 min (analysis condition S)

Example 131

Compound B3-5

8-(4-Cyclopropyl-piperazin-1-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1312] ##STR00146##

[1313] The title compound was obtained as a by-product of the synthesis of Compound F5-36.

[1314] LCMS: m/z 411 [M+H].sup.+

[1315] HPLC retention time: 1.31 min (analysis condition S)

Example 132

Compound B3-6

8-(4-Cyclobutyl-piperazin-1-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1316] ##STR00147##

[1317] Under the same conditions as the method for synthesizing Compound B3-32, the title compound was prepared from Compound B2-5-2 and cyclobutanone.

[1318] .sup.1H-NMR (400 MHz, DMSO-d.sub.6) : 8.29 (1H, d, J=8.2 Hz), 8.01 (1H, d, J=8.8 Hz), 7.96 (1H, s), 7.55 (1H, d, J=8.2 Hz), 7.19 (1H, d, J=2.2 Hz), 7.03 (1H, dd, J=2.4, 8.8 Hz), 2.71-2.75 (1H, m), 2.37-2.39 (4H, m), 1.98-2.00 (2H, m), 1.77-1.85 (2H, m), 1.74 (6H, s), 1.63-1.68 (2H, m).

[1319] LCMS: m/z 425 [M+H].sup.+

[1320] HPLC retention time: 1.80 min (analysis condition U)

Example 133

Compound B3-7

6,6-Dimethyl-8-(4-oxetan-3-yl-piperazin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1321] ##STR00148##

[1322] Under the same conditions as the method for synthesizing Compound B3-32, the title compound was prepared from Compound B2-5-2 and 3-oxetanone.

[1323] .sup.1H-NMR (400 MHz, DMSO-d.sub.6) : 8.29 (1H, dd, J=8.2, 0.59 Hz), 8.02 (1H, d, J=9.0 Hz), 7.97 (1H, d, J=0.59 Hz), 7.56 (1H, dd, J=8.0, 1.4 Hz), 7.22 (1H, d, J=2.3 Hz), 7.04 (1H, dd, J=8.8, 2.2 Hz), 4.56-4.59 (2H, m), 4.47-4.50 (2H, m), 3.43-3.48 (1H, m), 3.39-3.42 (4H, m), 2.40-2.42 (4H, m), 1.74 (6H, s)

[1324] LCMS: m/z 427 [M+H].sup.+

[1325] HPLC retention time: 1.67 min (analysis condition U)

Example 134

Compound B3-8

8-(2-Diethylamino-ethanesulfonyl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1326] ##STR00149##

[1327] 8-(2-Diethylamino-ethylsulfanyl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (Compound B2-17, 16.8 mg, 0.0402 mmol) was dissolved in methanol (1.5 mL), added with oxone (54.3 mg, 2.2 eq.) which had been dissolved in water (0.5 mL), and then stirred at room temperature for 2 hr. The reaction solution was concentrated, extracted with ethyl acetate, washed with saturated sodium hydrogen carbonate, and dried over magnesium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (dichloromethane/methanol) to obtain the target compound (white solid, 5.8 mg, 32%).

[1328] .sup.1H-NMR (400 MHz, CDCl.sub.3) : 9.29 (1H, s), 8.61 (1H, d, J=8.2 Hz), 8.52 (1H, d, J=8.0 Hz), 8.21 (1H, s), 8.01 (1H, d, J=8.2 Hz), 7.81 (1H, s), 7.61 (1H, d, J=8.2 Hz), 3.33 (2H, t, J=7.4 Hz), 2.95 (2H, t, J=7.4 Hz), 2.41 (4H, q, J=7.2 Hz), 1.86 (6H, s), 0.89 (4H, t, J=7.1 Hz)

[1329] LCMS: m/z 450 [M+H].sup.+

[1330] HPLC retention time: 2.05 min (analysis condition U)

Example 135

Compound B3-9

8-(2-Diisopropylamino-ethanesulfonyl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1331] ##STR00150##

[1332] Under the same conditions as the method for synthesizing Compound B3-8, the title compound was prepared from Compound B2-18.

[1333] LCMS: m/z 478 [M+H].sup.+

[1334] HPLC retention time: 2.18 min (analysis condition U)

Example 136

Compound B3-10

8-(2-Dimethylamino-ethanesulfonyl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1335] ##STR00151##

[1336] Under the same conditions as the method for synthesizing Compound B3-8, the title compound was prepared from Compound B2-19.

[1337] LCMS: m/z 422 [M+H].sup.+

[1338] HPLC retention time: 2.03 min (analysis condition U)

Example 137

Compound B3-11

3-(3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-sulfonyl)-propionic Acid

[1339] ##STR00152##

[1340] Under the same conditions as the method for synthesizing Compound B3-8, the title compound was prepared from Compound B2-20.

[1341] LCMS: m/z 423 [M+H].sup.+

[1342] HPLC retention time: 2.28 min (analysis condition U)

Example 138

Compound B3-12

8-(2,3-Dihydroxy-propane-1-sulfonyl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1343] ##STR00153##

[1344] Under the same conditions as the method for synthesizing Compound B3-8, the title compound was prepared from Compound B2-21.

[1345] LCMS: m/z 425 [M+H].sup.+

[1346] HPLC retention time: 2.17 min (analysis condition U)

Example 139

Compound B3-13-1

4-(3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl)-piperidine-1-carboxylic acid tert-butyl ester

[1347] ##STR00154##

[1348] 4-(3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (Compound B2-22-1, 16.2 g, 34.6 mmol) was dissolved in THF (800 ml) and methanol (230 ml), added with 10 wt % Pd/C (3.2 g), and stirred under hydrogen atmosphere for 19 hr. The solid was filtered through Celite, eluted with a mixture solvent (400 ml; THF/methanol=4/1), and concentrated under reduced pressure. The residues were dissolved in ethyl acetate (400 ml), and then washed with 1% aqueous solution of N-acetylcysteine, saturated aqueous solution of NaHCO.sub.3 and saturated brine. The organic layer was dried over sodium sulfate. The drying agent was removed by filtration and the residues were concentrated under reduced pressure to obtain the title compound as a crude product (white powder, 14.0 g, 86%).

[1349] LCMS: m/z 470 [M+H].sup.+

[1350] HPLC retention time: 2.88 min (analysis condition S)

Example 140

Compound B3-13-2

6,6-Dimethyl-11-oxo-8-piperidin-4-yl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1351] ##STR00155##

[1352] Under the same conditions as the method for synthesizing Compound A8-1, the title compound was prepared from Compound B3-13-1.

[1353] LCMS: m/z 370 [M+H].sup.+

[1354] HPLC retention time: 1.30 min (analysis condition S)

Example 141

Compound B3-14

8-(1,2-Dihydroxy-ethyl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1355] ##STR00156##

[1356] To the THF (1 ml) solution of 6,6-dimethyl-11-oxo-8-vinyl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (Compound B2-24, 20 mg, 0.064 mmol), t-butanol solution of osmium tetraoxide (19 l, 0.3 eq.) and 50% aqueous solution of N-methylmorpholine-N-oxide (30 l, 2.0 eq.) were added and the mixture was stirred at room temperature for 3 hr. To the reaction solution, 10% aqueous solution of disodium ethylenediamine tetraacetic acid was added, followed by extraction with ethyl acetate. The organic layer was dried over sodium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were purified by high performance liquid chromatography to obtain the title compound (21 mg, 63%).

[1357] .sup.1H-NMR (400 MHz, CD.sub.3OD) : 8.41 (1H, d, J=7.9 Hz), 8.29 (1H, d, J=7.9 Hz), 7.87 (1H, s), 7.86 (1H, s), 7.57 (1H, d, J=7.9 Hz), 7.52 (1H, d, J=6.7 Hz), 4.85 (1H, dd, J=7.0, 4.6 Hz), 3.73 (1H, dd, J=11.3, 4.6 Hz), 3.68 (1H, dd, J=11.3, 7.0 Hz), 1.83 (6H, s)

[1358] LCMS: m/z 347 [M+H].sup.+

[1359] HPLC retention time: 2.68 min (analysis condition W)

Example 142

Compound B3-15

6,6-Dimethyl-8-(morpholine-4-carbonyl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1360] ##STR00157##

[1361] To the tetrahydrofuran (1 ml) solution of 3-cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-carboxylic acid (Compound B2-28, 15 mg, 0.045 mmol), morpholine (6 l, 1.5 eq.), hexafluorophosphoric acid uronium 2-(1H-7-azabenzotriazol-1-yl)-1,1,3,3-tetramethylmethane aminium (HATU) (26 mg, 1.5 eq.), and N,N-diisopropylethylamine (24 l, 3.0 eq.) were added and the mixture was stirred at room temperature for 3 hr. The reaction solution was filtered to remove insoluble matters and the residues obtained after concentration under reduced pressure were purified by high performance liquid chromatography to obtain the title compound (11 mg, 55%).

[1362] .sup.1H-NMR (400 MHz, DMSO-d.sub.6) : 12.85 (1H, s), 8.33 (1H, d, J=8.5 Hz), 8.27 (1H, d, J=7.9 Hz), 8.03 (1H, s), 7.92 (1H, s), 7.63 (1H, d, J=8.5 Hz), 7.54 (1H, d, J=7.9 Hz), 3.52-3.77 (6H, m), 3.30-3.42 (2H, m), 1.79 (6H, s)

[1363] LCMS: m/z 400 [M+H].sup.+

[1364] HPLC retention time: 2.96 min (analysis condition W)

Example 143

Compound B3-16

8-(4-Methanesulfonyl-piperazin-1-carbonyl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1365] ##STR00158##

[1366] Under the same conditions as the method for synthesizing Compound B3-15, the title compound was prepared from Compound B2-28 and 1-methanesulfonylpiperazine.

[1367] LCMS: m/z 477 [M+H].sup.+

[1368] HPLC retention time: 3.03 min (analysis condition W)

Example 144

Compound B3-17

8-(4-Hydroxy-piperidin-1-carbonyl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1369] ##STR00159##

[1370] Under the same conditions as the method for synthesizing Compound B3-15, the title compound was prepared from Compound B2-28 and piperidin-4-ol.

[1371] LCMS: m/z 414 [M+H].sup.+

[1372] HPLC retention time: 2.75 min (analysis condition W)

Example 145

Compound B3-18

3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-carboxylic acid (2-hydroxy-1-hydroxymethyl-ethyl)-amide

[1373] ##STR00160##

[1374] Under the same conditions as the method for synthesizing Compound B3-15, the title compound was prepared from Compound B2-28 and 2-aminopropane-1,3-diol.

[1375] LCMS: m/z 404 [M+H].sup.+

[1376] HPLC retention time: 2.60 min (analysis condition W)

Example 146

Compound B3-19

3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-carboxylic acid (2-methanesulfonyl-ethyl)-amide

[1377] ##STR00161##

[1378] Under the same conditions as the method for synthesizing Compound B3-15, the title compound was prepared from Compound B2-28 and 2-methanesulfonylethylamine.

[1379] LCMS: m/z 436 [M+H].sup.+

[1380] HPLC retention time: 2.87 min (analysis condition W)

Example 147

Compound B3-20

3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-carboxylic acid (1,1-dioxo-tetrahydro-thiophen-3-yl)-amide

[1381] ##STR00162##

[1382] Under the same conditions as the method for synthesizing Compound B3-15, the title compound was prepared from Compound B2-28 and (1,1-dioxotetrahydrothiophen-3-yl)amine

[1383] LCMS: m/z 448 [M+H].sup.+

[1384] HPLC retention time: 1.70 min (analysis condition S)

Example 148

Compound B3-21

3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-carboxylic acid ((R)-2,3-dihydroxy-propyl)-amide

[1385] ##STR00163##

[1386] Under the same conditions as the method for synthesizing Compound B3-15, the title compound was prepared from Compound B2-28 and (R)-(+)-3-amino-1,2-propanediol.

[1387] LCMS: m/z 404 [M+H].sup.+

[1388] HPLC retention time: 1.38 min (analysis condition S)

Example 149

Compound B3-22

3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-carboxylic acid bis-(2-hydroxy-ethyl)-amide

[1389] ##STR00164##

[1390] Under the same conditions as the method for synthesizing Compound B3-15, the title compound was prepared from Compound B2-28 and N,N-diethanolamine.

[1391] LCMS: m/z 418 [M+H].sup.+

[1392] HPLC retention time: 1.35 min (analysis condition S)

Example 150

Compound B3-23

3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-carboxylic acid oxetan-3-yl amide

[1393] ##STR00165##

[1394] Under the same conditions as the method for synthesizing Compound B3-15, the title compound was prepared from Compound B2-28 and oxetan-3-yl amine.

[1395] LCMS: m/z 386 [M+H].sup.+

[1396] HPLC retention time: 1.63 min (analysis condition S)

Example 151

Compound B3-24

3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-carboxylic acid (2-hydroxy-ethoxy)-amide

[1397] ##STR00166##

[1398] Under the same conditions as the method for synthesizing Compound B3-15, the title compound was prepared from Compound B2-28 and 2-aminooxy-ethanol.

[1399] LCMS: m/z 390 [M+H].sup.+

[1400] HPLC retention time: 1.54 min (analysis condition S)

Example 152

Compound B3-25-1

2-[(3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-carbonyl)-amino]-ethyl}-carbamic Acid Tert-Butyl Ester

[1401] ##STR00167##

[1402] Under the same conditions as the method for synthesizing Compound B3-15, the title compound was prepared from Compound B2-28 and (2-amino-ethyl)-carbamic acid tert-butyl ester.

[1403] LCMS: m/z 473 [M+H].sup.+

[1404] HPLC retention time: 2.08 min (analysis condition S)

Example 153

Compound B3-25-2

3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-carboxylic acid (2-amino-ethyl)-amide

[1405] ##STR00168##

[1406] Under the same conditions as the method for synthesizing Compound A8-1, the title compound was prepared from Compound B3-25-1.

[1407] LCMS: m/z 373 [M+H].sup.+

[1408] HPLC retention time: 1.19 min (analysis condition S)

Example 154

Compound B3-25-3

3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-carboxylic Acid (2-Methanesulfonylamino-Ethyl)-Amide

[1409] ##STR00169##

[1410] Under the same conditions as the method for synthesizing Compound A9-1, the title compound was prepared from Compound B3-25-2.

[1411] LCMS: m/z 451 [M+H].sup.+

[1412] HPLC retention time: 1.62 min (analysis condition S)

Example 155

Compound B3-26

3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-carboxylic acid (2-hydroxy-ethyl)-methyl-amide

[1413] ##STR00170##

[1414] Under the same conditions as the method for synthesizing Compound B3-15, the title compound was prepared from Compound B2-28 and 2-methylamino-ethanol.

[1415] LCMS: m/z 388 [M+H].sup.+

[1416] HPLC retention time: 1.53 min (analysis condition S)

Example 156

Compound B3-27-1

Tert-butyl N-(2-(3-cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8carboxamide)ethyl)sulfamoylcarbamic Acid

[1417] ##STR00171##

[1418] Under the same conditions as the method for synthesizing Compound A9-1, the title compound was prepared from Compound B3-25-2 and N-(tert-butoxycarbonyl)-N-[4-(dimethylazaniumylidene)-1,4-dihydropyridin-1-yl sulfonyl]azanide (CAS No. 872496-91-8).

[1419] LCMS: m/z 552 [M+H].sup.+

[1420] HPLC retention time: 2.03 min (analysis condition S)

Example 157

Compound B3-27-2

3-Cyano-6,6-dimethyl-11-oxo-N-(2-(sulfamoylamino)ethyl)-6,11-dihydro-5H-benzo[b]carbazol-8-carboxamide

[1421] ##STR00172##

[1422] Under the same conditions as the method for synthesizing Compound A8-1, the title compound was prepared from Compound B3-27-1.

[1423] LCMS: m/z 452 [M+H].sup.+

[1424] HPLC retention time: 1.57 min (analysis condition S)

Example 158

Compound B3-28

8-[4-(2-Hydroxy-ethyl)-piperazin-1-carbonyl]-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1425] ##STR00173##

[1426] Under the same conditions as the method for synthesizing Compound B3-15, the title compound was prepared from Compound B2-28 and 2-piperazin-1-yl ethanol.

[1427] LCMS: m/z 443 [M+H].sup.+

[1428] HPLC retention time: 1.75 min (analysis condition U)

Example 159

Compound B3-29

8-(4-Tert-butyl-piperazin-1-carbonyl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1429] ##STR00174##

[1430] Under the same conditions as the method for synthesizing Compound B3-15, the title compound was prepared from Compound B2-28 and 1-tert-butylpiperazine.

[1431] LCMS: m/z 455 [M+H].sup.+

[1432] HPLC retention time: 1.88 min (analysis condition U)

Example 160

Compound B3-30

8-[4-(2-Methoxy-ethyl)-piperazin-1-carbonyl]-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1433] ##STR00175##

[1434] Under the same conditions as the method for synthesizing Compound B3-15, the title compound was prepared from Compound B2-28 and 1-(2-methoxyethyl)piperazine.

[1435] LCMS: m/z 457 [M+H].sup.+

[1436] HPLC retention time: 1.83 min (analysis condition U)

Example 161

Compound B3-31-1

4-(3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-carbonyl)-piperazine-1-carboxylic Acid Tert-Butyl Ester

[1437] ##STR00176##

[1438] Under the same conditions as the method for synthesizing Compound B3-15, the title compound was prepared from Compound B2-28 and piperazine-1-carboxylic acid tert-butyl ester.

[1439] LCMS: m/z 499 [M+H].sup.+

[1440] HPLC retention time: 2.63 min (analysis condition U)

Example 162

Compound B3-31-2

6,6-Dimethyl-11-oxo-8-(piperazin-1-carbonyl)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1441] ##STR00177##

[1442] Under the same conditions as the method for synthesizing Compound A8-1, the title compound was prepared from Compound B3-31-1.

[1443] LCMS: m/z 399 [M+H].sup.+

[1444] HPLC retention time: 1.78 min (analysis condition U)

Example 163

Compound B3-32

6,6-Dimethyl-8-morpholin-4-yl methyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1445] ##STR00178##

[1446] To the THF (1 ml) solution of Compound B2-29 (30 mg, 0.095 mmol), morpholine (6 l, 1.5 eq.) and sodium triacetoxyborohydride (81 mg, 2.0 eq.) were added and stirred at room temperature for 1 hr. The reaction solution was filtered to remove insoluble matters, and the residues obtained after concentration under reduced pressure were purified by high performance liquid chromatography to obtain the title compound (19 mg, 50%).

[1447] .sup.1H-NMR (400 MHz, CD.sub.3OD) : 8.41 (1H, d, 7.9 Hz), 8.27 (1H, d, 8.5 Hz), 7.87 (1 s), 7.81 (1H, s), 7.56 (1H, d, 8.5 Hz), 7.49 (1H, d, 7.9 Hz), 3.71 (4H, t, 4.6 Hz), 3.68 (2H, s), 2.51 (4H, t, 4.6 Hz), 1.82 (6H, s)

[1448] LCMS: m/z 386 [M+H].sup.+

[1449] HPLC retention time: 2.41 min (analysis condition W)

Example 164

Compound B3-33

6,6-Dimethyl-8-(4-methyl-piperazin-1-yl methyl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1450] ##STR00179##

[1451] Under the same conditions as the method for synthesizing Compound B3-32, the title compound was prepared from Compound B2-29 and 1-methylpiperazine.

[1452] .sup.1H-NMR (400 MHz, CD.sub.3OD) : 8.41 (1H, d, 7.9 Hz), 8.26 (1H, d, 7.9 Hz), 7.88 (1 s), 7.81 (1H, s), 7.56 (1H, d, 7.9 Hz), 7.48 (1H, d, 7.9 Hz), 3.70 (2H, s), 2.42-2.78 (8H, m), 2.31 (3H, s), 1.82 (6H, s)

[1453] LCMS: m/z 399 [M+H].sup.+

[1454] HPLC retention time: 2.30 min (analysis condition W)

Example 165

Compound B3-34

8-[4-(1,1-Dioxide-4-thiomorpholinyl)methyl]-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1455] ##STR00180##

[1456] Under the same conditions as the method for synthesizing Compound B3-32, the title compound was prepared from Compound B2-29 and thiomorpholine 1,1-dioxide.

[1457] LCMS: m/z 434 [M+H].sup.+

[1458] HPLC retention time: 2.75 min (analysis condition W)

Example 166

Compound B3-35

8-(4-Methanesulfonyl-piperazin-1-yl methyl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1459] ##STR00181##

[1460] Under the same conditions as the method for synthesizing Compound B3-32, the title compound was prepared from Compound B2-29 and 1-methanesulfonylpiperazine.

[1461] .sup.1H-NMR (400 MHz, CD.sub.3OD) : 8.41 (1H, d, 8.5 Hz), 8.28 (1H, d, 7.9 Hz), 7.87 (1 s), 7.80 (1H, s), 7.56 (1H, d, 8.5 Hz), 7.50 (1H, d, 7.9 Hz), 3.73 (2H, s), 3.24-3.28 (4H, m), 2.85 (3H, s), 2.59-2.65 (4H, m), 1.82 (6H, s)

[1462] LCMS: m/z 463 [M+H].sup.+

[1463] HPLC retention time: 2.47 min (analysis condition W)

Example 167

Compound B3-36

4-(3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl methyl)-piperazine-1-sulfonic Acid Dimethylamide

[1464] ##STR00182##

[1465] Under the same conditions as the method for synthesizing Compound B3-32, the title compound was prepared from Compound B2-29 and piperazine-1-sulfonic acid dimethylamide.

[1466] .sup.1H-NMR (400 MHz, DMSO-d.sub.6) : 12.79 (1H, s), 8.32 (1H, d, 7.9 Hz), 8.18 (1H, d, 7.9 Hz), 8.00 (1 s), 7.77 (1H, s), 7.60 (1H, d, 7.9 Hz), 7.46 (1H, d, 7.9 Hz), 3.67 (2H, s), 3.18-3.23 (4H, m), 2.76 (6H, s), 2.45-2.50 (4H, m), 1.77 (6H, s)

[1467] LCMS: m/z 492 [M+H].sup.+

[1468] HPLC retention time: 2.58 min (analysis condition W)

Example 168

Compound B3-37

6,6-Dimethyl-11-oxo-8-[(2,2,2-trifluoro-ethylamino)-methyl]-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1469] ##STR00183##

[1470] Under the same conditions as the method for synthesizing Compound B3-32, the title compound was prepared from Compound B2-29 and 2,2,2-trifluoroethylamine.

[1471] LCMS: m/z 398 [M+H].sup.+

[1472] HPLC retention time: 2.73 min (analysis condition W)

Example 169

Compound B3-38

8-Hydroxymethyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1473] ##STR00184##

[1474] The by-product obtained from the synthesis of Compound B3-37 was purified by high performance liquid chromatography to obtain the target compound.

[1475] LCMS: m/z 317 [M+H].sup.+

[1476] HPLC retention time: 2.91 min (analysis condition W)

Example 170

Compound B4-1

8-(1-Cyclobutyl-piperidin-4-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1477] ##STR00185##

[1478] Under the same conditions as the method for synthesizing Compound B3-32, the title compound was prepared from Compound B3-13-2 and cyclobutanone.

[1479] .sup.1H-NMR (400 MHz, DMSO-d.sub.6) : 12.73 (1H, s), 8.28-8.33 (1H, m), 8.09-8.14 (1H, m), 7.99 (1H, s), 7.72 (1H, s), 7.56-7.62 (1H, m), 7.34-7.41 (1H, m), 3.52-3.64 (2H, m), 2.85-2.95 (2H, m), 2.56-2.75 (2H, m), 1.91-2.04 (2H, m), 1.56-1.84 (14H, m)

[1480] LCMS: m/z 424 [M+H].sup.+

[1481] HPLC retention time: 1.87 min (analysis condition U)

Example 171

Compound B4-2

8-(1-Methanesulfonyl-piperidin-4-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1482] ##STR00186##

[1483] Under the same conditions as the method for synthesizing Compound A9-1, the title compound was prepared from Compound B3-13-2 and mesyl chloride.

[1484] .sup.1H-NMR (270 MHz, DMSO-d.sub.6) : 12.77 (1H, s), 8.31 (1H, d, 8.6 Hz), 8.15 (1H, d, 8.2 Hz), 8.00 (1H, s), 7.77 (1H, s), 7.59 (1H, d, 7.3 Hz), 7.42 (1H, d, 8.6 Hz), 3.74-3.70 (1H, m), 2.93 (3H, s), 2.86-2.77 (4H, m), 1.93-1.87 (4H, m), 1.77 (6.0H, s)

[1485] LCMS: m/z 448 [M+H].sup.+

[1486] HPLC retention time: 2.37 min (analysis condition S)

Example 172

Compound B4-3-1

Tert-butyl4-(3-cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl)piperidin-1-yl sulfonylcarbamic Acid

[1487] ##STR00187##

[1488] Under the same conditions as the method for synthesizing Compound A9-1, the title compound was prepared from Compound B3-13-2 and N-(tert-butoxycarbonyl)-N-[4-(dimethylazaniumylidene)-1,4-dihydropyridine-1-yl-sulfonyl] azanide.

[1489] LCMS: m/z 549 [M+H].sup.+

[1490] HPLC retention time: 2.72 min (analysis condition S)

Example 173

Compound B4-3-2

4-(3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl)-piperidine-1-sulfonic Acid Amide

[1491] ##STR00188##

[1492] Under the same conditions as the method for synthesizing Compound A8-1, the title compound was prepared from Compound B4-3-1.

[1493] .sup.1H-NMR (400 MHz, DMSO-d.sub.6) : 12.78 (1H, s), 8.29 (1H, d, 7.9 Hz), 8.14 (1H, d, 8.5 Hz), 7.97 (1H, s), 7.76 (1H, s), 7.55 (1H, d, 8.5 Hz), 7.41 (1H, d, 7.9 Hz), 6.79 (2H, s), 3.63 (2H, d, 12.2 Hz), 2.80-2.73 (1H, m), 2.70-2.64 (2H, m), 1.96-1.93 (2H, m), 1.87-1.81 (2H, m), 1.77 (6H, s)

[1494] LCMS: m/z 449 [M+H].sup.+

[1495] HPLC retention time: 2.03 min (analysis condition S)

Example 174

Compound B4-4

4-(3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl)-piperidine-1-sulfonic Acid Methylamide

[1496] ##STR00189##

[1497] Under the same conditions as the method for synthesizing Compound A9-1, the title compound was prepared from Compound B3-13-2 and 2-oxooxazolidine-3-sulfonic acid methylamide.

[1498] LCMS: m/z 463 [M+H].sup.+

[1499] HPLC retention time: 2.40 min (analysis condition S)

Example 175

Compound B4-5

4-(3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl)-piperidine-1-sulfonic acid dimethylamide

[1500] ##STR00190##

[1501] Under the same conditions as the method for synthesizing Compound A9-1, the title compound was prepared from Compound B3-13-2 and dimethylsulfamoyl chloride.

[1502] LCMS: m/z 477 [M+H].sup.+

[1503] HPLC retention time: 2.65 min (analysis condition S)

Example 176

Compound B4-6

6,6-Dimethyl-8-(1-methyl-piperidin-4-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1504] ##STR00191##

[1505] Under the same conditions as the method for synthesizing Compound A9-1, the title compound was prepared from Compound B3-13-2 and iodomethane.

[1506] LCMS: m/z 384 [M+H].sup.+

[1507] HPLC retention time: 1.50 min (analysis condition S)

Example 177

Compound B4-7

8-(1-Isopropyl-piperidin-4-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1508] ##STR00192##

[1509] Under the same conditions as the method for synthesizing Compound B3-32, the title compound was prepared from Compound B3-13-2 and acetone.

[1510] .sup.1H-NMR (400 MHz, DMSO-d.sub.6) : 12.77 (1H, s), 8.32 (1H, d, 7.9 Hz), 8.13 (1H, d, 7.9 Hz), 8.01 (1H, s), 7.73 (1H, s), 7.61 (1H, d, 9.1 Hz), 7.39 (1H, d, 9.8 Hz), 2.93 (2H, d, 11.0 Hz), 2.77-2.71 (1H, m), 2.67-2.62 (1H, m), 2.25 (2H, t, 10.1 Hz), 1.80-1.73 (10H, m), 1.02 (6H, d, 6.7 Hz)

[1511] LCMS: m/z 412 [M+H].sup.+

[1512] HPLC retention time: 1.60 min (analysis condition S)

Example 178

Compound B4-8

6,6-Dimethyl-8-(1-oxetan-3-yl-piperidin-4-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1513] ##STR00193##

[1514] Under the same conditions as the method for synthesizing Compound B3-32, the title compound was prepared from Compound B3-13-2 and oxetan-3-one.

[1515] .sup.1H-NMR (400 MHz, DMSO-d.sub.6) : 12.74 (1H, s), 8.32 (1H, d, 7.9 Hz), 8.13 (1H, d, 7.9 Hz), 8.00 (1H, s), 7.74 (1H, s), 7.61 (1H, d, 9.8 Hz), 7.40 (1H, d, 7.9 Hz), 4.56 (2H, t, 6.7 Hz), 4.46 (2H, t, 6.1 Hz), 3.46-3.39 (1H, m), 2.85-2.82 (2H, m), 2.71-2.64 (1H, m), 1.92-1.86 (2H, m), 1.82-1.79 (4H, m), 1.77 (6H, s)

[1516] LCMS: m/z 426 [M+H].sup.+

[1517] HPLC retention time: 1.53 min (analysis condition S)

[1518] Sulfuric acid salt of Compound B4-8

[1519] 6,6-Dimethyl-8-(1-oxetan-3-yl-piperidin-4-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile was dissolved at 80 C. in a mixture of 5 volumes of DMA and 1.4 volumes of 2 N sulfuric acid. After cooling to room temperature, 15 volumes of acetone were added dropwise, and the precipitated solids were filtered and dried to obtain sulfuric acid salt of 6,6-dimethyl-8-(1-oxetan-3-yl-piperidin-4-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile.

[1520] .sup.1H-NMR (400 MHz, DMSO-d.sub.6) : 12.81 (1H, s), 10.26 (1H, br. s), 8.33 (1H, d, 8.3 Hz), 8.21 (1H, d, 8.3 Hz), 8.04 (1H, s), 7.75 (1H, s), 7.63 (1H, d, 8.3 Hz), 7.41 (1H, d, 8.3 Hz), 4.85-4.70 (4H, m), 4.50-4.40 (1H, br. s), 3.60-3.00 (6H, br. m), 2.20-2.10 (2H, m), 2.05-1.90 (2H, m), 1.79 (6H, s)

[1521] LCMS: m/z 426 [M+H].sup.+

Example 179

Compound B4-9

4-(3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl)-piperidine-1-carboxylic Acid Ethylamide

[1522] ##STR00194##

[1523] Under the same conditions as the method for synthesizing Compound A9-1, the title compound was prepared from Compound B-3-13-2 and ethylisocyanate.

[1524] LCMS: m/z 441 [M+H].sup.+

[1525] HPLC retention time: 2.20 min (analysis condition S)

Example 180

Compound B4-10

8-[1-(Imidazole-1-sulfonyl)-piperidin-4-yl]-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1526] ##STR00195##

[1527] According to the method disclosed in Journal of Organic Chemistry, 2003, page 115, 6,6-dimethyl-11-oxo-8-piperidin-4-yl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (Compound B3-13-2, 10 mg, 0.027 mmol) was reacted with 3-(imidazole-1-sulfonyl)-1-methyl-3H-imidazol-1-ium (19 mg, 2 eq.). After removing the solvent, the residues were purified by liquid chromatography to obtain the title compound (3 mg).

[1528] LCMS: m/z 500 [M+H].sup.+

[1529] HPLC retention time: 2.80 min (analysis condition C)

Example 181

Compound CC1

3-Methoxy-5,5-dimethyl-6-oxo-5,6,7,8-tetrahydro-naphthalen-2-sulfonyl chloride

[1530] ##STR00196##

[1531] To the dichloromethane (2 ml) solution of 7-methoxy-1,1-dimethyl-3,4-dihydro-1H-naphthalen-2-one (Compound A2, 200 mg, 0.980 mmol), chlorosulfonic acid (110 l, 1.70 eq.) was added and the mixture was stirred at room temperature for 2 hr. To the reaction solution, oxalyl chloride (297 l, 3.0 eq.) and N,N-dimethyl formamide (45 l, 0.6 eq.) were added in three divided portions, and the mixture was stirred at room temperature for 30 min. The reaction solution was concentrated under reduced pressure to obtain the title compound (295 mg). Since the title compound is unstable, its structure was identified in the next step.

Example 182

Compound CC2-1

7-Methoxy-1,1-dimethyl-6-(pyrrolidine-1-sulfonyl)-3,4-dihydro-1H-naphthalen-2-one

[1532] ##STR00197##

[1533] The THF (4 ml) solution of 3-methoxy-5,5-dimethyl-6-oxo-5,6,7,8-tetrahydro-naphthalen-2-sulfonyl chloride (Compound CC1, 295 mg, 0.974 mmol) was cooled to 0 C., and the tetrafuran (1 ml) solution combining pyrrolidine (121 l, 1.5 eq.) and triethylamine (272 l, 2 eq.) was added dropwise thereto over 2 min. The mixture was stirred at 0 C. until Compound CC-1 disappears. The reaction solution was added with distilled water and extracted with ethyl acetate. The organic layer was washed with 10% aqueous solution of disodium ethylenediamine tetraacetic acid. The organic layer was washed with brine and dried over sodium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain the title compound (246 mg, 75%).

[1534] .sup.1H-NMR (400 MHz, CDCl.sub.3) : 7.76 (1H, s), 6.93 (1H, s), 3.95 (3H, s), 3.37-3.46 (4H, m), 3.09 (0.0H, t, J=6.9 Hz), 2.69 (0.0H, t, J=6.9 Hz), 1.82-1.91 (4H, m), 1.47 (6H, s)

[1535] LCMS: m/z 338 [M+H].sup.+

[1536] HPLC retention time: 3.21 min (analysis condition W)

Example 183

Compound CC2-2

7-Methoxy-1,1-dimethyl-6-(4-methyl-piperazine-1-sulfonyl)-3,4-dihydro-1H-naphthalen-2-one

[1537] ##STR00198##

[1538] Under the same conditions as the method for synthesizing Compound CC2-1, the title compound was prepared from Compound CC1 and N-methylpiperazine.

[1539] LCMS: m/z 367 [M+H].sup.+

[1540] HPLC retention time: 2.22 min (analysis condition Y)

Example 184

Compound CC3-1

8-Methoxy-6,6-dimethyl-9-(pyrrolidine-1-sulfonyl)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1541] ##STR00199##

[1542] Under the same conditions as the method for synthesizing Compound E2-1, the title compound was prepared from Compound CC2-1.

[1543] LCMS: m/z 436 [M+H].sup.+

[1544] HPLC retention time: 3.76 min (analysis condition W)

Example 185

Compound CC3-2

3-Bromo-8-methoxy-6,6-dimethyl-9-(4-methyl-piperazine-1-sulfonyl)-6,11-dihydro-5H-benzo[b]carbazole

[1545] ##STR00200##

[1546] Under the same conditions as the method for synthesizing Compound A3-1, the title compound was prepared from Compound CC2-2.

[1547] LCMS: m/z 519 [M+H].sup.+

[1548] HPLC retention time: 2.99 min (analysis condition Y)

Example 186

Compound CC4-1

8-Methoxy-6,6-dimethyl-11-oxo-9-(pyrrolidine-1-sulfonyl)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1549] ##STR00201##

[1550] Under the same conditions as the method for synthesizing Compound A4, the title compound was prepared from Compound CC3-1.

[1551] .sup.1H-NMR (400 MHz, DMSO-d.sub.6) : 12.86 (1H, s), 8.60 (1H, s), 8.30 (1H, d, J=8.5 Hz), 8.01 (1H, s), 7.60 (1H, s), 7.59 (1H, d, J=8.5 Hz), 4.09 (3H, s), 3.21-3.42 (4H, m), 1.72-1.90 (10H, m)

[1552] LCMS: m/z 450 [M+H].sup.+

[1553] HPLC retention time: 3.40 min (analysis condition W)

Example 187

Compound CC4-2

3-Bromo-8-methoxy-6,6-dimethyl-9-(4-methyl-piperazine-1-sulfonyl)-5,6-dihydro-benzo[b]carbazol-11-one

[1554] ##STR00202##

[1555] Under the same conditions as the method for synthesizing Compound A4, the title compound was prepared from Compound CC3-2.

[1556] LCMS: m/z 532, 534 [M+H].sup.+

[1557] HPLC retention time: 2.18 min (analysis condition U)

Example 188

[1558] Compound CC-4-3

8-Methoxy-6,6-dimethyl-9-(4-methyl-piperazine-1-sulfonyl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1559] ##STR00203##

[1560] Under the same conditions as the method for synthesizing Compound A5-2, the title compound was prepared from Compound CC4-2.

[1561] LCMS: m/z 479 [M+H].sup.+

[1562] HPLC retention time: 1.93 min (analysis condition U)

Example 189

Compound C1-1

Dimethyl-sulfamic acid 3-cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl ester

[1563] ##STR00204##

[1564] 8-Hydroxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (Compound A6, 50 mg, 0.165 mmol) was dissolved in DMF (1.5 mL), added with sodium hydride (13 mg, 2.0 eq.) and dimethylsulfamoyl chloride (0.02 mL, 1.2 eq.), and then stirred at room temperature for 1 hr. Water was added to the reaction solution, which was then extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over sodium sulfate. The drying agent was removed by filtration and the residues were concentrated under reduced pressure to obtain the target compound (yellowish white powder, 62 mg, 92%).

[1565] .sup.1H-NMR (270 MHz, DMSO-d.sub.6) : 12.87 (1H, s), 8.40-8.30 (2H, m), 8.05 (1H, s), 7.82 (1H, d, J=1.8 Hz), 7.64 (1H, d, J=7.9 Hz), 7.50 (1H, dd, J=8.5, 2.4 Hz), 2.96 (6H, s), 1.81 (6H, s)

[1566] LCMS: m/z 410 [M+H].sup.+

[1567] HPLC retention time: 2.38 min (analysis condition S)

Example 190

Compound C1-2

Morpholine-4-sulfonic acid 3-cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl Ester

[1568] ##STR00205##

[1569] According to the same method as the method for synthesizing Compound A8-17, the title compound was prepared as a crude product from Compound A6 and Compound A8-18-0.

Example 191

Compound C1-4

4-Methyl-piperazine-1-sulfonic acid 3-cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl Ester

[1570] ##STR00206##

[1571] According to the same method as the method for synthesizing Compound A8-17, the title compound was prepared as a crude product from Compound A6 and Compound A8-19-0.

Example 192

Compound C2-1

3-Cyano-8-hydroxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-9-sulfonic Acid Dimethylamide

[1572] ##STR00207##

[1573] To dimethyl-sulfamic acid 3-cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl ester (Compound C1-1, 250 mg, 0.610 mmol), aluminum chloride (1.0 M, nitromethane solution (1.8 mL, 3.0 eq.)) was added and the mixture was stirred at 160 C. for 10 min under irradiation with microwave. Water was added to the reaction solution, which was then extracted with dichloromethane. The organic layer was washed with saturated brine and dried over sodium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (dichloromethane/methanol) to obtain the target compound (yellowish white powder, 99 mg, 40%).

[1574] .sup.1H-NMR (270 MHz, DMSO-d.sub.6) : 12.78 (1H, s), 11.72 (1H, s), 8.50 (1H, s), 8.32 (1H, d, J=8.5 Hz), 8.02 (1H, s), 7.62 (1H, d, J=7.9 Hz), 7.25 (1H, s), 2.80 (6H, s), 1.75 (6H, s).

[1575] LCMS: m/z 410 [M+H].sup.+

[1576] HPLC retention time: 2.00 min (analysis condition S)

Example 193

Compound C2-2

8-Hydroxy-6,6-dimethyl-11-oxo-9-(pyrrolidine-1-sulfonyl)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1577] ##STR00208##

[1578] Under the same conditions as the method for synthesizing Compound E3-2, the title compound was prepared from Compound CC4-1.

[1579] LCMS: m/z 436 [M+H].sup.+

[1580] HPLC retention time: 3.32 min (analysis condition W)

Example 194

Compound C2-3

8-Hydroxy-6,6-dimethyl-9-(morpholine-4-sulfonyl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1581] ##STR00209##

[1582] Under the same conditions as the method for synthesizing Compound C2-1, the title compound was prepared from Compound C1-2.

[1583] LCMS: m/z 452 [M+H].sup.+

[1584] HPLC retention time: 1.89 min (analysis condition S)

Example 195

Compound C2-4

8-Hydroxy-6,6-dimethyl-9-(4-methyl-piperazine-1-sulfonyl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1585] ##STR00210##

[1586] Under the same conditions as the method for synthesizing Compound E3-2, the title compound was prepared from Compound CC4-3.

[1587] LCMS: m/z 465 [M+H].sup.+

[1588] HPLC retention time: 1.87 min (analysis condition U)

Example 196

Compound C3-1

Trifluoro-methanesulfonic Acid 3-cyano-9-dimethylsulfamoyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl Ester

[1589] ##STR00211##

[1590] Under the same conditions as the method for synthesizing Compound B1, the title compound was prepared from Compound C2-1.

[1591] .sup.1H-NMR (270 MHz, DMSO-d.sub.6) : 13.05 (1H, s), 8.67 (1H, s), 8.32 (1H, d, J=8.2 Hz), 8.06 (2H, m), 7.67 (1H, dd, J=7.9, 1.3 Hz), 2.79 (6H, s), 1.84 (6H, s).

[1592] LCMS: m/z 542 [M+H].sup.+

[1593] HPLC retention time: 2.67 min (analysis condition S)

Example 197

Compound C3-2

Trifluoro-methanesulfonic Acid 3-cyano-6,6-dimethyl-11-oxo-9-(pyrrolidine-1-sulfonyl)-6,11-dihydro-5H-benzo[b]carbazol-8-yl Ester

[1594] ##STR00212##

[1595] Under the same conditions as the method for synthesizing Compound B1, the title compound was prepared from Compound C2-2.

[1596] LCMS: m/z 568 [M+H].sup.+

[1597] HPLC retention time: 4.00 min (analysis condition W)

Example 198

Compound C4-1

3-Cyano-8-(2-methoxy-ethoxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-9-sulfonic Acid Dimethylamide

[1598] ##STR00213##

[1599] Under the same conditions as the method for synthesizing Compound A7-17, the title compound was prepared from Compound C2-1 and 1-bromo-2-methoxy-ethane.

[1600] .sup.1H-NMR (300 MHz, DMSO-d.sub.6) ppm; 12.8 (s, 1H), 8.58 (s, 1H), 8.31 (d, 1H, J=8.4 Hz), 8.03 (s, 1H), 7.62 (m, 2H), 4.47 (m, 2H), 3.75 (m, 2H), 3.32 (s, 3H), 2.27 (s, 6H), 1.83 (s, 6H)

[1601] LCMS: m/z 468 [M+H].sup.+

[1602] HPLC retention time: 2.68 min (analysis condition U)

Example 199

Compound C4-2

3-Cyano-8-(2-diethylamino-ethoxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-9-sulfonic Acid Dimethylamide

[1603] ##STR00214##

[1604] Under the same conditions as the method for synthesizing Compound A7-17, the title compound was prepared from Compound C2-1.

[1605] .sup.1H-NMR (270 MHz, DMSO-d.sub.6) : 8.57 (1H, s), 8.29 (1H, d, J=8.4 Hz), 8.02 (1H, s), 7.70-7.60 (2H, m), 4.37 (2H, t, J=6.3 Hz), 2.84 (2H, m), 2.80 (6H, s), 2.64-2.53 (4H, m), 1.83 (6H, s), 0.98 (6H, t, J=7.1 Hz).

[1606] LCMS: m/z 509 [M+H].sup.+

[1607] HPLC retention time: 1.55 min (analysis condition S)

Example 200

Compound C4-3

3-Cyano-8-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-9-sulfonic Acid Dimethylamide

[1608] ##STR00215##

[1609] Under the same conditions as the method for synthesizing Compound A7-17, the title compound was prepared from Compound C2-1 and iodomethane.

[1610] LCMS: m/z 424 [M+H].sup.+

[1611] HPLC retention time: 2.17 min (analysis condition S)

Example 201

Compound C4-4

3-Cyano-6,6-dimethyl-11-oxo-8-(piperidin-4-yl oxy)-6,11-dihydro-5H-benzo[b]carbazole-9-sulfonic acid dimethylamide

[1612] ##STR00216##

[1613] Under the same conditions as the method for synthesizing Compound A7-1 and Compound A8-1, the title compound was prepared from Compound C2-1 and 4-hydroxy-piperidine-1-carboxylic acid tert-butyl ester.

[1614] LCMS: m/z 493 [M+H].sup.+

[1615] HPLC retention time: 1.49 min (analysis condition S)

Example 202

Compound C4-5

3-Cyano-6,6-dimethyl-8-(2-morpholin-4-yl-ethoxy)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-9-sulfonic Acid Dimethylamide

[1616] ##STR00217##

[1617] Under the same conditions as the method for synthesizing Compound A7-1, the title compound was prepared from Compound C2-1 and 2-morpholin-4-yl-ethanol.

[1618] LCMS: m/z 523 [M+H].sup.+

[1619] HPLC retention time: 1.64 min (analysis condition S)

Example 203

Compound C4-6

3-Cyano-8-[2-(1,1-dioxo-thiomorpholin-4-yl)-ethoxy]-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-9-sulfonic Acid Dimethylamide

[1620] ##STR00218##

[1621] Under the same conditions as the method for synthesizing Compound A7-1, the title compound was prepared from Compound C2-1 and 2-(1,1-dioxothiomorpholino)ethanol.

[1622] LCMS: m/z 571 [M+H].sup.+

[1623] HPLC retention time: 1.75 min (analysis condition S)

Example 204

Compound C4-7

3-Cyano-8-(1-ethyl-piperidin-4-yl oxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-9-sulfonic Acid Dimethylamide

[1624] ##STR00219##

[1625] Under the same conditions as the method for synthesizing Compound A7-1, the title compound was prepared from Compound C2-1 and 1-ethyl-piperidin-4-ol.

[1626] LCMS: m/z 521 [M+H].sup.+

[1627] HPLC retention time: 1.52 min (analysis condition S)

Example 205

Compound C4-8

3-Cyano-8-(4-isopropyl-piperazin-1-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-9-sulfonic Acid Dimethylamide

[1628] ##STR00220##

[1629] Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound C3-1.

[1630] .sup.1H-NMR (270 MHz, DMSO-d.sub.6) : 8.61 (1H, s), 8.30 (1H, d, J=8.1 Hz), 8. 04 (1H, s), 7.87 (1H, s), 7.62 (1H, dd, J=8.2, 1.8 Hz), 3.17-3.06 (2H, m), 2.75-2.70 (6H, s), 2.67-2.58 (2H, m), 1.81 (6H, s), 1.02 (6H, d, J=6.4 Hz).

[1631] LCMS: m/z 520 [M+H].sup.+

[1632] HPLC retention time: 1.52 min (analysis condition S)

Example 206

Compound C4-9

3-Cyano-8-[4-(2-hydroxy-ethyl)-piperazin-1-yl]-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-9-sulfonic Acid Dimethylamide

[1633] ##STR00221##

[1634] Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound C3-1 and 2-piperazin-1-yl-ethanol.

[1635] LCMS: m/z 522 [M+H].sup.+

[1636] HPLC retention time: 1.40 min (analysis condition S)

Example 207

Compound C4-10

3-Cyano-6,6-dimethyl-8-morpholin-4-yl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-9-sulfonic Acid Dimethylamide

[1637] ##STR00222##

[1638] Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound C3-1 and morpholine.

[1639] LCMS: m/z 479 [M+H].sup.+

[1640] HPLC retention time: 2.22 min (analysis condition S)

Example 208

Compound C4-11

4-(3-Cyano-9-dimethylsulfamoyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl)-piperazine-1-carboxylic Acid Tert-Butyl Ester

[1641] ##STR00223##

[1642] Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound C3-1 and piperazine-1-carboxylic acid tert-butyl ester.

[1643] LCMS: m/z 578 [M+H].sup.+

[1644] HPLC retention time: 2.72 min (analysis condition S)

Example 209

Compound C4-12

3-Cyano-6,6-dimethyl-11-oxo-8-piperazin-1-yl-6,11-dihydro-5H-benzo[b]carbazole-9-sulfonic Acid Dimethylamide

[1645] ##STR00224##

[1646] Under the same conditions as the method for synthesizing Compound A8-1, the title compound was prepared from C.sub.4-11.

[1647] .sup.1H-NMR (270 MHz, CD.sub.3OD) : 8.78 (1H, s), 8.39 (1H, dd, J=8.2, 0.7 Hz), 7.88 (1H, m), 7.75 (1.1H, s), 7.55 (1H, dd, J=8.2, 1.5 Hz), 3.15 (4H, m), 3.04 (4H, m), 2.82 (s, 6H), 1.85 (6H, s)

[1648] LCMS: m/z 478 [M+H].sup.+

[1649] HPLC retention time: 1.43 min (analysis condition S)

Example 210

Compound C4-13

6,6-Dimethyl-11-oxo-9-(pyrrolidine-1-sulfonyl)-8-(4-pyrrolidin-1-yl-piperidin-1-yl)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1650] ##STR00225##

[1651] Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound C3-2 and 4-(1-pyrrolidyl)-piperidine.

[1652] .sup.1H-NMR (400 MHz, DMSO-d.sub.6) : 12.83 (1H, s), 8.64 (1H, s), 8.32 (1H, d, 8.2 Hz), 8.03 (1H, s), 7.80 (1H, s), 7.63 (1H, d, 8.2 Hz), 2.87-2.94 (4H, m), 1.94-1.99 (4H, m), 1.80 (6H, s), 1.58-1.76 (10H, m)

[1653] LCMS: m/z 572 [M+H].sup.+

[1654] HPLC retention time: 2.81 min (analysis condition W)

Example 211

Compound C4-14

8-(2-Diethylamino-ethoxy)-6,6-dimethyl-9-(morpholine-4-sulfonyl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1655] ##STR00226##

[1656] Under the same conditions as the method for synthesizing Compound A7-17, the title compound was prepared from Compound C2-3.

[1657] LCMS: m/z 551 [M+H].sup.+

[1658] HPLC retention time: 1.46 min (analysis condition S)

Example 212

Compound C4-15

6,6-Dimethyl-9-(morpholine-4-sulfonyl)-11-oxo-8-(tetrahydro-pyran-4-yl oxy)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1659] ##STR00227##

[1660] Under the same conditions as the method for synthesizing Compound A7-1, the title compound was prepared from Compound C2-3 and tetrahydropyran-4-ol.

[1661] LCMS: m/z 536 [M+H].sup.+

[1662] HPLC retention time: 2.05 min (analysis condition S)

Example 213

Compound C4-16

6,6-Dimethyl-9-(4-methyl-piperazine-1-sulfonyl)-11-oxo-8-(tetrahydro-pyran-4-yl oxy)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1663] ##STR00228##

[1664] Under the same conditions as the method for synthesizing Compound A7-1, the title compound was prepared from Compound C2-4 and tetrahydropyran-4-ol.

[1665] LCMS: m/z 549 [M+H].sup.+

[1666] HPLC retention time: 2.03 min (analysis condition U)

Example 214

Compound C4-17

8-(2-Diethylamino-ethoxy)-6,6-dimethyl-9-(4-methyl-piperazine-1-sulfonyl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1667] ##STR00229##

[1668] Under the same conditions as the method for synthesizing Compound A7-1, the target compound was prepared from Compound C2-3.

[1669] LCMS: m/z 564 [M+H].sup.+

[1670] HPLC retention time: 1.20 min (analysis condition S)

Example 215

Compound C5

3-Cyano-8-methoxy-5,6,6-trimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-9-sulfonic Acid Dimethylamide

[1671] ##STR00230##

[1672] The title compound was obtained as a by-product of the synthesis of Compound C4-3.

[1673] LCMS: m/z 438 [M+H].sup.+

[1674] HPLC retention time: 2.29 min (analysis condition S)

Example 216

Compound D0-1-1

7-Methoxy-1,1-dimethyl-6-nitro-3,4-dihydro-1H-naphthalen-2-one

[1675] ##STR00231##

[1676] Tetrabutylammonium nitrate (2.47 g, 1.07 eq.) was dissolved in dichloromethane, and added with trifluoromethanesulfonic anhydride (1.33 ml, 1.07 eq.) at 0 C. The mixture was stirred for 1 hr, added with DCM solution of 7-methoxy-1,1-dimethyl-3,4-dihydro-1H-naphthalen-2-one (Compound A2, 1.55 g, 7.59 mmol), and then stirred at 0 C. for 2 hr and 30 min. The reaction solution was added to saturated aqueous solution of sodium hydrogen carbonate and then extracted with ethyl acetate. The organic layer was washed with brine and dried over sodium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain the title compound (pale yellow solid, 1.144 g, 60%).

[1677] .sup.1H-NMR (270 MHz, DMSO-d.sub.6) : 7.79 (1H, s), 7.28 (1H, s), 3.95 (3H, s), 3.06 (2H, t, J=6.9 Hz), 2.64 (2H, t, J=6.9 Hz), 1.41 (6H, s).

[1678] HPLC retention time: 2.03 min (analysis condition S)

Example 217

Compound D0-1-2

7-Methoxy-1,1-dimethyl-8-nitro-3,4-dihydro-1H-naphthalen-2-one

[1679] ##STR00232##

[1680] The title compound was obtained as a by-product of the synthesis of Compound D0-1-1.

[1681] .sup.1H-NMR (270 MHz, DMSO-d.sub.6) : 7.44 (1H, d, J=8.6 Hz), 7.23 (1H, d, J=8.6 Hz), 3.84 (3H, s), 3.07 (2H, t, J=6.9 Hz), 2.65 (2H, t, J=6.9 Hz), 1.35 (6H, s)

[1682] HPLC retention time: 2.15 min (analysis condition S)

Example 218

Compound D0-2-1

3-Bromo-8-methoxy-6,6-dimethyl-9-nitro-6,11-dihydro-5H-benzo[b]carbazole

[1683] ##STR00233##

[1684] Under the same conditions as the method for synthesizing Compound A3-1, the title compound was prepared from Compound D0-1-1.

[1685] LCMS: m/z 401,403 [M+H].sup.+

[1686] HPLC retention time: 3.07 min (analysis condition S)

Example 219

Compound D0-2-2

3-Bromo-8-methoxy-6,6-dimethyl-7-nitro-6,11-dihydro-5H-benzo[b]carbazole

[1687] ##STR00234##

[1688] Under the same conditions as the method for synthesizing Compound A3-1, the title compound was prepared from Compound D0-1-2.

[1689] LCMS: m/z 401, 403 [M+H].sup.+

[1690] HPLC retention time: 3.10 min (analysis condition S)

Example 220

Compound D0-3-1

3-Bromo-8-methoxy-6,6-dimethyl-9-nitro-5,6-dihydro-benzo[b]carbazol-11-one

[1691] ##STR00235##

[1692] Under the same conditions as the method for synthesizing Compound A4, the title compound was prepared from Compound D0-2-1.

[1693] LCMS: m/z 415, 417 [M+H].sup.+

[1694] HPLC retention time: 3.07 min (analysis condition S)

Example 221

Compound D0-3-2

3-Bromo-8-methoxy-6,6-dimethyl-7-nitro-5,6-dihydro-benzo[b]carbazol-11-one

[1695] ##STR00236##

[1696] Under the same conditions as the method for synthesizing Compound A4, the title compound was prepared from Compound D0-2-2.

[1697] LCMS: m/z 415, 417 [M+H].sup.+

[1698] HPLC retention time: 2.72 min (analysis condition S)

Example 222

Compound D0-4-1

8-Methoxy-6,6-dimethyl-9-nitro-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1699] ##STR00237##

[1700] Under the same conditions as the method for synthesizing Compound A5-2, the title compound was prepared from Compound D0-3-1.

[1701] LCMS: m/z 362 [M+H].sup.+

[1702] HPLC retention time: 2.35 min (analysis condition S)

Example 223

Compound D0-4-2

8-Methoxy-6,6-dimethyl-7-nitro-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1703] ##STR00238##

[1704] Under the same conditions as the method for synthesizing Compound A5-2, the title compound was prepared from Compound D0-3-2.

[1705] LCMS: m/z 362 [M+H].sup.+

[1706] HPLC retention time: 2.35 min (analysis condition S)

Example 224

Compound D0-5-1

8-Hydroxy-6,6-dimethyl-9-nitro-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1707] ##STR00239##

[1708] Under the same conditions as the method for synthesizing Compound A6, the title compound was prepared from Compound D0-4-1.

[1709] LCMS: m/z 348 [M+H].sup.+

[1710] HPLC retention time: 2.28 min (analysis condition S)

Example 225

Compound D0-5-2

8-Hydroxy-6,6-dimethyl-7-nitro-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1711] ##STR00240##

[1712] Under the same conditions as the method for synthesizing Compound A6, the title compound was prepared from Compound D0-4-2.

[1713] LCMS: m/z 348 [M+H].sup.+

[1714] HPLC retention time: 2.23 min (analysis condition S)

Example 226

Compound D1

6,6-Dimethyl-8-(1-methyl-piperidin-4-yl oxy)-9-nitro-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1715] ##STR00241##

[1716] Under the same conditions as the method for synthesizing Compound A7-1, the title compound was prepared from Compound D0-5-1 and 1-methylpiperidin-4-ol.

[1717] LCMS: m/z 445 [M+H].sup.+

[1718] HPLC retention time: 1.64 min (analysis condition S)

Example 227

Compound D2

9-Amino-6,6-dimethyl-8-(1-methyl-piperidin-4-yl oxy)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1719] ##STR00242##

[1720] 6,6-Dimethyl-8-(1-methyl-piperidin-4-yl oxy)-9-nitro-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (Compound D1, 83 mg, 0.19 mmol) was dissolved in ethanol, added with aqueous solution of ammonium acetate and aqueous solution of titanium (III) chloride, and then the mixture was stirred at room temperature for 45 min. The reaction solution was added to saturated aqueous solution of sodium hydrogen carbonate and then extracted with ethyl acetate. The organic layer was washed with brine and dried over sodium sulfate. The drying agent was removed by filtration and the residues were concentrated under reduced pressure to obtain the title compound (yellow solid, 60 mg, 78%).

[1721] .sup.1H-NMR (270 MHz, DMSO-d.sub.6) : 12.61 (1H, br. s), 8.28-8.34 (1H, m), 7.94-8.00 (1H, m), 7.57 (1H, dd, J=8.2, 1.4 Hz), 7.46 (1H, s), 7.19 (1H, s), 4.93 (1.8H, s), 4.65 (1.0H, s), 4.06-4.15 (1H, m), 3.34 (5.7H, s), 3.16-3.18 (2H, m), 2.55-2.67 (2H, m), 2.17-2.33 (5H, m), 1.89-2.07 (2H, m), 1.65-1.81 (8H, m)

[1722] LCMS: m/z 415 [M+H].sup.+

[1723] HPLC retention time: 1.12 min (analysis condition S)

Example 228

Compound D3-1

N-[3-Cyano-6,6-dimethyl-8-(1-methyl-piperidin-4-yl oxy)-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-9-yl]-methanesulfonamide

[1724] ##STR00243##

[1725] Under the same conditions as the method for synthesizing Compound A9-1, the title compound was prepared from Compound D2 and methanesulfonyl chloride.

[1726] LCMS: m/z 493 [M+H].sup.+

[1727] HPLC retention time: 1.43 min (analysis condition S)

Example 229

Compound D3-2

3-Cyano-6,6-dimethyl-11-oxo-8-(1-methylpiperidin-4-yl oxy)-6,11-dihydro-5H-benzo[b]carbazole-9-sulfonic Acid Dimethylamide

[1728] ##STR00244##

[1729] Under the same conditions as the method for synthesizing Compound A9-1, the title compound was prepared from Compound D2 and dimethylsulfamoyl chloride.

[1730] .sup.1H-NMR (270 MHz, CD.sub.3OD) : 8.34-8.42 (2. OH, m), 7.85 (1.0H, s), 7.47-7.58 (1.0H, m), 7.32 (1.0H, s), 4.73-4.89 (1H, m), 2.75-2.91 (8H, m), 2.38-2.52 (2H, m), 2.34 (3H, s), 2.06-2.21 (2H, m), 1.87-2.05 (2H, m), 1.80 (6H, s).

[1731] LCMS: m/z 522 [M+H].sup.+

[1732] HPLC retention time: 1.66 min (analysis condition S)

Example 230

Compound D3-3

N-[3-Cyano-6,6-dimethyl-8-(1-methyl-piperidin-4-yl oxy)-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-9-yl]-2-dimethylamino-acetamide

[1733] ##STR00245##

[1734] Under the same conditions as the method for synthesizing Compound A9-10, the title compound was prepared from Compound D2 and N,N-dimethylglycine.

[1735] LCMS: m/z 500 [M+H].sup.+

[1736] HPLC retention time: 1.31 min (analysis condition S)

Example 231

Compound E1

6-Bromo-7-methoxy-1,1-dimethyl-3,4-dihydro-1H-naphthalen-2-one

[1737] ##STR00246##

[1738] 7-Methoxy-1,1-dimethyl-3,4-dihydro-1H-naphthalen-2-one (Compound A2, 2.0 g, 9.791 mmol) was dissolved in CH.sub.3CN (40 mL), added with NBS (1.92 g, 1.1 eq.), and the mixture was stirred at room temperature for 2.5 hr. The reaction solution was added to water (40 mL), and the precipitated solid was filtered to obtain the title compound (white powder, 2.55 g, 92%).

[1739] .sup.1H-NMR (270 MHz, CDCl.sub.3) : 7.36 (1H, s), 6.84 (1H, s), 3.91 (3H, s), 3.02 (2H, t, J=6.8 Hz), 2.66 (2H, t, J=6.8 Hz), 1.42 (6H, s).

[1740] LCMS: m/z 283, 285 [M+H].sup.+

[1741] HPLC retention time: 2.67 min (analysis condition S)

Example 232

Compound E2-1

9-Bromo-8-methoxy-6,6-dimethyl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1742] ##STR00247##

[1743] 6-Bromo-7-methoxy-1,1-dimethyl-3,4-dihydro-1H-naphthalen-2-one (Compound E1, 7.89 g, 27.85 mmol) and 3-hydrazino-benzonitrile (4.45 g, 1.2 eq.) were dissolved in TFA (250 mL), and stirred at 100 C. for 2 hr. TFA was removed under reduced pressure and the residues were added with saturated aqueous solution of NaHCO.sub.3 (500 mL), followed by extraction with ethyl acetate. The organic layer was washed with saturated brine and dried over sodium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were added with ethyl acetate. After stirring at room temperature, the precipitated solid was separated by filtration (Compound E2-2). The filtrate was concentrated under reduced pressure to obtain the title compound as a mixture with E2-2 (yellowish white powder, 2.65 g).

[1744] LCMS: m/z 381, 383 [M+H].sup.+

[1745] HPLC retention time: 3.03 min (analysis condition S)

Example 233

Compound E2-2

9-Bromo-8-methoxy-6,6-dimethyl-6,11-dihydro-5H-benzo[b]carbazole-1-carbonitrile

[1746] ##STR00248##

[1747] The title compound was obtained as a by-product of the synthesis of Compound E2-1.

[1748] .sup.1H-NMR (270 MHz, DMSO-d.sub.6) : 11.70 (1H, s), 7.69 (1H, dd, J=8.1, 0.8 Hz), 7.55 (1H, s), 7.48 (1H, dd, J=7.4, 0.8 Hz), 7.27 (1H, s), 7.22 (1H, dd, J=8.1, 7.4 Hz), 4.23 (2H, s), 3.91 (3H, s), 1.70 (6H, s).

[1749] LCMS: m/z 381, 383 [M+H].sup.+

[1750] HPLC retention time: 2.92 min (analysis condition S)

Example 234

Compound E2-3, Compound E2-4

3,9-Dibromo-8-methoxy-6,6-dimethyl-6,11-dihydro-5H-benzo[b]carbazole 1,9-Dibromo-8-methoxy-6,6-dimethyl-6,11-dihydro-5H-benzo[b]carbazole

[1751] ##STR00249##

[1752] Under the same conditions as the method for synthesizing Compound A4, the title compound was prepared (as a mixture) from Compound E1.

Example 235

Compound E3-1-1

9-Bromo-8-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1753] ##STR00250##

[1754] Under the same conditions as the method for synthesizing Compound A4, the title compound was prepared from Compound E2-1.

[1755] .sup.1H-NMR (270 MHz, DMSO-d.sub.6) : 12.82 (1H, s), 8.30 (2H, s+d), 8.03 (1H, s), 7.61 (1H, dd, J=8.2, 1.4 Hz), 7.49 (1H, s), 4.04 (3H, s), 1.81 (6H, s).

[1756] LCMS: m/z 395, 397 [M+H].sup.+

[1757] HPLC retention time: 2.77 min (analysis condition S)

Example 236

Compound E3-1-2

9-Bromo-8-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-1-carbonitrile

[1758] ##STR00251##

[1759] The title compound was obtained as a by-product of the synthesis of Compound E3-1-1.

[1760] .sup.1H-NMR (270 MHz, DMSO-d.sub.6) : 12.84 (1H, s), 8.31 (1H, s), 7.86 (1H, dd, J=8.2, 0.9 Hz), 7.70 (1H, d, J=7.1 Hz), 7.47 (1H, s), 7.43 (1H, t, J=7.8 Hz), 4.04 (3H, s), 1.81 (6H, s).

[1761] LCMS: m/z 395, 397 [M+H].sup.+

[1762] HPLC retention time: 2.42 min (analysis condition S)

Example 237

Compound E3-1-3

3,9-Dibromo-8-methoxy-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one

[1763] ##STR00252##

[1764] Under the same conditions as the method for synthesizing Compound A4, the title compound was prepared from Compound E2-3 and Compound E2-4 (mixture).

[1765] .sup.1H-NMR (270 MHz, DMSO-d.sub.6) : 12.42 (1H, s), 8.28 (1H, s), 8.09 (1H, d, J=8.2 Hz), 7.68 (1H, d, J=1.6 Hz), 7.47 (1H, s), 7.39 (1H, dd, J=8.3, 1.7 Hz), 4.03 (3H, s), 1.78 (6H, s).

[1766] LCMS: m/z 448, 450, 452 [M+H].sup.+

[1767] HPLC retention time: 2.93 min (analysis condition S)

Example 238

Compound E3-2

9-Bromo-8-hydroxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1768] ##STR00253##

[1769] 9-Bromo-8-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (Compound E3-1-1, 1.0 g, 2.53 mmol) was dissolved in NMP (10 mL), added with NaOMe (683 mg, 5 eq.) and 1-dodecanethiol (3.0 mL, 5 eq.), and stirred at 160 C. for 1 hr. The reaction solution was added to 0.5 N aqueous solution of hydrochloric acid, and then extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over sodium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were added with MeOH, and the solid remaining after dissolution was filtered to obtain the title compound (yellow powder, 1.88 g, 65%).

[1770] .sup.1H-NMR (400 MHz, DMSO-d.sub.6) : 12.77 (1H, s), 11.13 (1H, d, J=2.4 Hz), 8.31 (1H, dd, J=7.9, 2.4 Hz), 8.25 (1H, d, J=3.0 Hz), 8.01 (1H, s), 7.61 (1H, d, J=7.9 Hz), 7.28 (1H, d, J=2.4 Hz), 1.74 (6H, s).

[1771] LCMS: m/z 381, 383 [M+H].sup.+

[1772] HPLC retention time: 2.40 min (analysis condition S)

Example 239

Compound E3-3

9-Bromo-8-isopropoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1773] ##STR00254##

[1774] Under the same conditions as the method for synthesizing Compound A7-17, the title compound was prepared from Compound E3-2 and 2-bromopropane.

[1775] .sup.1H-NMR (270 MHz, DMSO-d.sub.6) : 12.77 (1H, s), 8.29 (2H, s+d), 8.01 (1H, s), 7.60 (1H, d, J=8.1 Hz), 7.50 (1H, s), 5.03 (1H, m), 1.79 (6H, s), 1.36 (6H, d, J=5.9 Hz).

[1776] LCMS: m/z 423, 425 [M+H].sup.+

[1777] HPLC retention time: 2.98 min (analysis condition S)

Example 240

Compound E4-1

8-Methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3,9-dicarbonitrile

[1778] ##STR00255##

[1779] Under the same conditions as the method for synthesizing Compound A5-2, the title compound was prepared from Compound E3-1-1.

[1780] .sup.1H-NMR (270 MHz, DMSO-d.sub.6) : 12.88 (1H, br. s), 8.43 (1H, s), 8.30 (1H, d, J=8.2 Hz), 8.05 (1H, d, J=0.5 Hz), 7.65-7.62 (2H, m), 4.11 (3H, s), 1.84 (6H, s).

[1781] LCMS: m/z 342 [M+H].sup.+

[1782] HPLC retention time: 2.23 min (analysis condition S)

Example 241

Compound E4-2-1

9-(3-Hydroxy-3-methyl-but-1-ynyl)-8-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1783] ##STR00256##

[1784] 9-Bromo-8-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (Compound E3-1-1, 50 mg, 0.13 mmol), bis (acetonitrile)dichloropalladium (II) (1.64 mg, 0.05 eq.), XPhos (9.05 mg, 0.15 eq.), cesium carbonate (185 mg, 4.5 eq.) and 3-methyl-1-butyn-1-ol (18.6 l, 1.5 eq.) were dissolved in acetonitrile and stirred at 85 C. for 2 hr. The reaction solution was added to water, and then extracted with ethyl acetate. The organic layer was washed with brine and dried over sodium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were purified by HPLC to obtain the title compound (brown solid, 21.3 mg, 42%).

[1785] .sup.1H-NMR (270 MHz, DMSO-d.sub.6) : 8.29 (1H, d, J=8.1 Hz), 8.11 (1H, s), 8.00 (1H, s), 7.57 (1H, d, J=8.1 Hz), 7.40 (1H, s), 5.50 (1H, s), 3.95 (3H, s), 2.54 (1H, s), 1.79 (6H, s), 1.49 (6H, s).

[1786] LCMS: m/z 399 [M+H].sup.+

[1787] HPLC retention time: 2.10 min (analysis condition S)

Example 242

Compound E4-2-2

9-Ethynyl-8-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1788] ##STR00257##

[1789] 9-(3-Hydroxy-3-methyl-but-1-ynyl)-8-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (Compound E4-2-1, 21.3 mg, 0.05 mmol) and sodium hydride (3.2 mg, 1.5 eq.) were dissolved in THF, and the mixture was stirred overnight at 50 C. Water was added to the reaction solution and the residues obtained after concentration under reduced pressure were purified by HPLC to obtain the title compound (brown solid, 9.6 mg, 31%).

[1790] .sup.1H-NMR (270 MHz, DMSO-d.sub.6) : 8.26 (1H, d, J=8.2 Hz), 8.16 (1H, s), 7.97 (1H, s), 7.53 (1H, d, J=8.2 Hz), 7.41 (1H, s), 4.32 (1H, s), 4.00 (3H, s), 1.79 (6H, s).

[1791] LCMS: m/z 341 [M+H].sup.+

[1792] HPLC retention time: 2.27 min (analysis condition S)

Example 243

Compound E4-3

8-Methoxy-6,6-dimethyl-11-oxo-9-vinyl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1793] ##STR00258##

[1794] 9-Bromo-8-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (Compound E3-1-1, 50 mg, 0.13 mmol), [1,1-bis (diphenylphosphino)ferrocene]palladium (II) dichloride dichloromethane complex (1:1) (10.3 mg, 0.1 eq.), TEA (53 l, 3 eq.) and potassium vinyltrifluoroborate (51 mg, 3 eq.) were dissolved in n-propanol and the mixture was stirred at 60 C. for 5 days. The reaction solution was added to water and then extracted with ethyl acetate. The organic layer was washed with brine and dried over sodium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain the title compound (brown powder, 25 mg, 19%).

[1795] LCMS: m/z 343 [M+H].sup.+

[1796] HPLC retention time: 2.55 min (analysis condition S)

Example 244

Compound E4-4

9-(2-Diethylamino-ethylsulfanyl)-8-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1797] ##STR00259##

[1798] Under the same conditions as the method for synthesizing Compound B2-17, the title compound was prepared from Compound E3-1-1.

[1799] LCMS: m/z 448 [M+H].sup.+

[1800] HPLC retention time: 2.05 min (analysis condition U)

Example 245

Compound E4-5

9-Isopropylsulfanyl-8-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1801] ##STR00260##

[1802] Under the same conditions as the method for synthesizing Compound B2-17, the title compound was prepared from Compound E3-1-1 and sodium salt of propane-2-thiol.

[1803] LCMS: m/z 391 [M+H].sup.+

[1804] HPLC retention time: 2.98 min (analysis condition U)

Example 246

Compound E4-6

8-Methoxy-6,6-dimethyl-9-(4-methylpiperazin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1805] ##STR00261##

[1806] Under the same conditions as the method for synthesizing Compound B2-10, the title compound was prepared from Compound E3-1-1 and 1-methylpiperazine.

[1807] .sup.1H-NMR (400 MHz, DMSO-d.sub.6) : 8.25 (1H, d, J=7.8 Hz), 7.93 (1H, s), 7.65 (1H, s), 7.50 (1H, d, J=6.8 Hz), 7.25 (1H, s), 3.93 (3H, s), 3.02 (4H, br), 2.22 (3H, s), 1.73 (6H, s).

[1808] LCMS: m/z 415 [M+H].sup.+

[1809] HPLC retention time: 1.80 min (analysis condition U)

Example 247

Compound E4-7-1

4-(3-Cyano-8-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-9-yl)-3,6-dihydro-2H-pyridine-1-carboxylic Acid Tert-Butyl Ester

[1810] ##STR00262##

[1811] To 9-bromo-8-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (Compound E3-1-1, 300 mg, 0.759 mmol), 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (282 mg, 0.911 mmol, 1.2 eq.), Pd(PPh.sub.3).sub.2Cl.sub.2 (26.6 mg, 0.0379 mmol, 0.05 eq.) and sodium carbonate (241 mg, 2.28 mmol, 3.0 eq.), DME (5 ml) and water (1 ml) were added. The mixture was subjected to reduced pressure under ultrasonication treatment, followed by flushing with nitrogen gas. This procedure was repeated five times and then degassed. The mixture was stirred at 80 C. for 80 min under nitrogen atmosphere. Pd(PPh.sub.3).sub.2Cl.sub.2 (26.6 mg, 0.0379 mmol, 0.05 eq.) was added and the mixture was further stirred at 80 C. for 20 min. Then, the mixture was cooled to room temperature, and added with water and ethyl acetate. The insoluble matters were filtered through Celite. The organic layer was dried over sodium sulfate. The drying agent was removed by filtration, followed by concentration under reduced pressure to obtain the title compound as a crude product (gray powder).

[1812] LCMS: m/z 498 [M+H].sup.+

[1813] HPLC retention time: 2.85 min (analysis condition S)

Example 248

Compound E4-7-2

8-Methoxy-6,6-dimethyl-11-oxo-9-(1,2,3,6-tetrahydro-pyridin-4-yl)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1814] ##STR00263##

[1815] Under the same conditions as the method for synthesizing Compound A8-1, the title compound was prepared from Compound B4-4-1.

[1816] LCMS: m/z 368 [M+H].sup.+

[1817] HPLC retention time: 1.27 min (analysis condition S)

Example 249

Compound E4-8-1

4-(3-Cyano-8-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-9-yl)-piperidine-1-carboxylic Acid Tert-Butyl Ester

[1818] ##STR00264##

[1819] Under the same conditions as the method for synthesizing Compound B3-13-1, the title compound was prepared from Compound B4-7-1.

[1820] LCMS: m/z 500 [M+H].sup.+

[1821] HPLC retention time: 4.18 min (analysis condition W)

Example 250

Compound E4-8-2

8-Methoxy-6,6-dimethyl-11-oxo-9-piperidin-4-yl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1822] ##STR00265##

[1823] Under the same conditions as the method for synthesizing Compound A8-1, the title compound was prepared from Compound B4-8-1.

[1824] LCMS: m/z 400 [M+H].sup.+

[1825] HPLC retention time: 1.35 min (analysis condition S)

Example 251

Compound E4-9-1

4-(3-Cyano-8-isopropoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-9-yl)-3,6-dihydro-2H-pyridine-1-carboxylic Acid Tert-Butyl Ester

[1826] ##STR00266##

[1827] Under the same conditions as the method for synthesizing Compound E4-7-1, the title compound was prepared from Compound E3-3.

[1828] LCMS: m/z 526 [M+H].sup.+

[1829] HPLC retention time: 3.13 min (analysis condition S)

Example 252

Compound E4-9-2

8-Isopropoxy-6,6-dimethyl-11-oxo-9-(1,2,3,6-tetrahydro-pyridin-4-yl)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1830] ##STR00267##

[1831] Under the same conditions as the method for synthesizing Compound A8-1, the title compound was prepared from Compound E4-9-1.

[1832] LCMS: m/z 426 [M+H].sup.+

[1833] HPLC retention time: 1.40 min (analysis condition S)

Example 253

Compound E4-10

9-Cyclopropyl-8-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1834] ##STR00268##

[1835] Under the same conditions as the method for synthesizing Compound E4-7-1, the title compound was prepared from Compound E3-1-1 and potassium cyclopropyltrifluoroborate.

[1836] LCMS: m/z 357 [M+H].sup.+

[1837] HPLC retention time: 2.62 min (analysis condition S)

Example 254

Compound E4-11

3-Cyano-8-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-9-carboxylic Acid

[1838] ##STR00269##

[1839] Under the same conditions as the method for synthesizing Compound B2-28, the title compound was prepared from Compound E3-1-1.

[1840] LCMS: m/z 361 [M+H].sup.+

[1841] HPLC retention time: 1.68 min (analysis condition S)

Example 255

Compound E5-1

9-Ethyl-8-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1842] ##STR00270##

[1843] The ethyl acetate suspension of 8-methoxy-6,6-dimethyl-11-oxo-9-vinyl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (Compound E4-3, 25 mg, 0.07 mmol) and palladium carbon (25 mg) were stirred at room temperature for 1 hr under hydrogen atmosphere. The reaction solution was filtered through Celite. The filtrate was concentrated under reduced pressure and the resulting residues were purified by high performance liquid chromatography to obtain the title compound (white solid, 3.2 mg, 13%).

[1844] LCMS: m/z 345 [M+H].sup.+

[1845] HPLC retention time: 2.62 min (analysis condition S)

Example 256

Compound E5-2

9-(2-Diethylamino-ethanesulfonyl)-8-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1846] ##STR00271##

[1847] Under the same conditions as the method for synthesizing Compound B3-8, the title compound was prepared from Compound E4-4.

[1848] LCMS: m/z 480 [M+H].sup.+

[1849] HPLC retention time: 1.97 min (analysis condition U)

Example 257

Compound E5-3

8-Methoxy-6,6-dimethyl-11-oxo-9-(propane-2-sulfonyl)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1850] ##STR00272##

[1851] Under the same conditions as the method for synthesizing Compound B3-8, the title compound was prepared from Compound E4-5.

[1852] LCMS: m/z 423 [M+H].sup.+

[1853] HPLC retention time: 2.40 min (analysis condition U)

Example 258

Compound E5-4

9-(1-Isopropyl-piperidin-4-yl)-8-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1854] ##STR00273##

[1855] Under the same conditions as the method for synthesizing Compound B3-32, the title compound was prepared from Compound E4-8-2 and acetone.

[1856] LCMS: m/z 442 [M+H].sup.+

[1857] HPLC retention time: 1.48 min (analysis condition S)

Example 259

Compound E5-5

8-Methoxy-6,6-dimethyl-9-(1-oxetan-3-yl-1,2,3,6-tetrahydro-pyridin-4-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1858] ##STR00274##

[1859] Under the same conditions as the method for synthesizing Compound B3-32, the title compound was prepared from Compound E4-7-2 and oxetan-3-one.

[1860] LCMS: m/z 454 [M+H].sup.+

[1861] HPLC retention time: 1.32 min (analysis condition S)

Example 260

Compound E5-6

8-Isopropoxy-6,6-dimethyl-9-(1-oxetan-3-yl-1,2,3,6-tetrahydro-pyridin-4-yl)-1-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1862] ##STR00275##

[1863] Under the same conditions as the method for synthesizing Compound B3-32, the title compound was prepared from Compound E4-9-2 and oxetan-3-one.

[1864] .sup.1H-NMR (270 MHz, DMSO-d.sub.6) : 12.71 (1H, s), 8.31 (1H, d, J=8.2 Hz), 7.99 (1H, s), 7.94 (1H, s), 7.58 (1H, d, J=7.6 Hz), 7.33 (1H, s), 5.84 (1.0H, m), 4.95 (1H, m), 4.56 (4H, dt, J=17.4, 6.3 Hz), 3.56 (1H, m), 3.01 (2H, br), 1.78 (6H, s), 1.34 (6H, d, J=5.9 Hz).

[1865] LCMS: m/z 482 [M+H].sup.+

[1866] HPLC retention time: 1.43 min (analysis condition S)

Example 261

Compound E5-7

9-(4-Isopropyl-piperazin-1-carbonyl)-8-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1867] ##STR00276##

[1868] Under the same conditions as the method for synthesizing Compound B3-15, the title compound was prepared from Compound E4-11 and 1-isopropylpiperazine.

[1869] LCMS: m/z 471 [M+H].sup.+

[1870] HPLC retention time: 1.18 min (analysis condition S)

Example 262

Compound E5-8

8-Methoxy-6,6-dimethyl-9-(morpholine-4-carbonyl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1871] ##STR00277##

[1872] Under the same conditions as the method for synthesizing Compound B3-15, the title compound was prepared from Compound E4-11 and morpholine.

[1873] LCMS: m/z 430 [M+H].sup.+

[1874] HPLC retention time: 1.68 min (analysis condition S)

Example 263

Compound E6-1

(3-Cyano-8-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-9-yl)-propionic Acid Methyl Ester

[1875] ##STR00278##

[1876] To the mixture of 9-ethynyl-8-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (Compound E4-2, 27 mg, 0.079 mmol), palladium (II) chloride (2.0 mg, 0.14 eq.), copper (II) chloride (25.0 mg, 2.2 eq.), and sodium acetate (14.1 mg, 2.13 eq.), methanol (1.5 mL) was added, and then the mixture was stirred at room temperature for 2 days under carbon monoxide atmosphere. The mixture was extracted with water and ethyl acetate and the insoluble matters were filtered off. The organic layer was washed with brine and dried over magnesium sulfate. The residues obtained after filtration and concentration under reduced pressure were washed with dichloromethane to obtain the title compound (13.9 mg, 44%).

[1877] LCMS: m/z 399 [M+H].sup.+

[1878] HPLC retention time: 2.81 min (analysis condition F)

Example 264

Compound E6-2

(3-Cyano-8-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-9-yl)-propynoic Acid

[1879] ##STR00279##

[1880] (3-Cyano-8-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-9-yl)-propynoic acid methyl ester (Compound E6-1, 15.2 mg, 0.038 mmol) was dissolved in a mixture solvent of methanol (1.5 mL) and THF (0.5 mL), added with 2 N aqueous solution of potassium hydroxide (5 drops), and then stirred at room temperature overnight. 0.5 N Hydrochloric acid was added to the reaction solution, which was then extracted with ethyl acetate. The organic layer was washed with brine and dried over magnesium sulfate. The solids obtained after filtration and concentration under reduced pressure were washed with dichloromethane and purified by HPLC to obtain the title compound (white solid, 9.6 mg, 66%).

[1881] LCMS: m/z 385 [M+H].sup.+

[1882] HPLC retention time: 2.35 min (analysis condition F)

Example 265

Compound E6-3

9-(3-Hydroxy-3-methyl-butyl)-8-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1883] ##STR00280##

[1884] 9-(3-Hydroxy-3-methyl-but-1-ynyl)-8-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (Compound E4-2-1, 21.0 mg, 0.0527 mmol) was dissolved in ethanol (15 mL) and N,N-dimethylacetamide (2 mL), added with 10% Pd/C (6.7 mg), and then stirred at room temperature overnight under hydrogen atmosphere. The reaction solution was filtered and concentrated under reduced pressure. The resulting residues were diluted with ethyl acetate, washed with brine, dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The resulting solid was washed with dichloromethane to obtain the title compound (yellow powder, 16.9 mg, 80%).

[1885] LCMS: m/z 403 [M+H].sup.+

[1886] HPLC retention time: 5.39 min (analysis condition H)

Example 266

Compound F1-1

4-(9-Bromo-3-cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl oxy)-piperidine-1-carboxylic Acid Tert-Butyl Ester

[1887] ##STR00281##

[1888] According to the same method as the method for synthesizing Compound A7-17, the title compound was prepared from Compound E3-2 and 4-trifluoromethanesulfonyloxy-piperidine-1-carboxylic acid tert-butyl ester.

[1889] LCMS: m/z 564, 566 [M+H].sup.+

[1890] HPLC retention time: 3.30 min (analysis condition S)

Example 267

Compound F1-2

9-Bromo-6,6-dimethyl-11-oxo-8-(piperidin-4-yl oxy)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1891] ##STR00282##

[1892] Under the same conditions as the method for synthesizing Compound A8-1, the title compound was prepared from Compound F1-1.

[1893] LCMS: m/z 464, 466 [M+H].sup.+

[1894] HPLC retention time: 1.52 min (analysis condition S)

Example 268

Compound F1-3

9-Bromo-8-(1-methanesulfonyl-piperidin-4-yl oxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1895] ##STR00283##

[1896] Under the same conditions as the method for synthesizing Compound A9-1, the title compound was prepared from Compound F1-2 and methanesulfonyl chloride.

[1897] LCMS: m/z 542, 544 [M+H].sup.+

[1898] HPLC retention time: 2.57 min (analysis condition S)

Example 269

Compound F1-4

9-Bromo-6,6-dimethyl-11-oxo-8-(tetrahydro-pyran-4-yl oxy)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1899] ##STR00284##

[1900] Under the same conditions as the method for synthesizing Compound A7-1, the title compound was prepared from Compound E3-2 and tetrahydropyran-4-ol.

[1901] LCMS: m/z 465, 467 [M+H].sup.+

[1902] HPLC retention time: 2.70 min (analysis condition S)

Example 270

Compound F2

Trifluoro-methanesulfonic Acid 9-bromo-3-cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl ester

[1903] ##STR00285##

[1904] Under the same conditions as the method for synthesizing Compound B1, the title compound was prepared from Compound E3-2.

[1905] .sup.1H-NMR (270 MHz, DMSO-d.sub.6) : 12.99 (1H, s), 8.51 (1H, s), 8.31 (1H, dd, J=8.2, 0.7 Hz), 8.17 (1H, s), 8.07 (1H, s), 7.67 (1H, dd, J=8.2, 1.4 Hz), 1.81 (6H, s).

[1906] LCMS: m/z 513, 515 [M+H].sup.+

[1907] HPLC retention time: 3.13 min (analysis condition S)

Example 271

Compound F3-1

9-Bromo-6,6-dimethyl-8-(1-oxetan-3-yl-piperidin-4-yl oxy)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1908] ##STR00286##

[1909] Under the same conditions as the method for synthesizing Compound B3-32, the title compound was prepared from Compound F1-2 and oxetan-3-one.

[1910] .sup.1H-NMR (400 MHz, DMSO-d.sub.6) : 8.29 (1H, d, 8 Hz), 8.29 (1H, s), 8.01 (1H, s), 7.60 (1H, d, 8 Hz), 7.55 (1H, s), 5.00-4.95 (1H, m), 4.55 (2H, dd, 8, 8 Hz), 4.44 (2H, dd, 8, 8 Hz), 2.52-2.46 (1H, m), 2.33-2.29 (2H, m), 1.96-1.94 (2H, m), 1.79 (8H, br. s)

[1911] LCMS: m/z 519, 521 [M+H].sup.+

[1912] HPLC retention time: 2.78 min (analysis condition W)

Example 272

Compound F3-2

9-Bromo-6,6-dimethyl-11-oxo-8-(4-pyrrolidin-1-yl-piperidin-1-yl)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1913] ##STR00287##

[1914] Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound F2 and 4-pyrrolidin-1-yl-piperidine.

[1915] LCMS: m/z 517, 519 [M+H].sup.+

[1916] HPLC retention time: 1.70 min (analysis condition S)

Example 273

Compound F3-3

9-Bromo-8-(4-methanesulfonyl-piperazin-1-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1917] ##STR00288##

[1918] Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound F2 and 1-methanesulfonylpiperazine.

[1919] LCMS: m/z 527, 529 [M+H].sup.+

[1920] HPLC retention time: 2.48 min (analysis condition S)

Example 274

Compound F3-4

9-Bromo-6,6-dimethyl-8-morpholin-4-yl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1921] ##STR00289##

[1922] Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound F2 and morpholine.

[1923] LCMS: m/z 450, 452 [M+H].sup.+

[1924] HPLC retention time: 2.65 min (analysis condition S)

Example 275

Compound F3-5

9-Bromo-8-[4-(2-hydroxy-ethyl)-piperazin-1-yl]-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1925] ##STR00290##

[1926] Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound F2 and 2-piperazin-1-yl ethanol.

[1927] .sup.1H-NMR (270 MHz, DMSO-d.sub.6) : 8.26 (2.0H, s+d), 7.97 (1H, s), 7.54 (1H, d, J=8.7 Hz), 7.43 (1H, s), 4.45 (1H, t, J=5.4 Hz), 3.55 (2H, q, J=5.8 Hz), 3.17 (4H, br), 2.66 (2H, br), 1.76 (6H, s).

[1928] LCMS: m/z 493, 495 [M+H].sup.+

[1929] HPLC retention time: 1.43 min (analysis condition S)

Example 276

Compound F3-6-1

[1-(9-Bromo-3-cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl)-piperidin-4-yl]-carbamic Acid Tert-Butyl Ester

[1930] ##STR00291##

[1931] Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound F2 and piperidin-4-yl-carbamic acid tert-butyl ester.

[1932] LCMS: m/z 563, 565 [M+H].sup.+

[1933] HPLC retention time: 3.05 min (analysis condition S)

Example 277

Compound F3-6-2

8-(4-Amino-piperidin-1-yl)-9-bromo-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1934] ##STR00292##

[1935] Under the same conditions as the method for synthesizing Compound A8-1, the title compound was prepared from Compound F3-6-1.

[1936] LCMS: m/z 463, 465 [M+H].sup.+

[1937] HPLC retention time: 1.47 min (analysis condition S)

Example 278

Compound F3-7

9-Bromo-8-(4-hydroxy-piperidin-1-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1938] ##STR00293##

[1939] Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound F2 and piperidin-4-ol.

[1940] LCMS: m/z 464, 466 [M+H].sup.+

[1941] HPLC retention time: 2.25 min (analysis condition S)

Example 279

Compound F3-8

9-Bromo-8-(4-isopropyl-piperazin-1-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1942] ##STR00294##

[1943] Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound F2 and 1-isopropylpiperazine.

[1944] LCMS: m/z 491, 493 [M+H].sup.+

[1945] HPLC retention time: 1.58 min (analysis condition S)

Example 280

Compound F3-9

9-Bromo-6,6-dimethyl-11-oxo-8-piperazin-1-yl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1946] ##STR00295##

[1947] Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound F2 and piperazine.

[1948] .sup.1H-NMR (DMSO-d.sub.6) : 8.30-8.24 (2H, m), 8.00 (1H, s), 7.63-7.58 (1H, m), 7.37 (1H, s), 3.10-3.01 (4H, m), 2.91-2.85 (4H, m), 1.76 (6H, s)

[1949] LCMS: m/z 449, 451 [M+H].sup.+

[1950] HPLC retention time: 1.45 min (analysis condition S)

Example 281

Compound F3-10

4-(9-Bromo-3-cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl)-piperazine-1-carboxylic Acid Tert-Butyl Ester

[1951] ##STR00296##

[1952] Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound F2 and piperazine-1-carboxylic acid tert-butyl ester.

[1953] LCMS: m/z 549, 551 [M+H].sup.+

[1954] HPLC retention time: 4.61 min (analysis condition W)

Example 282

Compound F3-11

9-Bromo-6,6-dimethyl-8-(4-morpholin-4-yl-piperidin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1955] ##STR00297##

[1956] Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound F2 and 4-piperidin-4-yl morpholine.

[1957] .sup.1H-NMR (DMSO-d.sub.6) : 8.30-8.24 (2H, m), 8.00 (1H, s), 7.59 (1H, d, J=8.2 Hz), 7.42 (1H, s), 3.66-3.45 (6H, m), 2.80 (2H, t, J=11.1 Hz), 2.38-2.28 (1H, m), 1.96-1.87 (2H, m), 1.75 (6H, s), 1.66-1.56 (2H, m)

[1958] LCMS: m/z 533, 535 [M+H].sup.+

[1959] HPLC retention time: 1.53 min (analysis condition S)

Example 283

Compound F4-1-1

9-Ethynyl-6,6-dimethyl-8-(1-oxetan-3-yl-piperidin-4-yl oxy)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1960] ##STR00298##

[1961] Under the same conditions as the method for synthesizing Compound F5-43, the title compound was prepared from Compound F3-1.

[1962] .sup.1H-NMR (400 MHz, DMSO-d.sub.6) : 8.30 (1H, d, 8 Hz), 8.17 (1H, s), 8.01 (1H, s), 7.60 (1H, d, 8 Hz), 7.50 (1H, s), 4.87-4.83 (1H, m), 4.55 (2H, dd, 4, 4 Hz), 4.45 (2H, dd, 4, 4 Hz), 3.44 (1H, ddd, 4, 4, 4 Hz), 2.33-2.24 (2H, m), 1.99-1.91 (2H, m), 1.78 (8H, br. s)

[1963] LCMS: m/z 466 [M+H].sup.+

[1964] HPLC retention time: 2.67 min (analysis condition W)

Example 284

Compound F4-1-2

9-Ethyl-6,6-dimethyl-8-(1-oxetan-3-yl-piperidin-4-yl oxy)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1965] ##STR00299##

[1966] Under the same conditions as the method for synthesizing Compound B3-13-1, the title compound was prepared from Compound F4-1-1.

[1967] LCMS: m/z 470 [M+H].sup.+

[1968] HPLC retention time: 2.74 min (analysis condition W)

Example 285

Compound F4-2

N-[1-(9-Bromo-3-cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl)-piperidin-4-yl]-methanesulfonamide

[1969] ##STR00300##

[1970] Under the same conditions as the method for synthesizing Compound A9-1, the title compound was prepared from Compound F3-6-2 and methanesulfonyl chloride.

[1971] LCMS: m/z 541, 543 [M+H].sup.+

[1972] HPLC retention time: 2.37 min (analysis condition S)

Example 286

Compound F4-3

9-Bromo-6,6-dimethyl-8-(4-oxetan-3-yl-piperazin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1973] ##STR00301##

[1974] Under the same conditions as the method for synthesizing Compound B3-32, the title compound was prepared from Compound F3-9 and 1-oxetan-3-one.

[1975] .sup.1H-NMR (270 MHz, DMSO-d.sub.6) : 12.83 (1H, br. s), 8.31-8.32 (1H, m), 8.27-8.29 (1H, m), 8.01-8.04 (1H, m), 7.59-7.64 (1H, m), 7.48 (1H, s), 4.59 (2H, dd, J=6.3, 6.3 Hz), 4.48 (2H, dd, J=6.3, 6.3 Hz), 3.52 (1H, t, J=6.3 Hz), 3.12-3.25 (4H, m), 2.44-2.54 (4H, m), 1.78 (6H, s).

[1976] LCMS: m/z 505, 507 [M+H].sup.+

[1977] HPLC retention time: 1.45 min (analysis condition S)

[1978] Hydrochloric Acid Salt of Compound F4-3

[1979] 9-Bromo-6,6-dimethyl-8-(4-oxetan-3-yl-piperazin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile was added with DMSO and 6 N hydrochloric acid (1.05 eq.) and dissolved therein. After freeze-drying, crystallization was performed by using ethanol comprising 25% water to obtain monohydrochloric acid salt of 9-bromo-6,6-dimethyl-8-(4-oxetan-3-yl-piperazin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile.

[1980] .sup.1H-NMR (270 MHz, DMSO-d.sub.6) : 12.91 (1H, br. s), 11.70 (1H, br. s), 8.32-8.29 (2H, m), 8.04 (1H, s), 7.64-7.62 (1H, m), 7.52 (1H, s), 4.89-4.62 (4H, br. m), 3.66-3.39 (1H, m), 3.31-3.05 (8H, br. m), 1.81 (6H, s)

[1981] LCMS: m/z 505, 507 [M+H].sup.+

Example 287

Compound F4-4

9-Bromo-8-{4-[2-(2-methoxy-ethoxy)-ethyl]-piperazin-1-yl}-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1982] ##STR00302##

[1983] Under the same conditions as the method for synthesizing Compound A7-17, the title compound was prepared from Compound F3-9 and 1-bromo-2-(2-methoxyethoxy)ethane.

[1984] LCMS: m/z 551, 553 [M+H].sup.+

[1985] HPLC retention time: 2.80 min (analysis condition W)

Example 288

Compound F4-5

9-Bromo-6,6-dimethyl-11-oxo-8-[4-(tetrahydro-pyran-4-yl)-piperazin-1-yl]-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1986] ##STR00303##

[1987] Under the same conditions as the method for synthesizing Compound B3-32, the title compound was prepared from Compound F3-9 and tetrahydropyran-4-one.

[1988] LCMS: m/z 533, 535 [M+H].sup.+

[1989] HPLC retention time: 2.67 min (analysis condition W)

Example 289

Compound F4-6

9-Bromo-6,6-dimethyl-11-oxo-8-[4-(tetrahydro-thiopyran-4-yl)-piperazin-1-yl]-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1990] ##STR00304##

[1991] Under the same conditions as the method for synthesizing Compound B3-32, the title compound was prepared from Compound F3-9 and tetrahydrothiopyran-4-one.

[1992] LCMS: m/z 549, 551 [M+H].sup.+

[1993] HPLC retention time: 2.86 min (analysis condition W)

Example 290

Compound F4-7

9-Bromo-8-[4-(1,1-dioxo-hexahydro-16-thiopyran-4-yl)-piperazin-1-yl]-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1994] ##STR00305##

[1995] Under the same conditions as the method for synthesizing Compound B3-8, the title compound was prepared from Compound F4-6.

[1996] LCMS: m/z 581, 583 [M+H].sup.+

[1997] HPLC retention time: 2.66 min (analysis condition W)

Example 291

Compound F4-8

9-Bromo-8-(4-cyclopropylmethyl-piperazin-1-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[1998] ##STR00306##

[1999] Under the same conditions as the method for synthesizing Compound A7-17, the title compound was prepared from Compound F3-9 and bromomethylcyclopropane.

[2000] LCMS: m/z 503, 505 [M+H].sup.+

[2001] HPLC retention time: 2.81 min (analysis condition W)

Example 292

Compound F4-9

9-Bromo-8-(4-cyclopropyl-piperazin-1-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2002] ##STR00307##

[2003] Under the same conditions as the method for synthesizing Compound B3-32, the title compound was prepared from Compound F3-9 and (1-ethoxy-cyclopropoxy)-trimethyl-silane.

[2004] .sup.1H-NMR (270 MHz, DMSO-d.sub.6) : 8.22-8.30 (2H, m), 8.00 (1H, s), 7.56 (1H, d, J=7.9 Hz), 7.43 (1H, s), 3.30 (1H, d, J=5.8 Hz), 3.11 (4H, s), 2.75 (4H, s), 1.75 (6H, s), 0.47 (2H, d, J=5.8 Hz), 0.34 (2H, d, J=5.8 Hz)

[2005] LCMS: m/z 489, 491 [M+H].sup.+

[2006] HPLC retention time: 1.68 min (analysis condition S)

Example 293

Compound F4-10

9-Bromo-8-(4-cyclobutyl-piperazin-1-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2007] ##STR00308##

[2008] Under the same conditions as the method for synthesizing Compound B3-32, the title compound was prepared from Compound F3-9 and cyclobutanone.

[2009] .sup.1H-NMR (400 MHz, DMSO-d.sub.6) : 8.23-8.29 (2H, m), 8.00 (1H, s), 7.55 (1H, d, 7.9 Hz), 7.45 (1H, s), 4.04-4.15 (1H, m), 3.10-3.20 (4H, m), 2.39-2.48 (4H, m), 1.97-2.06 (2H, m), 1.78-1.88 (2H, m), 1.77 (6H, s), 1.61-1.72 (2H, m)

[2010] LCMS: m/z 503, 505 [M+H].sup.+

[2011] HPLC retention time: 2.78 min (analysis condition W)

Example 294

Compound F5-1

9-Ethynyl-8-(4-methanesulfonyl-piperazin-1-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2012] ##STR00309##

[2013] Under the same conditions as the method for synthesizing Compound F5-43, the title compound was prepared from Compound F3-3.

[2014] .sup.1H-NMR (270 MHz, DMSO-d.sub.6) : 12.78 (1H, s), 8.31 (1H, dd, J=8.1, 0.7 Hz), 8.19 (1H, s), 8.02 (1H, dd, J=1.4, 0.7 Hz), 7.61 (1H, dd, J=8.2, 1.4 Hz), 7.33 (1H, s), 4.55 (1H, s), 3.43 (4H, br), 2.98 (3H, s), 1.79 (6H, s).

[2015] LCMS: m/z 473 [M+H].sup.+

[2016] HPLC retention time: 2.27 min (analysis condition S)

Example 295

Compound F5-2

N-[1-(3-Cyano-9-ethynyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl)-piperidin-4-yl]-methanesulfonamide

[2017] ##STR00310##

[2018] Under the same conditions as the method for synthesizing Compound F5-43, the title compound was prepared from Compound F4-2.

[2019] .sup.1H-NMR (270 MHz, DMSO-d.sub.6) : 12.98 (1H, s), 8.30 (1H, d, J=8.1 Hz), 8.15 (1H, s), 8.02 (1H, s), 7.61 (1H, d, J=7.9 Hz), 7.23 (2H, s+d), 4.55 (1H, s), 3.79 (2H, brd), 2.95 (4H, br), 1.96 (2H, brd), 1.78 (3H, s), 1.65 (2H, brd).

[2020] LCMS: m/z 487 [M+H].sup.+

[2021] HPLC retention time: 2.15 min (analysis condition S)

Example 296

Compound F5-3

6,6-Dimethyl-11-oxo-8-(4-pyrrolidin-1-yl-piperidin-1-yl)-6,11-dihydro-5H-benzo[b]carbazole-3,9-dicarbonitrile

[2022] ##STR00311##

[2023] Under the same conditions as the method for synthesizing Compound A5-2, the target compound was prepared from Compound F3-2.

[2024] .sup.1H-NMR (270 MHz, DMSO-d.sub.6) : 8.33 (1H, d, J=1.3 Hz), 8.27 (1H, dd, J=7.7, 1.3 Hz), 8.00 (1H, s), 7.57 (1H, d, J=7.7 Hz), 7.40 (1H, s), 3.74 (2H, m), 3.19-3.33 (1H, m), 2.98-3.12 (2H, m), 2.35-2.62 (2H, m), 2.11-2.29 (2H, m), 1.89-2.06 (2H, m), 1.78 (6H, s), 1.54-1.70 (6H, m).

[2025] LCMS: m/z 464 [M+H].sup.+

[2026] HPLC retention time: 1.55 min (analysis condition S)

Example 297

Compound F5-4

9-Ethynyl-6,6-dimethyl-11-oxo-8-(4-pyrrolidin-1-yl-piperidin-1-yl)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2027] ##STR00312##

[2028] Under the same conditions as the method for synthesizing Compound E4-2-1 and Compound E4-2-2, the title compound was prepared from Compound F3-2.

[2029] .sup.1H-NMR (270 MHz, DMSO-d.sub.6) : 8.29 (1H, d, J=8.2 Hz), 8.14 (1H, s), 8.00 (1H, s), 7.58 (1H, dd, J=8.1, 1.3 Hz), 7.24 (1H, s), 4.50 (1H, s), 3.70-3.83 (2H, m), 3.34-3.48 (1H, m), 2.83-2.98 (2H, m), 2.45-2.58 (2H, m), 2.10-2.23 (2H, m), 1.90-2.03 (2H, m), 1.76 (6H, s), 1.51-1.74 (6H, m).

[2030] LCMS: m/z 463 [M+H].sup.+

[2031] HPLC retention time: 1.60 min (analysis condition S)

Example 298

Compound F5-5

9-Ethynyl-6,6-dimethyl-8-morpholin-4-yl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2032] ##STR00313##

[2033] Under the same conditions as the method for synthesizing Compound E4-2-1 and Compound E4-2-2, the title compound was prepared from Compound F3-4.

[2034] .sup.1H-NMR (400 MHz, DMSO-d.sub.6) : 12.82 (1H, s), 8.31 (1H, d, J=7.9 Hz), 8.18 (1H, s), 8.02 (1H, s), 7.61 (1H, d, J=7.9 Hz), 7.28 (1H, s), 4.53 (1H, s), 3.80 (4 H, s), 3.36 (4H, s), 1.79 (6H, s).

[2035] LCMS: m/z 396 [M+H].sup.+

[2036] HPLC retention time: 2.32 min (analysis condition S)

Example 299

Compound F5-6

9-(3-Dimethylamino-prop-1-ynyl)-6,6-dimethyl-8-morpholin-4-yl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2037] ##STR00314##

[2038] Under the same conditions as the method for synthesizing Compound E4-2-1, the title compound was prepared from Compound F3-4 and 3-dimethylaminopropyne.

[2039] .sup.1H-NMR (270 MHz, CDCl.sub.3) : 8.52 (1H, d, J=7.8 Hz), 8.47 (1H, s), 7.76 (1H, s), 7.56 (1H, d, J=7.8 Hz), 7.03 (1H, s), 3.92 (4H, m), 3.55 (2H, s), 3.39 (4H, m), 2.37 (6H, s), 1.83 (6H, s)

[2040] LCMS: m/z 453 [M+H].sup.+

Example 300

Compound F5-7

6,6-Dimethyl-8-morpholin-4-yl-9-(3-morpholin-4-yl-prop-1-ynyl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2041] ##STR00315##

[2042] To 9-bromo-6,6-dimethyl-8-morpholin-4-yl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (Compound F3-4, 30 mg, 0.067 mmol), 3-bromopropyne (0.01 ml, 0.13 mmol), morpholine (0.029 ml, 0.33 mmol), X-Phos (4.8 mg, 15% mol), PdCl.sub.2 (CH.sub.3CN).sub.2 (0.9 mg, 5% mol) and cesium carbonate (87 mg, 0.27 mmol), acetonitrile (2 ml) was added and the mixture was stirred at 80 C. for 2 hr. The reaction solution was added to water, and then extracted with dichloromethane. The organic layer was dried over sodium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (dichloromethane/methanol) to obtain the target compound (pale brown solid, 18 mg, 64%).

[2043] .sup.1H-NMR (270 MHz, DMSO-d.sub.6) : 8.29 (1H, d, J=7.8 Hz), 8.14 (1H, s), 8.00 (1H, s), 7.59 (1H, d, J=7.8 Hz), 7.27 (1H, s), 3.79 (4H, m), 3.64 (4H, m), 3.61 (2H, s), 3.33 (4H, m), 2.56 (4H, m), 1.77 (6H, s)

[2044] LCMS: m/z 495 [M+H].sup.+

Example 301

Compound F5-8

6,6-Dimethyl-8-morpholin-4-yl-11-oxo-9-pent-1-ynyl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2045] ##STR00316##

[2046] Under the same conditions as the method for synthesizing Compound E4-2-1, the title compound was prepared from Compound F3-4 and 1-pentyne.

[2047] LCMS: m/z 438 [M+H].sup.+

[2048] HPLC retention time: 2.88 min (analysis condition S)

Example 302

Compound F5-9

9-(3-Methoxy-prop-1-ynyl)-6,6-dimethyl-8-morpholin-4-yl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2049] ##STR00317##

[2050] Under the same conditions as the method for synthesizing Compound E4-2-1, the title compound was prepared from Compound F3-4 and 3-methoxypropyne.

[2051] .sup.1H-NMR (270 MHz, DMSO-d.sub.6) : 8.30 (1H, d, J=7.8 Hz), 8.15 (1H, s), 8.01 (1H, s), 7.60 (1H, d, J=7.8 Hz), 7.28 (1H, s), 4.41 (2H, s), 3.79 (4H, m), 3.37 (3H, s), 3.34 (4H, m), 1.78 (6H, s)

[2052] LCMS: m/z 440 [M+H].sup.+

Example 303

Compound F5-10

9-[3-(4-Cyclopropyl-piperazin-1-yl)-prop-1-ynyl]-6,6-dimethyl-8-morpholin-4-yl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2053] ##STR00318##

[2054] Under the same conditions as the method for synthesizing Compound F5-7, the title compound was prepared from Compound F3-4 and 3-bromopropyne and 4-cyclopropylpiperazine.

[2055] LCMS: m/z 534 [M+H].sup.+

[2056] HPLC retention time: 1.40 min (analysis condition S)

Example 304

Compound F5-11

6,6-Dimethyl-9-(1-methyl-1H-pyrazol-4-yl)-8-morpholin-4-yl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2057] ##STR00319##

[2058] Under the same conditions as the method for synthesizing Compound E4-7-1, the title compound was prepared from Compound F3-4 and 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole.

[2059] .sup.1H-NMR (400 MHz, DMSO-d.sub.6) : 8.29 (1H, d, J=7.8 Hz), 8.22 (1H, s), 8.09 (1H, s), 7.99 (1H, s), 7.95 (1H, s), 7.56-7.61 (1H, m), 7.36 (1H, s), 3.90 (3H, s), 3.73 (4H, s), 2.95 (4H, s), 1.77 (6H, s).

[2060] LCMS: m/z 452 [M+H].sup.+

[2061] HPLC retention time: 2.18 min (analysis condition U)

Example 305

Compound F5-12

9-Cyclopropyl-6,6-dimethyl-8-morpholin-4-yl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2062] ##STR00320##

[2063] Under the same conditions as the method for synthesizing Compound E4-7-1, the title compound was prepared from Compound F3-4 and potassium cyclopropyltrifluoroborate.

[2064] .sup.1H-NMR (270 MHz, CD.sub.3OD+CDCl.sub.3) : 8.45 (1H, d, J=7.8 Hz), 7.83 (2H, m), 7.54 (1H, d, J=7.8 Hz), 7.20 (1H, s), 3.96 (4H, m), 3.24 (4H, m), 2.25 (1H, m), 1.80 (6H, s), 1.09 (2H, m), 0.93 (2H, m)

[2065] LCMS: m/z 412 [M+H].sup.+

Example 306

Compound F5-13

6,6-Dimethyl-8-morpholin-4-yl-11-oxo-9-vinyl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2066] ##STR00321##

[2067] Under the same conditions as the method for synthesizing Compound B2-24, the title compound was prepared from Compound F3-4 and potassium vinyltrifluoroborate.

[2068] LCMS: m/z 398 [M+H].sup.+

[2069] HPLC retention time: 2.67 min (analysis condition U)

Example 307

Compound F5-14

9-Ethynyl-8-(4-isopropyl-piperazin-1-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2070] ##STR00322##

[2071] Under the same conditions as the method for synthesizing Compound F5-43, the title compound was prepared from Compound F3-8.

[2072] .sup.1H-NMR (400 MHz, DMSO-d.sub.6) : 12.73 (1H, s), 8.31 (1H, d, J=9.1 Hz), 8.16 (1H, d, J=1.2 Hz), 8.00 (1H, s), 7.60 (1H, d, J=7.9 Hz), 7.25 (1H, s), 4.50 (1H, d, J=1.8 Hz), 2.72 (1H, m), 2.65 (4H, s), 1.78 (6H, s), 1.04 (6H, d, J=5.5 Hz).

[2073] LCMS: m/z 437 [M+H].sup.+

[2074] HPLC retention time: 1.48 min (analysis condition S)

Example 308

Compound F5-15-1

4-(3-Cyano-9-cyclopropyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl)-piperazine-1-carboxylic Acid Tert-Butyl Ester

[2075] ##STR00323##

[2076] Under the same conditions as the method for synthesizing Compound E4-7-1, the title compound was prepared from Compound F3-10 and potassium cyclopropyltrifluoroborate.

[2077] .sup.1H-NMR (400 MHz, DMSO-d.sub.6) : 8.55 (1H, s), 8.28-8.25 (1H, m), 7.98-7.95 (1H, m), 7.62 (1H, s), 7.32 (1H, s), 3.56-3.53 (4 h, m), 3.09-3.07 (4H, m), 2.22-2.18 (1H, m), 1.73 (6H, br s), 1.44 (9H, s), 1.08-1.05 (2H, m), 0.77-0.76 (2H, m)

[2078] LCMS: m/z 511 [M+H].sup.+

[2079] HPLC retention time: 4.50 min (analysis condition W)

Example 309

Compound F5-15-2

9-Cyclopropyl-6,6-dimethyl-11-oxo-8-piperazin-1-yl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2080] ##STR00324##

[2081] Under the same conditions as the method for synthesizing Compound A8-1, the title compound was prepared from Compound F5-15-1.

[2082] LCMS: m/z 411 [M+H].sup.+

[2083] HPLC retention time: 2.67 min (analysis condition W)

Example 310

Compound F5-16

9-Ethynyl-6,6-dimethyl-8-(4-oxetan-3-yl-piperazin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2084] ##STR00325##

[2085] Under the same conditions as the method for synthesizing Compound F5-43, the title compound was prepared from Compound F4-3.

[2086] .sup.1H-NMR (270 MHz, DMSO-d.sub.6) : 12.77 (1H, br. s), 8.31 (1H, d, J=8.2 Hz), 8.16 (1H, s), 8.02 (1H, s), 7.61 (1H, dd, J=8.2, 1.3 Hz), 7.27 (1H, s), 4.59 (2H, dd, J=6.6, 6.6 Hz), 4.51 (1H, s), 4.49 (2H, dd, J=6.6, 6.6 Hz), 3.51 (1H, t, J=6.6 Hz), 3.35-3.43 (4H, m), 2.43-2.50 (4H, s), 1.78 (6H, s).

[2087] LCMS: m/z 451 [M+H].sup.+

[2088] HPLC retention time: 1.40 min (analysis condition S)

Example 311

Compound F5-17

6,6-Dimethyl-8-(4-oxetan-3-yl-piperazin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3,9-dicarbonitrile

[2089] ##STR00326##

[2090] According to the same method as the method for synthesizing Compound A5-2, the title compound was prepared from Compound F4-3.

[2091] .sup.1H-NMR (270 MHz, DMSO-d.sub.6) : 12.84 (1H, br. s), 8.36 (1H, s), 8.32-8.29 (1H, d, 8.08 Hz), 8.04 (1H, s), 7.65-7.62 (1H, d, 8.08 Hz), 7.44 (1H, s), 4.62-4.57 (2H, m), 4.52-4.47 (2H, m), 3.81-3.78 (2H, t, 4.61 Hz), 3.57-3.50 (1H, m), 3.43 (4H, m) 2.51 (4H, m), 1.80 (6H, s)

[2092] LCMS: m/z 452 [M+H].sup.+

Example 312

Compound F5-18

9-(3-Methoxy-prop-1-ynyl)-6,6-dimethyl-8-(4-oxetan-3-yl-piperazin-1-yl)-1-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2093] ##STR00327##

[2094] Under the same conditions as the method for synthesizing Compound E4-2-1, the title compound was prepared from Compound F4-3 and 3-methoxypropyne.

[2095] .sup.1H-NMR (270 MHz, DMSO-d.sub.6) : 12.77 (1H, br. s), 8.32-8.29 (1H, d, 8.08 Hz), 8.13 (1H, s), 8.01 (1H, s), 7.62-7.59 (1H, d, 8.08 Hz), 7.27 (1H, s), 4.62-4.57 (2H, m), 4.52-4.47 (2H, m), 4.39 (2H, s), 3.53-3.47 (1H, m), 3.38 (4H, m), 3.36 (3H, s), 2.51 (4H, m), 1.77 (6H, s)

[2096] LCMS: m/z 495 [M+H].sup.+

Example 313

Compound F5-19

9-(3-Dimethylamino-prop-1-ynyl)-6,6-dimethyl-8-(4-oxetan-3-yl-piperazin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2097] ##STR00328##

[2098] Under the same conditions as the method for synthesizing Compound E4-2-1, the title compound was prepared from Compound F4-3 and dimethyl-prop-2-ynylamine.

[2099] LCMS: m/z 508 [M+H].sup.+

[2100] HPLC retention time: 1.07 min (analysis condition S)

Example 314

Compound F5-20

6,6-Dimethyl-8-(4-oxetan-3-yl-piperazin-1-yl)-9-[3-(4-oxetan-3-yl-piperazin-1-yl)-prop-1-ynyl]-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2101] ##STR00329##

[2102] Under the same conditions as the method for synthesizing Compound F5-7, the title compound was prepared from Compound F4-3, 3-bromopropyne and 4-oxetan-3-yl-piperazine.

[2103] .sup.1H-NMR (270 MHz, DMSO-d.sub.6) : 8.30 (1H, d, J=7.8 Hz), 8.12 (1H, s), 8.00 (1H, s), 7.59 (1H, d, J=7.8 Hz), 7.26 (1H, s), 4.60-4.42 (8H, m), 3.61 (2H, s), 3.60-3.30 (6H, m), 2.60-2.30 (12H, m), 1.77 (6H, s)

[2104] LCMS: m/z 605 [M+H].sup.+

Example 315

Compound F5-21

9-Cyclopentylethynyl-6,6-dimethyl-8-(4-oxetan-3-yl piperazin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2105] ##STR00330##

[2106] Under the same conditions as the method for synthesizing Compound E4-2-1, the title compound was prepared from Compound F4-3 and cyclopentylacetylene.

[2107] LCMS: m/z 519 [M+H].sup.+

[2108] HPLC retention time: 1.80 min (analysis condition S)

Example 316

Compound F5-22

6,6-Dimethyl-8-(4-oxetan-3-yl-piperazin-1-yl)-11-oxo-9-prop-1-ynyl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2109] ##STR00331##

[2110] Under the same conditions as the method for synthesizing Compound E4-2-1, the title compound was prepared from Compound F4-3 and propyne.

[2111] .sup.1H-NMR (400 MHz, CD.sub.3OD) : 8.37 (1H, d, J=8.2 Hz), 8.18 (1H, s), 7.84 (1H, s), 7.53 (1H, d, J=8.2 Hz), 7.19 (1H, s), 4.70-4.77 (2H, m), 4.62-4.68 (2H, m), 3.57-3.63 (1H, m), 3.38-3.45 (4H, m), 2.54-2.61 (4H, m), 2.10 (3H, s), 1.79 (6H, s)

[2112] LCMS: m/z 465 [M+H].sup.+

[2113] HPLC retention time: 1.90 min (analysis condition U)

Example 317

Compound F5-23

9-(3-Hydroxy-prop-1-ynyl)-6,6-dimethyl-8-(4-oxetan-3-yl-piperazin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2114] ##STR00332##

[2115] Under the same conditions as the method for synthesizing Compound E4-2-1, the TMS complex of the title compound was prepared from Compound F4-3 and trimethylprop-2-ynyloxysilane. By treating the resulting TMS complex with tetrabutylammonium fluoride, the title compound was obtained.

[2116] LCMS: m/z 481 [M+H].sup.+

[2117] HPLC retention time: 1.30 min (analysis condition S)

Example 318

Compound F5-24

6,6-Dimethyl-9-(4-methyl-pent-1-ynyl)-8-(4-oxetan-3-yl-piperazin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2118] ##STR00333##

[2119] Under the same conditions as the method for synthesizing Compound E4-2-1, the title compound was prepared from Compound F4-3 and 4-methylpent-1-yne.

[2120] .sup.1H-NMR (270 MHz, DMSO-d.sub.6) : 12.75 (1H, br. s), 8.32-8.29 (1H, d, 8.08 Hz), 8.08 (1H, s), 8.01 (1H, s), 7.62-7.59 (1H, m), 7.23 (1H, s), 4.61-4.57 (2H, m), 4.51-4.46 (2H, m), 3.51-3.47 (1H, m), 3.37 (4H, m), 2.46 (4H, m), 2.41-2.39 (2H, d, 5.94 Hz), 1.92-1.80 (1H, m), 1.77 (6H, s), 1.04 (3H, s), 1.01 (3H, s)

[2121] LCMS: m/z 507 [M+H].sup.+

Example 319

Compound F5-25

9-Cyclopropylethynyl-6,6-dimethyl-8-(4-oxetan-3-yl-piperazin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2122] ##STR00334##

[2123] Under the same conditions as the method for synthesizing Compound E4-2-1, the title compound was prepared from Compound F4-3 and ethynylcyclopropane.

[2124] .sup.1H-NMR (270 MHz, DMSO-d.sub.6) : 12.74 (1H, br. s), 8.32-8.29 (1H, d, 8.08 Hz), 8.05 (1H, s), 8.00 (1H, s), 7.62-7.58 (1H, m), 7.21 (1H, s), 4.62-4.57 (2H, m), 4.51-4.47 (2H, m), 3.53-3.48 (1H, m), 3.34 (4H, m), 2.46 (4H, m), 1.76 (6H, s), 1.64-1.58 (1H, m), 0.97-0.89 (2H, m), 0.76-0.70 (2H, m)

[2125] LCMS: m/z 491 [M+H].sup.+

Example 320

Compound F5-26

6,6-Dimethyl-9-(3-morpholin-4-yl-prop-1-ynyl)-8-(4-oxetan-3-yl-piperazin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2126] ##STR00335##

[2127] Under the same conditions as the method for synthesizing Compound F5-7, the title compound was prepared from Compound F4-3, 3-bromopropyne and morpholine.

[2128] .sup.1H-NMR (270 MHz, DMSO-d.sub.6) : 8.29 (1H, d, J=7.8 Hz), 8.13 (1H, s), 8.02 (1H, s), 7.59 (1H, d, J=7.8 Hz), 7.25 (1H, s), 4.61-4.48 (4H, m), 3.64-3.32 (11H, m), 2.60-2.40 (8H, m), 1.78 (6H, s)

[2129] LCMS: m/z 550 [M+H].sup.+

Example 321

Compound F5-27

6,6-Dimethyl-8-(4-oxetan-3-yl-piperazin-1-yl)-11-oxo-9-pent-1-ynyl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2130] ##STR00336##

[2131] Under the same conditions as the method for synthesizing Compound E4-2-1, the title compound was prepared from Compound F4-3 and 1-pentyne.

[2132] .sup.1H-NMR (400 MHz, DMSO-d.sub.6) : 12.72 (1H, br. s), 8.28 (1H, d, 8.1 Hz), 8.06 (1H, s), 7.98 (1H, s), 7.58 (1H, d, 8.1 Hz), 7.21 (1H, s), 4.60-4.43 (4H, m), 3.53-3.44 (1H, m), 3.39-3.32 (2H, m), 1.75 (6H, s), 1.60-1.53 (4H, m), 1.01 (3H, t, 7.3 Hz)

[2133] LCMS: m/z 493 [M+H].sup.+

[2134] HPLC retention time: 2.17 min (analysis condition U)

Example 322

Compound F5-28

6,6-Dimethyl-9-(5-methyl-hex-1-ynyl)-8-(4-oxetan-3-yl-piperazin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2135] ##STR00337##

[2136] Under the same conditions as the method for synthesizing Compound E4-2-1, the title compound was prepared from Compound F4-3 and 5-methylhex-1-yne.

[2137] LCMS: m/z 521 [M+H].sup.+

[2138] HPLC retention time: 2.37 min (analysis condition U)

Example 323

Compound F5-29

9-(3-Diethylamino-prop-1-ynyl)-6,6-dimethyl-8-(4-oxetan-3-yl-piperazin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2139] ##STR00338##

[2140] Under the same conditions as the method for synthesizing Compound E4-2-1, the title compound was prepared from Compound F4-3 and 3-diethylaminopropyne.

[2141] LCMS: m/z 536 [M+H].sup.+

[2142] HPLC retention time: 1.13 min (analysis condition S)

Example 324

Compound F5-30

9-[3-(Benzyl-ethyl-amino)-prop-1-ynyl]-6,6-dimethyl-8-(4-oxetan-3-yl-piperazin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2143] ##STR00339##

[2144] Under the same conditions as the method for synthesizing Compound E4-2-1, the title compound was prepared from Compound F4-3 and 3-benzyl-3-ethylaminopropyne.

[2145] LCMS: m/z 584 [M+H].sup.+

[2146] HPLC retention time: 1.32 min (analysis condition S)

Example 325

Compound F5-31

9-[3-(1,1-Dioxo-16-thiomorpholin-4-yl)-prop-1-ynyl]-6,6-dimethyl-8-(4-oxetan-3-yl-piperazin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2147] ##STR00340##

[2148] Under the same conditions as the method for synthesizing Compound E4-2-1, the title compound was prepared from Compound F4-3 and 3-(1,1-dioxo-1l6-thiomorpholin-4-yl)-propyne.

[2149] LCMS: m/z 598 [M+H].sup.+

[2150] HPLC retention time: 1.35 min (analysis condition S)

Example 326

Compound F5-32

9-Isopropenyl-6,6-dimethyl-8-(4-oxetan-3-yl-piperazin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2151] ##STR00341##

[2152] Under the same conditions as the method for synthesizing Compound E4-7-1, the title compound was prepared from Compound F4-3 and 2-isopropenyl-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane.

[2153] .sup.1H-NMR (270 MHz, CD.sub.3OD+CDCl.sub.3) : 8.44 (1H, d, J=7.8 Hz), 8.09 (1H, s), 7.83 (1H, s), 7.54 (1H, d, J=7.8 Hz), 7.18 (1H, s), 5.24-5.20 (2H, m), 4.81-4.68 (4H, m), 3.66 (1H, m), 3.30 (4H, m), 2.57 (4H, m), 2.21 (3H, s), 1.82 (6H, s)

[2154] LCMS: m/z 467 [M+H].sup.+

Example 327

Compound F5-33

6,6,9-Trimethyl-8-(4-oxetan-3-yl-piperazin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2155] ##STR00342##

[2156] Under the same conditions as the method for synthesizing Compound F5-47, the title compound was prepared from Compound F4-3.

[2157] .sup.1H-NMR (270 MHz, DMSO-d.sub.6) : 12.71 (1H, br. s), 8.33-8.31 (1H, d, 8.08 Hz), 8.01 (1H, s), 7.97 (1H, s), 7.62-7.59 (1H, m), 7.32 (1H, s), 4.61-4.57 (2H, m), 4.51-4.47 (2H, m), 3.55-3.49 (1H, m), 3.05 (4H, m), 2.47 (4H, m), 2.33 (3H, s), 1.76 (6H, s)

[2158] LCMS: m/z 441 [M+H].sup.+

Example 328

Compound F5-34

9-Cyclopropyl-6,6-dimethyl-8-(4-oxetan-3-yl-piperazin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2159] ##STR00343##

[2160] Under the same conditions as the method for synthesizing Compound B3-32, the title compound was prepared from Compound F5-15-2 and oxetan-3-one.

[2161] .sup.1H-NMR (400 MHz, DMSO-d.sub.6) : 8.32-8.29 (1H, m), 8.00-7.99 (1H, m), 7.62-7.58 (2H, m), 7.32-7.31 (1H, m), 4.61-4.57 (2H, m), 4.52-4.49 (2H, m), 3.53 (1H, br. s), 3.18 (4H, br. s), 1.75 (6H, s), 1.25-1.23 (1H, m), 1.09-1.04 (2H, m), 0.79-0.75 (2H, m)

[2162] LCMS: m/z 467 [M+H].sup.+

[2163] HPLC retention time: 2.74 min (analysis condition W)

Example 329

Compound F5-35

6,6-Dimethyl-9-(1-methyl-1H-pyrazol-4-yl)-8-(4-oxetan-3-yl-piperazin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2164] ##STR00344##

[2165] Under the same conditions as the method for synthesizing Compound E4-7-1, the title compound was prepared from Compound F4-3 and 1-methyl-4-(4,4,5,5-tetramethyl-[1,3,2] dioxaborolan-2-yl)-1H-pyrazole.

[2166] LCMS: m/z 507 [M+H].sup.+

[2167] HPLC retention time: 1.75 min (analysis condition U)

Example 330

Compound F5-36-1

4-[3-Cyano-6,6-dimethyl-11-oxo-8-(4-pyrrolidin-1-yl-piperidin-1-yl)-6,11-dihydro-5H-benzo[b]carbazol-9-yl]-3,6-dihydro-2H-pyridine-1-carboxylic Acid Tert-Butyl Ester

[2168] ##STR00345##

[2169] Under the same conditions as the method for synthesizing Compound E4-7-1, the title compound was prepared from Compound F3-2.

[2170] LCMS: m/z 621 [M+H].sup.+

[2171] HPLC retention time: 2.58 min (analysis condition U)

Example 331

Compound F5-36-2

6,6-Dimethyl-11-oxo-8-(4-pyrrolidin-1-yl-piperidin-1-yl)-9-(1,2,3,6-tetrahydro-pyridin-4-yl)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2172] ##STR00346##

[2173] Under the same conditions as the method for synthesizing Compound A8-1, the title compound was prepared from Compound F5-36-1.

[2174] LCMS: m/z 520 [M+H].sup.+

[2175] HPLC retention time: 1.82 min (analysis condition U)

Example 332

Compound F5-37

8-(4-Cyclopropyl-piperazin-1-yl)-9-ethynyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2176] ##STR00347##

[2177] Under the same conditions as the method for synthesizing Compound F5-43, the title compound was prepared from Compound F4-9.

[2178] .sup.1H-NMR (270 MHz, DMSO-d.sub.6) : 12.76 (1H, br. s), 8.31 (1H, d, J=8.1 Hz), 8.15 (1H, s), 8.01 (1H, s), 7.61 (1H, dd, J=8.1, 1.5 Hz), 7.24 (1H, s), 4.52 (1H, s), 3.28-3.36 (4H, m), 3.17 (1H, d, J=5.3 Hz), 2.70-2.77 (4H, m), 1.76 (6H, s), 0.47 (2H, d, J=5.3 Hz), 0.36 (2H, d, J=5.3 Hz).

[2179] LCMS: m/z 435 [M+H].sup.+

[2180] HPLC retention time: 1.57 min (analysis condition S)

Example 333

Compound F5-38

8-(4-Cyclopropyl-piperazin-1-yl)-6,6-dimethyl-11-oxo-9-prop-1-ynyl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2181] ##STR00348##

[2182] Under the same conditions as the method for synthesizing Compound E4-2-1, the title compound was prepared from Compound F4-9 and propyne.

[2183] .sup.1H-NMR (270 MHz, DMSO-d.sub.6) : 12.76 (1H, br. s), 8.31-8.28 (1H, d, 8.08 Hz), 8.06 (1H, s), 8.00 (1H, s), 7.60-7.57 (1H, m), 7.19 (1H, s), 3.29 (4H, m), 2.74 (4H, m), 2.55 (1H, m), 2.13 (3H, s), 1.75 (6H, s), 0.51-0.43 (2H, m), 0.38-0.32 (2H, m)

[2184] LCMS: m/z 449 [M+H].sup.+

Example 334

Compound F5-39

8-(4-Cyclopropyl-piperazin-1-yl)-6,6-dimethyl-11-oxo-9-phenyl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2185] ##STR00349##

[2186] Under the same conditions as the method for synthesizing Compound E4-7-1, the title compound was prepared from Compound F4-9 and phenylboric acid.

[2187] LCMS: m/z 487 [M+H].sup.+

[2188] HPLC retention time: 2.15 min (analysis condition U)

Example 335

Compound F5-40

8-(4-Cyclopropyl-piperazin-1-yl)-6,6-dimethyl-11-oxo-9-pyridin-3-yl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2189] ##STR00350##

[2190] Under the same conditions as the method for synthesizing Compound E4-7-1, the title compound was prepared from Compound F4-9 and pyridine-3-boric acid.

[2191] LCMS: m/z 488 [M+H].sup.+

[2192] HPLC retention time: 1.53 min (analysis condition U)

Example 336

Compound F5-41

8-(4-Cyclopropyl-piperazin-1-yl)-6,6-dimethyl-11-oxo-9-thiophene-2-yl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2193] ##STR00351##

[2194] Under the same conditions as the method for synthesizing Compound E4-7-1, the title compound was prepared from Compound F4-9 and thiophene-2-boric acid.

[2195] LCMS: m/z 493 [M+H].sup.+

[2196] HPLC retention time: 2.13 min (analysis condition U)

Example 337

Compound F5-42

8-(4-Cyclopropyl-piperazin-1-yl)-6,6,9-trimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2197] ##STR00352##

[2198] Under the same conditions as the method for synthesizing Compound F5-47, the title compound was prepared from Compound F4-9.

[2199] .sup.1H-NMR (270 MHz, DMSO-d.sub.6) : 12.71 (1H, br. s), 8.33-8.30 (1H, d, 8.08 Hz), 8.00 (1H, s), 7.96 (1H, s), 7.61-7.58 (1H, m), 7.29 (1H, s), 2.97 (4H, m), 2.73 (4H, m), 2.56 (1H, m), 2.34 (3H, s), 1.76 (6H, s), 1.64-1.58 (1H, m), 0.50-0.44 (2H, m), 0.37-0.32 (2H, m)

[2200] LCMS: m/z 425 [M+H].sup.+

Example 338

Compound F5-43

8-(4-Cyclobutyl-piperazin-1-yl)-9-ethynyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2201] ##STR00353##

[2202] Under nitrogen atmosphere, to the MeCN (8 ml) suspension of 9-bromo-8-(4-cyclobutyl-piperazin-1-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (Compound F4-10, 200 mg, 0.397 mmol), ethynyltriisopropylsilane (268 mg, 3.0 eq.), 2-dicyclohexylphosphino-2,4,6-triisopropylbiphenyl (Xphos) (39 mg, 0.2 eq.), Pd(CH.sub.3CN).sub.2Cl.sub.2 (11 mg, 0.1 eq.) and cesium carbonate (518 mg, 4.0 eq.) were added and the mixture was stirred and heated under reflux condition until the reaction is completed. Upon the completion of the reaction, distilled water was added to the reaction solution, which was then extracted with ethyl acetate. The organic layer was washed with brine and dried over sodium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/methanol) to obtain 8-(4-cyclobutyl-piperazin-1-yl)-6,6-dimethyl-11-oxo-9-[(triisopropylsilanyl)-ethynyl]-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (179 mg, 74%).

[2203] To the THF (6 ml) solution of the obtained compound (179 mg, 0.295 mmol), 1 M THF solution (710 l) of tetrabutylammonium fluoride was added and the mixture was stirred until the reaction is completed. Upon the completion of the reaction, ethyl acetate was added to the reaction solution, which was then washed with distilled water and dried over sodium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were washed with a mixture solvent of ethanol and distilled water to obtain the title compound (67 mg, 92%).

[2204] .sup.1H-NMR (400 MHz, DMSO-d.sub.6) : 12.85 (1H, s), 8.31 (1H, d, 7.9 Hz), 8.20 (1H, s), 8.03 (1H, s), 7.62 (1H, d, 7.9 Hz), 7.35 (1H, s), 4.62 (1H, s), 3.94-4.03 (2H, m), 3.79-3.89 (1H, m), 3.48-3.54 (2H, m), 3.27-3.38 (2H, m), 2.96-3.16 (2H, m), 2.30-2.41 (2H, m), 2.16-2.26 (2H, m), 1.72-1.85 (8H, m)

[2205] LCMS: m/z 449 [M+H].sup.+

[2206] HPLC retention time: 2.69 min (analysis condition W)

Example 339

Compound F5-44

8-(4-Cyclobutyl-piperazin-1-yl)-6,6-dimethyl-11-oxo-9-prop-1-ynyl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2207] ##STR00354##

[2208] Under the same conditions as the method for synthesizing Compound E4-2-1, the title compound was prepared from Compound F4-10 under propyne gas atmosphere.

[2209] .sup.1H-NMR (400 MHz, DMSO-d.sub.6) : 12.71 (1H, s), 8.30 (1H, d, 7.9 Hz), 8.06 (1H, s), 8.00 (1H, s), 7.59 (1H, d, 7.9 Hz), 7.20 (1H, s), 2.75-2.83 (1H, m), 2.40-2.48 (4H, m), 2.11 (3H, s), 1.97-2.06 (2H, m), 1.76 (6H, s), 1.62-1.71 (2H, m)

[2210] LCMS: m/z 463 [M+H].sup.+

[2211] HPLC retention time: 2.80 min (analysis condition W)

Example 340

Compound F5-45

9-Cyclobutylethynyl-8-(4-cyclobutyl-piperazin-1-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2212] ##STR00355##

[2213] Under the same conditions as the method for synthesizing Compound E4-2-1, the title compound was prepared from Compound F4-10 and ethynylcyclobutane.

[2214] LCMS: m/z 503 [M+H].sup.+

[2215] HPLC retention time: 1.85 min (analysis condition S)

Example 341

Compound F5-46

8-(4-Cyclobutyl-piperazin-1-yl)-9-cyclopropyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2216] ##STR00356##

[2217] Under the same conditions as the method for synthesizing Compound B3-32, the title compound was prepared from Compound F5-15-2 and cyclobutanone.

[2218] .sup.1H-NMR (400 MHz, DMSO-d.sub.6) : 8.23 (1H, d, 8 Hz), 7.92 (1H, br. s), 7.59 (1H, s), 7.47 (1H, br. d, 8 Hz), 7.28 (1H, s), 3.12 (4H, br. s), 2.80 (1H, dddd, 8, 8, 8, 8 Hz), 2.20-2.13 (1H, m), 2.01 (2H, br. s), 1.86-1.68 (10H, m), 1.05 (2H, d, 8 Hz), 0.76 (2H, d, 4 Hz)

[2219] LCMS: m/z 465 [M+H].sup.+

[2220] HPLC retention time: 2.79 min (analysis condition W)

[2221] Hydrochloric Acid Salt of Compound F5-46

[2222] 8-(4-Cyclobutyl-piperazin-1-yl)-9-cyclopropyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile was added with DMSO and 6 N hydrochloric acid (1.05 eq.) and dissolved therein. After freeze-drying, crystallization was performed by using ethanol comprising 25% water to obtain monohydrochloric acid salt of 8-(4-cyclobutyl-piperazin-1-yl)-9-cyclopropyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile.

[2223] .sup.1H-NMR (400 MHz, DMSO-d.sub.6) : 12.81 (1H, s), 10.64 (1H, br. s), 8.32-8.29 (1H, m), 8.01 (1H, s), 7.67 (1H, s), 7.61-7.60 (1H, m), 7.33 (1H, s), 4.00-3.39 (6H, m), 3.28-3.02 (3H, m), 2.45-2.05 (5H, m), 1.83-1.77 (8H, m), 1.09-1.07 (2H, m), 0.81-0.80 (2H, m)

[2224] LCMS: m/z 465 [M+H].sup.+

Example 342

Compound F5-47

8-(4-Cyclobutyl-piperazin-1-yl)-6,6,9-trimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2225] ##STR00357##

[2226] Under nitrogen atmosphere, to the N,N-dimethyl formamide (1.5 ml) solution of 9-bromo-8-(4-cyclobutyl-piperazin-1-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (Compound F4-10, 50 mg, 0.099 mmol), trimethyl boroxine (12 mg, 0.1 eq.), tetrakis triphenylphosphine palladium (39 mg, 0.2 eq.), and potassium carbonate (41 mg, 3.0 eq.) were added, and the mixture was stirred at 100 C. for 24 hr. Upon the completion of the reaction, distilled water was added to the reaction solution, which was then extracted with ethyl acetate. The organic layer was washed with brine and dried over sodium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/methanol) to obtain the title compound (25 mg, 58%).

[2227] .sup.1H-NMR (400 MHz, DMSO-d.sub.6) : 12.67 (1H, s), 8.31 (1H, d, 7.9 Hz), 7.98 (1H, s), 7.95 (1H, s), 7.59 (1H, d, 7.9 Hz), 7.30 (1H, s), 2.96-3.04 (4H, m), 2.76-2.84 (1H, m), 2.39-2.48 (4H, m), 2.32 (3H, s), 1.78-1.87 (2H, m), 1.75 (6H, s), 1.63-1.71 (2H, m)

[2228] LCMS: m/z 439 [M+H].sup.+

[2229] HPLC retention time: 2.66 min (analysis condition W)

Example 343

Compound F5-48

8-(4-Cyclobutyl-piperazin-1-yl)-9-isopropenyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2230] ##STR00358##

[2231] Under the same conditions as the method for synthesizing Compound E4-7-1, the title compound was prepared from Compound F4-10 and 2-isopropenyl-4,4,5,5-tetramethyl-[1,3,2] dioxaborolane.

[2232] LCMS: m/z 465 [M+H].sup.+

[2233] HPLC retention time: 1.63 min (analysis condition S)

Example 344

Compound F5-49

9-Ethynyl-6,6-dimethyl-8-(4-morpholin-4-yl-piperidin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2234] ##STR00359##

[2235] Under the same conditions as the method for synthesizing Compound F5-43, the title compound was prepared from Compound F3-11.

[2236] LCMS: m/z 479 [M+H].sup.+

[2237] HPLC retention time: 1.90 min (analysis condition U)

Example 345

Compound F5-50

6,6-Dimethyl-8-(4-morpholin-4-yl-piperidin-1-yl)-11-oxo-9-prop-1-ynyl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2238] ##STR00360##

[2239] Under the same conditions as the method for synthesizing Compound E4-2-1, the title compound was prepared from Compound F3-11 and propyne gas.

[2240] .sup.1H-NMR (270 MHz, CD.sub.3OD+CDCl.sub.3) : 8.40 (1H, d, J=7.8 Hz), 8.24 (1H, s), 7.84 (1H, s), 7.54 (1H, d, J=7.8 Hz), 7.14 (1H, s), 4.01-3.96 (2H, m), 3.78 (4H, m), 2.88-2.84 (2H, m), 2.68 (4H, m), 2.16-1.73 (5H, m), 2.16 (3H, s), 1.80 (6H, s)

[2241] LCMS: m/z 493 [M+H].sup.+

Example 346

Compound F5-51

6,6,9-Trimethyl-8-(4-morpholin-4-yl-piperidin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2242] ##STR00361##

[2243] Under the same conditions as the method for synthesizing Compound F5-47, the title compound was prepared from Compound F3-11

[2244] .sup.1H-NMR (270 MHz, DMSO-d.sub.6) : 12.70 (1H, br. s), 8.33-8.30 (1H, d, 8.08 Hz), 8.00 (1H, s), 7.95 (1H, s), 7.61-7.58 (1H, m), 7.28 (1H, s), 3.60 (4H, m), 3.32-3.26 (2H, m), 2.79-2.69 (2H, m), 2.32 (3H, s), 1.95-1.90 (2H, m), 1.74 (6H, s), 1.65-1.52 (2H, m),

[2245] LCMS: m/z 469 [M+H].sup.+

[2246] Methanesulfonic Acid Salt of Compound F5-51

[2247] 6,6,9-Trimethyl-8-(4-morpholin-4-yl-piperidin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile was added with DMSO and 2 N methanesulfonic acid (1.05 eq.) and dissolved therein. After freeze-drying, crystallization was performed with ethanol to obtain methanesulfonic acid salt of 6,6,9-trimethyl-8-(4-morpholin-4-yl-piperidin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile.

[2248] .sup.1H-NMR (270 MHz, DMSO-d.sub.6) : 12.72 (1H, br. s), 9.60 (1H, br. s), 8.33-8.31 (1H, d, 9.8 Hz), 8.01 (1H, s), 7.99 (1H, s), 7.61-7.59 (1H, m), 7.31 (1H, s), 4.07-4.04 (2H, m), 3.73-3.67 (2H, m), 3.55-3.40 (8H, m), 3.32-3.26 (1H, m), 2.70-2.60 (2H, m), 2.34 (3H, s), 2.30 (3H, s), 1.95-1.90 (2H, m), 1.75 (6H, s)

[2249] LCMS: m/z 469 [M+H].sup.+

Example 347

Compound F6-1

9-(1-Isopropyl-1,2,3,6-tetrahydro-pyridin-4-yl)-6,6-dimethyl-11-oxo-8-(4-pyrrolidin-1-yl-piperidin-1-yl)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2250] ##STR00362##

[2251] Under the same conditions as the method for synthesizing Compound B3-32, the title compound was prepared from Compound F5-36-2 and acetone.

[2252] .sup.1H-NMR (400 MHz, DMSO-d.sub.6) : 12.68 (1H, br. s), 8.30 (1H, d, 8.1 Hz), 7.98 (1H, s), 7.82 (1H, s), 7.58 (1H, d, 8.1 Hz), 7.20 (1H, s), 5.85 (1H, s), 3.56-3.44 (2H, m), 3.21-3.14 (2H, m), 2.77-2.66 (5H, m), 2.12-2.09 (1H, m), 1.98-1.88 (2H, m), 1.74 (6H, s), 1.70-1.63 (1H, m), 1.58-1.45 (2H, m), 1.09-1.00 (6H, m)

[2253] LCMS: m/z 563 [M+H].sup.+

[2254] HPLC retention time: 1.90 min (analysis condition U)

Example 348

Compound F6-2

9-(1-Methanesulfonyl-1,2,3,6-tetrahydro-pyridin-4-yl)-6,6-dimethyl-11-oxo-8-(4-pyrrolidin-1-yl-piperidin-1-yl)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2255] ##STR00363##

[2256] Under the same conditions as the method for synthesizing Compound A9-1, the title compound was prepared from Compound F5-36-2.

[2257] LCMS: m/z 598 [M+H].sup.+

[2258] HPLC retention time: 1.52 min (analysis condition S)

Example 349

Compound F6-3

9-[3-(4-Cyclopropyl-piperazin-1-yl)-propyl]-6,6-dimethyl-8-morpholin-4-yl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2259] ##STR00364##

[2260] Under the same conditions as the method for synthesizing Compound B3-13-1, the title compound was prepared from Compound F5-10.

[2261] LCMS: m/z 538 [M+H].sup.+

[2262] HPLC retention time: 1.32 min (analysis condition S)

Example 350

Compound F6-4

9-Ethyl-6,6-dimethyl-8-(4-oxetan-3-yl-piperazin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2263] ##STR00365##

[2264] Under the same conditions as the method for synthesizing Compound B3-13-1, the title compound was prepared from Compound F5-16.

[2265] .sup.1H-NMR (400 MHz, DMSO-d.sub.6) : 12.70 (1H, br. s), 8.29 (1H, d, 8.0 Hz), 8.03-7.94 (2H, m), 7.59-7.55 (1H, m), 7.38 (1H, s), 4.59-4.47 (4H, m), 3.53-5.47 (1H, m), 3.03-2.97 (2H, m), 2.73-2.62 (2H, m), 1.74 (6H, s), 1.29-1.98 (3H, m)

[2266] LCMS: m/z 455 [M+H].sup.+

[2267] HPLC retention time: 1.92 min (analysis condition U)

[2268] Hydrochloric Acid Salt of Compound F6-4

[2269] 9-Ethyl-6,6-dimethyl-8-(4-oxetan-3-yl-piperazin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile was added with DMSO and 6 N hydrochloric acid (1.05 eq.) and dissolved therein. After freeze-drying, crystallization was performed with ethanol comprising 25% water to obtain monohydrochloric acid salt of 9-ethyl-6,6-dimethyl-8-(4-oxetan-3-yl-piperazin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile.

[2270] .sup.1H-NMR (270 MHz, DMSO-d.sub.6) : 12.83 (1H, br. s), 11.59 (1H, br. s), 8.33-8.31 (1H, m), 8.09 (1H, s), 8.02 (1H, s), 7.63-7.61 (1H, m), 7.39 (1H, s), 4.91-4.60 (4H, br. m), 3.58-3.40 (1H, m), 3.31-3.05 (8H, br. m), 2.73 (2H, q, J=7.3), 1.81 (6H, s), 1.29 (3H, t, J=7.3)

[2271] LCMS: m/z 455 [M+H].sup.+

Example 351

Compound F6-5

9-(3-Methoxy-propyl)-6,6-dimethyl-8-(4-oxetan-3-yl-piperazin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2272] ##STR00366##

[2273] Under the same conditions as the method for synthesizing Compound B3-13-1, the title compound was prepared from Compound F5-18.

[2274] .sup.1H-NMR (270 MHz, DMSO-d.sub.6) : 12.73 (1H, br. s), 8.33-8.30 (1H, d, 8.08 Hz), 8.01 (1H, s), 8.00 (1H, s), 7.62-7.59 (1H, d, 8.08 Hz), 7.42 (1H, s), 4.61-4.56 (2H, m), 4.51-4.46 (2H, m), 3.53-3.47 (1H, m), 3.42-3.37 (2H, m), 3.02 (4H, m), 2.75-2.68 (2H, m), 2.51 (4H, m), 1.93-1.82 (2H, m), 1.76 (6H, s)

[2275] LCMS: m/z 499 [M+H].sup.+

Example 352

Compound F6-6

6,6-Dimethyl-8-(4-oxetan-3-yl-piperazin-1-yl)-9-[3-(4-oxetan-3-yl-piperazin-1-yl)-propyl]-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2276] ##STR00367##

[2277] Under the same conditions as the method for synthesizing Compound B3-13-1, the title compound was prepared from Compound F5-20.

[2278] LCMS: m/z 609 [M+H].sup.+

[2279] HPLC retention time: 1.00 min (analysis condition S)

Example 353

Compound F6-7

9-(2-Cyclopentyl-ethyl)-6,6-dimethyl-8-(4-oxetan-3-yl-piperazin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2280] ##STR00368##

[2281] Under the same conditions as the method for synthesizing Compound B3-13-1, the title compound was prepared from Compound F5-21.

[2282] LCMS: m/z 523 [M+H].sup.+

[2283] HPLC retention time: 1.92 min (analysis condition S)

Example 354

Compound F6-8

6,6-Dimethyl-8-(4-oxetan-3-yl-piperazin-1-yl)-11-oxo-9-propyl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2284] ##STR00369##

[2285] Under the same conditions as the method for synthesizing Compound B3-13-1, the title compound was prepared from Compound F5-22.

[2286] .sup.1H-NMR (270 mHz DMSO-d.sub.6) : 12.75 (1H, s), 8.30 (1H, d, J=8.2 Hz), 8.01-7.97 (2H, m), 7.59 (1H, d, J=7.1 Hz), 7.38 (1H, s), 4.51 (4H, dt, J=27.7, 6.3 Hz), 3.55-3.49 (1H, m), 3.02-2.96 (4H, m), 2.63 (2H, t, J=7.3 Hz), 2.47-2.41 (4H, m), 1.73 (6H, s), 1.70-1.61 (2H, m), 0.94 (3H, t, J=7.4 Hz).

[2287] LCMS: m/z 469 [M+H].sup.+

[2288] HPLC retention time: 1.57 min (analysis condition S)

Example 355

Compound F6-9

8-[4-(4-Hydroxy-butyl)-piperazin-1-yl]-6,6-dimethyl-11-oxo-9-propyl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2289] ##STR00370##

[2290] The title compound was obtained as a by-product of the synthesis of Compound F6-8.

[2291] LCMS: m/z 485 [M+H].sup.+

[2292] HPLC retention time: 1.61 min (analysis condition S)

Example 356

Compound F6-10

9-(3-Hydroxy-propyl)-6,6-dimethyl-8-(4-oxetan-3-yl-piperazin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2293] ##STR00371##

[2294] Under the same conditions as the method for synthesizing Compound B3-13-1, the title compound was prepared from Compound F5-23.

[2295] LCMS: m/z 499 [M+H].sup.+

[2296] HPLC retention time: 1.42 min (analysis condition S)

Example 357

Compound F6-11

6,6-Dimethyl-9-(3-morpholin-4-yl-propyl)-8-(4-oxetan-3-yl-piperazin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2297] ##STR00372##

[2298] Under the same conditions as the method for synthesizing Compound B3-13-1, the title compound was prepared from Compound F5-26.

[2299] LCMS: m/z 554 [M+H].sup.+

[2300] HPLC retention time: 1.50 min (analysis condition U)

Example 358

Compound F6-12

6,6-Dimethyl-8-(4-oxetan-3-yl-piperazin-1-yl)-11-oxo-9-pentyl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2301] ##STR00373##

[2302] Under the same conditions as the method for synthesizing Compound B3-13-1, the title compound was prepared from Compound F5-27.

[2303] LCMS: m/z 497 [M+H].sup.+

[2304] HPLC retention time: 2.25 min (analysis condition U)

Example 359

Compound F6-13

9-(3-Isopropoxy-prop-1-ynyl)-6,6-dimethyl-8-(4-oxetan-3-yl-piperazin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2305] ##STR00374##

[2306] Under the same conditions as the method for synthesizing Compound A7-17, the title compound was prepared from Compound F5-23 and 2-bromopropane.

[2307] .sup.1H-NMR (270 MHz, CD.sub.3OD+CDCl.sub.3) : 8.40 (1H, d, J=7.8 Hz), 8.32 (1H, s), 7.84 (1H, s), 7.53 (1H, d, J=7.8 Hz), 7.18 (1H, s), 4.80-4.68 (4H, m), 4.46 (2H, s), 3.95 (1H, m), 3.64 (1H, m), 3.46 (4H, m), 2.62 (4H, m), 1.82 (6H, s), 1.24 (6H, d, J=7.0 Hz)

[2308] LCMS: m/z 523 [M+H].sup.+

Example 360

Compound F6-14

9-Isopropyl-6,6-dimethyl-8-(4-oxetan-3-yl-piperazin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2309] ##STR00375##

[2310] Under the same conditions as the method for synthesizing Compound B3-13-1, the title compound was prepared from Compound F5-32.

[2311] .sup.1H-NMR (270 MHz, CD.sub.3OD+CDCl.sub.3) : 8.44 (1H, d, J=7.8 Hz), 8.27 (1H, s), 7.84 (1H, s), 7.54 (1H, d, J=7.8 Hz), 7.36 (1H, s), 4.82-4.70 (4H, m), 3.68 (1H, m), 3.45 (1H, m), 3.13-3.09 (4H, m), 2.64-2.62 (4H, m), 1.81 (6H, s), 1.31 (6H, d, J=7.0 Hz)

[2312] LCMS: m/z 469 [M+H].sup.+

Example 361

Compound F6-15

8-(4-Cyclopropyl-piperazin-1-yl)-9-ethyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2313] ##STR00376##

[2314] Under the same conditions as the method for synthesizing Compound B3-13-1, the title compound was prepared from Compound F5-37.

[2315] LCMS: m/z 439 [M+H].sup.+

[2316] HPLC retention time: 1.98 min (analysis condition U)

Example 362

Compound F6-16

8-(4-Cyclopropyl-piperazin-1-yl)-6,6-dimethyl-11-oxo-9-propyl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2317] ##STR00377##

[2318] Under the same conditions as the method for synthesizing Compound B3-13-1, the title compound was prepared from Compound F5-38.

[2319] LCMS: m/z 453 [M+H].sup.+

[2320] HPLC retention time: 1.63 min (analysis condition S)

Example 363

Compound F6-17

8-(4-Cyclobutyl-piperazin-1-yl)-9-ethyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2321] ##STR00378##

[2322] Under the same conditions as the method for synthesizing Compound B3-13-1, the title compound was prepared from Compound F5-43.

[2323] .sup.1H-NMR (400 MHz, DMSO-d.sub.6) : 12.80 (1H, s), 8.32 (1H, d, 7.9 Hz), 8.10 (1H, s), 8.02 (1H, s), 7.62 (1H, d, 7.9 Hz), 7.38 (1H, s), 3.78-3.88 (1H, m), 3.79-3.89 (1H, m), 3.48-3.54 (2H, m), 3.40- 3.47 (2H, m), 3.30-3.39 (2H, m), 3.02-3.24 (4H, m), 2.73 (2H, q, 7.3 Hz), 2.30-2.41 (2H, m), 2.17-2.26 (2H, m), 1.71-1.86 (8H, m), 1.29 (3H, t, 7.3 Hz)

[2324] LCMS: m/z 453 [M+H].sup.+

[2325] HPLC retention time: 2.76 min (analysis condition W)

[2326] Methanesulfonic Acid Salt of Compound F6-17

[2327] 8-(4-Cyclobutyl-piperazin-1-yl)-9-ethyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile was dissolved in 6 volumes of DMF at room temperature and added dropwise with aqueous solution of methanesulfonic acid (2 M, 1.05 eq.). The resulting solution was added dropwise to 60 volumes of acetonitrile, and the precipitated solid was filtered and dried to obtain monomethanesulfonic acid salt of 8-(4-cyclobutyl-piperazin-1-yl)-9-ethyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile.

[2328] .sup.1H-NMR (400 MHz, DMSO-d.sub.6) : 12.75 (1H, s), 8.31 (1H, J=8.4 Hz), 8.07 (1H, s), 8.01 (1H, s), 7.59 (1H, d, J=7.9 Hz), 7.38 (1H, s), 3.58-2.84 (10H, m), 2.71 (2H, q, J=7.5 Hz), 2.34 (3H, s), 2.20-2.04 (4H, m), 1.76-1.68 (8H, m), 1.26 (3H, t, J=7.5 Hz) FABMS: m/z 453 [M+H].sup.+

Example 364

Compound F6-18

8-(4-Cyclobutyl-piperazin-1-yl)-6,6-dimethyl-11-oxo-9-propyl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2329] ##STR00379##

[2330] Under the same conditions as the method for synthesizing Compound B3-13-1, the title compound was prepared from Compound F5-44.

[2331] .sup.1H-NMR (400 MHz, DMSO-d.sub.6) : 12.69 (1H, s), 8.31 (1H, d, 7.9 Hz), 8.01 (1H, s), 7.99 (1H, s), 7.60 (1H, d, 7.9 Hz), 7.39 (1H, s), 2.92-3.02 (4H, m), 2.75-2.84 (1H, m), 2.65 (2H, t, 7.3 Hz), 2.38-2.48 (4H, m), 1.96-2.06 (2H, m), 1.78-1.87 (2H, m), 1.75 (6H, s), 1.62-1.73 (4H, m), 0.97 (3H, t, 7.3 Hz)

[2332] LCMS: m/z 467 [M+H].sup.+

[2333] HPLC retention time: 2.96 min (analysis condition W)

Example 365

Compound F6-19

8-(4-Cyclobutyl-piperazin-1-yl)-9-isopropyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2334] ##STR00380##

[2335] Under the same conditions as the method for synthesizing Compound B3-13, the title compound was prepared from Compound F5-48.

[2336] LCMS: m/z 467 [M+H].sup.+

[2337] HPLC retention time: 1.67 min (analysis condition S)

Example 366

Compound F6-20

9-Ethyl-6,6-dimethyl-8-(4-morpholin-4-yl-piperidin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2338] ##STR00381##

[2339] Under the same conditions as the method for synthesizing Compound B3-13-1, the title compound was prepared from Compound F5-49.

[2340] .sup.1H-NMR (400 MHz, DMSO-d.sub.6) : 12.70 (1H, s), 8.32 (1H, d, J=7.9 Hz), 8.04 (1H, s), 8.00 (1H, s), 7.61 (1H, d, J=8.5 Hz), 7.34 (1H, s), 3.64-3.57 (4H, m), 3.27-3.18 (2H, m), 2.82-2.66 (4H, m), 2.39-2.28 (1H, m), 1.96-1.87 (2H, m), 1.76 (6H, s), 1.69-1.53 (2H, m), 1.29 (3H, t, J=7.3 Hz)

[2341] LCMS: m/z 483 [M+H].sup.+

[2342] HPLC retention time: 1.98 min (analysis condition U)

[2343] Hydrochloric Acid Salt of Compound F6-20

[2344] 9-Ethyl-6,6-dimethyl-8-(4-morpholin-4-yl-piperidin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile was dissolved in a mixture solution of methylethyl ketone (10 volumes), water (4 volumes) and acetic acid (3 volumes) at 60 C. To the dissolved solution, hydrochloric acid (2 N) was added dropwise (1 volume). After stirring at 60 C. for 30 min, ethanol (25 volume) was added dropwise. The precipitated solid was filtered and dried to obtain monohydrochloric acid salt of 9-ethyl-6,6-dimethyl-8-(4-morpholin-4-yl-piperidin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile.

[2345] .sup.1H-NMR (400 MHz, DMSO-d.sub.6) : 12.78 (1H, s), 10.57 (1H, br. s), 8.30 (1H, J=8.4 Hz), 8.05 (1H, s), 7.99 (1H, s), 7.59 (1H, d, J=7.9 Hz), 7.36 (1H, s), 4.02-3.99 (2H, m), 3.84-3.78 (2H, m), 3.51-3.48 (2H, m), 3.15-3.13 (1H, s), 2.83-2.73 (2H, s), 2.71-2.67 (2H, s), 2.23-2.20 (2H, m), 1.94-1.83 (2H, m), 1.75 (6H, s), 1.27 (3H, t, J=7.5 Hz)

[2346] FABMS: m/z 483 [M+H].sup.+

Example 367

Compound F6-21

6,6-Dimethyl-8-(4-morpholin-4-yl-piperidin-1-yl)-11-oxo-9-propyl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2347] ##STR00382##

[2348] Under the same conditions as the method for synthesizing Compound B3-13-1, the title compound was prepared from Compound F5-50.

[2349] .sup.1H-NMR (270 MHz, CD.sub.3OD+CDCl.sub.3) : 8.41 (1H, d, J=7.8 Hz), 8.14 (1H, s), 7.84 (1H, s), 7.53 (1H, d, J=7.8 Hz), 7.31 (1H, s), 3.77 (4H, m), 3.32 (2H, m), 2.86-2.66 (8H, m), 2.43-2.05 (3H, m), 1.79 (6H, s), 1.79-1.66 (4H, m), 1.02 (3H, t, J=7.3 Hz)

[2350] LCMS: m/z 497 [M+H].sup.+

Example 368

Compound G2

8-Methoxy-10,10-dimethyl-10,11-dihydro-5H-1,11-diaza-benzo[B]fluorene

[2351] ##STR00383##

[2352] 2-Hydrazinopyridine (1.3 g, 11.8 mmol) and 7-methoxy-1,1-dimethyl-3,4-dihydro-1H-naphthalen-2-one (Compound A2, 2.4 g, 11.8 mmol) were dissolved in NMP (60 mL), and stirred at 190 C. for 48 hr. The reaction solution was diluted with ethyl acetate, washed with water and dried over magnesium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (hexane/ethyl acetate) to obtain the target compound (white solid, 101 mg, 3%).

[2353] .sup.1H-NMR (400 MHz, DMSO-d.sub.6) : 11.53 (1H, s), 8.16-8.12 (1H, m), 7.84 (1H, d, J=7.8 Hz), 7.23 (1H, d, J=8.4 Hz), 7.11 (1H, s), 7.03-6.98 (1H, m), 6.85-6.81 (1H, m), 3.96 (2H, s), 3.77 (3H, s), 1.64 (6H, s)

[2354] LCMS: m/z 279 [M+H].sup.+

[2355] HPLC retention time: 2.08 min (analysis condition U)

Example 369

Compound G3

8-Methoxy-10,10-dimethyl-10,11-dihydro-1,11-diaza-benzo[b]fluoren-5-one

[2356] ##STR00384##

[2357] Under the same conditions as the method for synthesizing Compound A4, the title compound was prepared from Compound G2.

[2358] .sup.1H-NMR (400 MHz, CDCl.sub.3) : 12.95 (1H, br. s), 8.78 (1H, d, J=7.8 Hz), 8.52 (1H, d, J=4.9 Hz), 8.41 (1H, d, J=8.8 Hz), 7.37 (1H, dd, J=7.7, 5.0 Hz), 7.15 (1H, s), 7.04-7.00 (1H, m), 3.94 (3H, s), 1.98 (6H, s)

[2359] LCMS: m/z 293 [M+H].sup.+

[2360] HPLC retention time: 2.13 min (analysis condition U)

Example 370

Compound G4

8-Hydroxy-10,10-dimethyl-10,11-dihydro-1,11-diaza-benzo[b]fluoren-5-one

[2361] ##STR00385##

[2362] Under the same conditions as the method for synthesizing Compound E3-2, the title compound was prepared from Compound G3.

[2363] .sup.1H-NMR (400 MHz, CDCl.sub.3) : 8.66 (1H, d, J=7.7 Hz), 8.29 (1H, d, J=4.9 Hz), 8.23 (1H, d, J=13.8 Hz), 7.29 (1H, dd, J=7.7, 5.0 Hz), 7.12 (1H, s), 6.93 (1H, d, J=8.6 Hz), 1.71 (6H, s)

[2364] LCMS: m/z 279 [M+H].sup.+

[2365] HPLC retention time: 1.72 min (analysis condition U)

Example 371

Compound G5

Trifluoro-methanesulfonic Acid 10,10-dimethyl-5-oxo-10,11-dihydro-5H-1,11-diaza-benzo[b]fluoren-8-yl ester

[2366] ##STR00386##

[2367] Under the same conditions as the method for synthesizing Compound B1, the title compound was prepared from Compound G4.

[2368] .sup.1H-NMR (400 MHz, CDCl.sub.3) : 8.81 (1H, d, J=7.8 Hz), 8.60-8.52 (2H, m), 7.55 (1H, s), 7.46-7.40 (2H, m), 2.01 (6H, s)

[2369] LCMS: m/z 411 [M+H].sup.+

[2370] HPLC retention time: 1.75 min (analysis condition U)

Example 372

Compound G6

10,10-Dimethyl-8-(4-pyrrolidin-1-yl-piperidin-1-yl)-10,11-dihydro-1,11-diaza-benzo[b]fluoren-5-one

[2371] ##STR00387##

[2372] Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound G5 and 4-pyrrolidin-1-yl-piperidine.

[2373] .sup.1H-NMR (400 MHz, CDCl.sub.3) : 13.12 (1H, s), 8.78 (1H, d, J=7.8 Hz), 8.49 (1H, d, J=4.9 Hz), 8.29 (1H, d, J=8.8 Hz), 7.34 (1H, dd, J=7.7, 5.0 Hz), 7.06-6.98 (2H, m), 3.96-3.88 (2H, m), 3.02-3.92 (2H, m), 2.69-2.60 (4H, m), 2.32-2.23 (1H, m), 2.09-2.00 (4H, m), 1.92 (6H, s), 1.26-1.19 (4H, m)

[2374] LCMS: m/z 415 [M+H].sup.+

[2375] HPLC retention time: 1.57 min (analysis condition U)

Example 373

Compound H1

6-Acetyl-7-methoxy-1,1-dimethyl-3,4-dihydro-1H-naphthalen-2-one

[2376] ##STR00388##

[2377] To the dichloromethane (70 ml) solution of 7-methoxy-1,1-dimethyl-3,4-dihydro-1H-naphthalen-2-one (Compound A2, 3 g, 14.7 mmol), acetic anhydride (1.7 ml, 1.2 eq.) and aluminum chloride-nitrobenzene solution (1 M, 44 ml, 3 eq.) was added at 0 C., and stirred for 3 hr. Thereafter, the reaction solution was added with saturated aqueous solution of sodium hydrogen carbonate and extracted twice with dichloromethane. The organic layer was washed with brine and dried over magnesium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain the title compound as a crude product.

Example 374

Compound H2-1

1-(3-Bromo-8-methoxy-6,6-dimethyl-6,11-dihydro-5H-benzo[b]carbazol-9-yl)-ethanone

[2378] ##STR00389##

[2379] Under the same conditions as the method for synthesizing Compound A3-1, the title compound was prepared from Compound H1 and (3-bromo-phenyl)-hydrazine.

[2380] LCMS: m/z 398 [M+H].sup.+

[2381] HPLC retention time: 3.97 min (analysis condition Y)

Example 375

Compound H2-2

1-(1-Bromo-8-methoxy-6,6-dimethyl-6,11-dihydro-5H-benzo[b]carbazol-9-yl)-ethanone

[2382] ##STR00390##

[2383] The title compound was obtained as a by-product of the synthesis of Compound H2-1.

[2384] LCMS: m/z 398 [M+H].sup.+

[2385] HPLC retention time: 3.97 min (analysis condition Y)

Example 376

Compound H3

9-Acetyl-3-bromo-8-methoxy-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one

[2386] ##STR00391##

[2387] Under the same conditions as the method for synthesizing Compound A4, the title compound was prepared from Compound H2.

[2388] .sup.1H-NMR (300 MHz, DMSO-d.sub.6) : 1.80 (6H, s), 2.58 (3H, s), 4.06 (3H, s), 7.38 (1H, dd, 8.39 Hz, 1.91 Hz), 7.51 (1H, s), 7.67 (1H, bs, 1.53 Hz), 8.10 (1H, d, 8.39 Hz), 8.41 (1H, s), 12.3 (1H, s)

[2389] LCMS: m/z 412, 414 [M+H].sup.+

[2390] HPLC retention time: 2.73 min (analysis condition U)

Example 377

Compound H4

9-Acetyl-8-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2391] ##STR00392##

[2392] According to the same method as the method for synthesizing Compound A5-2, the title compound was prepared from Compound H3.

[2393] .sup.1H-NMR (300 MHz, DMSO-d.sub.6) : 1.83 (6H, s), 2.58 (3H, s), 4.07 (3H, s), 7.53 (1H, s), 7.61 (1H, d, 8.01 Hz), 8.03 (1H, s), 8.31 (1H, d, 8.77 Hz), 8.42 (1H, s), 12.8 (1H, s).

[2394] LCMS: m/z 359 [M+H].sup.+

[2395] HPLC retention time: 2.47 min (analysis condition U)

Example 378

Compound H5

9-Acetyl-8-hydroxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2396] ##STR00393##

[2397] Under the same conditions as the method for synthesizing Compound A6, the title compound was prepared from Compound H4.

[2398] .sup.1H-NMR (300 MHz, DMSO-d.sub.6) : 1.77 (6H, s), 2.75 (3H, s), 7.43 (1H, s), 7.63 (1H, d, 8.01 Hz), 8.02 (1H, s), 8.32 (1H, d, 8.01 Hz), 8.67 (1H, s), 12.2 (1H, s), 12.8 (1H, s).

[2399] LCMS: m/z 345 [M+H].sup.+

[2400] HPLC retention time: 2.27 min (analysis condition S)

Example 379

Compound H6-1

9-Acetyl-6,6-dimethyl-11-oxo-8-(tetrahydro-pyran-4-yl oxy)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2401] ##STR00394##

[2402] Under the same conditions as the method for synthesizing Compound A7-1, the title compound was prepared from Compound H5 and tetrahydropyran-4-ol.

[2403] LCMS: m/z 429 [M+H].sup.+

[2404] HPLC retention time: 2.48 min (analysis condition U)

Example 380

Compound H6-2

9-Acetyl-8-(2-diethylamino-ethoxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2405] ##STR00395##

[2406] Under the same conditions as the method for synthesizing Compound A7-17, the title compound was prepared from Compound H5.

[2407] LCMS: m/z 444 [M+H].sup.+

[2408] HPLC retention time: 2.05 min (analysis condition U)

Example 381

Compound H7

Trifluoro-methanesulfonic Acid 9-acetyl-3-cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl ester

[2409] ##STR00396##

[2410] Under the same conditions as the method for synthesizing Compound B1, the title compound was prepared from Compound H5.

[2411] .sup.1H-NMR (300 MHz, DMSO-d.sub.6) : 1.83 (6H, s), 2.74 (3H, s), 7.68 (1H, dd, 8.01 Hz, 1.53 Hz), 8.08 (2H, s), 8.33 (1H, d, 8.77 Hz), 8.79 (1H, s), 12.9 (1H, s).

Example 382

Compound H8-1

9-Acetyl-6,6-dimethyl-11-oxo-8-(4-pyrrolidin-1-yl-piperidin-1-yl)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2412] ##STR00397##

[2413] Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound H7 and 4-pyrrolidin-1-yl-piperidine.

[2414] .sup.1H-NMR (300 MHz, DMSO-d.sub.6) : 1.65 (2H, m), 1.69 (4H, s), 1.79 (6H, s), 1.95 (2H, m), 2.18 (1H, m), 2.54 (4H, s), 2.59 (3H, s), 2.93 (2H, t, 11.8 Hz), 3.37 (2H, m), 7.36 (1H, s), 7.60 (1H, d, 8.01), 8.01 (1H, s), 8.13 (1H, s), 8.30 (1H, d, 8.39), 12.7 (1H, s).

[2415] LCMS: m/z 481 [M+H].sup.+

[2416] HPLC retention time: 2.03 min (analysis condition U)

Example 383

Compound H8-2

9-Acetyl-8-(4-isopropyl-piperazin-1-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2417] ##STR00398##

[2418] Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound H7.

[2419] LCMS: m/z 455 [M+H].sup.+

[2420] HPLC retention time: 2.02 min (analysis condition U)

Example 384

Compound H8-3

9-Acetyl-6,6-dimethyl-8-morpholin-4-yl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2421] ##STR00399##

[2422] Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound H7 and morpholine.

[2423] LCMS: m/z 414 [M+H].sup.+

[2424] HPLC retention time: 2.11 min (analysis condition S)

Example 385

Compound H8-4

9-Acetyl-6,6-dimethyl-8-(4-morpholin-4-yl-piperidin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2425] ##STR00400##

[2426] Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound H7 and 4-piperidin-4-yl-morpholine.

[2427] LCMS: m/z 497 [M+H].sup.+

[2428] HPLC retention time: 1.45 min (analysis condition S)

Example 386

Compound H8-5

9-Acetyl-6,6-dimethyl-11-oxo-8-piperazin-1-yl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2429] ##STR00401##

[2430] Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound H7 and piperazine.

[2431] LCMS: m/z 413 [M+H].sup.+

[2432] HPLC retention time: 1.71 min (analysis condition U)

Example 387

Compound H9-1

9-Acetyl-8-(4-cyclobutyl-piperazin-1-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2433] ##STR00402##

[2434] Under the same conditions as the method for synthesizing Compound B3-32, the title compound was prepared from Compound H8-5 and cyclobutanone.

[2435] LCMS: m/z 467 [M+H].sup.+

[2436] HPLC retention time: 1.82 min (analysis condition U)

Example 388

Compound H9-2

9-Acetyl-6,6-dimethyl-11-oxo-8-[4-(tetrahydro-pyran-4-yl)-piperazin-1-yl]-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2437] ##STR00403##

[2438] Under the same conditions as the method for synthesizing Compound B3-32, the title compound was prepared from Compound H8-5 and tetrahydropyran-4-one.

[2439] LCMS: m/z 497 [M+H].sup.+

[2440] HPLC retention time: 1.76 min (analysis condition U)

Example 389

Compound H9-3

9-Acetyl-8-[4-(1,1-dimethyl-prop-2-ynyl)-piperazin-1-yl]-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2441] ##STR00404##

[2442] To the anhydrous THF solution (0.5 mL) of 9-acetyl-6,6-dimethyl-11-oxo-8-piperazin-1-yl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (Compound H8-5, 25 mg, 0.06 mmol), 3-chloro-3-methyl-but-1-yne (0.013 mL, 0.12 mmol), copper (I) chloride (0.6 mg, 0.006 mmol) and triethylamine (0.017 mL, 0.12 mmol) were added at room temperature. After stirring for 30 min, the mixture was added with water and extracted with ethyl acetate. The organic layer was dried over magnesium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were purified by amino silica gel column chromatography (dichloromethane/methanol) to obtain the title compound (white solid, 9.8 mg, 35%).

[2443] LCMS: m/z 479 [M+H].sup.+

[2444] HPLC retention time: 1.88 min (analysis condition U)

Example 390

Compound I1-1

6-Chloro-7-methoxy-1,1-dimethyl-3,4-dihydro-1H-naphthalen-2-one

[2445] ##STR00405##

[2446] 7-Methoxy-1,1-dimethyl-3,4-dihydro-1H-naphthalen-2-one (Compound A2, 3.37 g, 16.5 mmol) was dissolved in CH.sub.3CN (82 mL), added with NCS (2.42 g, 1.1 eq.) and stirred at 90 C. for 1.5 hr. The reaction solution was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over sodium sulfate. The drying agent was removed and the target compound was obtained after concentration under reduced pressure (yellow oily substance, 4.45 g).

[2447] .sup.1H-NMR (400 MHz, CDCl.sub.3) : 7.16 (1H, s), 6.85 (1H, s), 3.90 (3H, s), 3.00 (2H, t, J=6.8 Hz), 2.65 (2H, t, J=6.8 Hz), 1.42 (6H, s).

[2448] LCMS: m/z 239 [M+H].sup.+

[2449] HPLC retention time: 2.80 min (analysis condition U)

Example 391

Compound I1-2

9-Chloro-8-methoxy-6,6-dimethyl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2450] ##STR00406##

[2451] 6-Chloro-7-methoxy-1,1-dimethyl-3,4-dihydro-1H-naphthalen-2-one (Compound 11-1, 4.45 g, 16.5 mmol) and 3-hydrazinobenzonitrile (2.63 g, 1.2 eq.) were dissolved in TFA (91 mL), and stirred at 90 C. for 3 hr. According to the concentration under reduced pressure, TFA was removed and the residues were added with saturated aqueous solution of NaHCO.sub.3, followed by extraction with ethyl acetate. The organic layer was washed with saturated brine and dried over sodium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were added with ethyl acetate. After stirring at room temperature, the precipitated solid was separated by filtration. The filtrate was concentrated under reduced pressure to obtain the title compound as a mixture with 11-3 (red powder, 6.46 g).

Example 392

Compound I1-3

9-Chloro-8-methoxy-6,6-dimethyl-6,11-dihydro-5H-benzo[b]carbazole-1-carbonitrile

[2452] ##STR00407##

[2453] The title compound was obtained as a by-product of the synthesis of Compound I1-2.

[2454] .sup.1H-NMR (400 MHz, DMSO-d.sub.6) : 11.66 (1H, s), 7.65-7.69 (1H, m), 7.44-7.48 (1H, m), 7.39 (1H, s), 7.29 (1H, s), 7.17-7.23 (1H, m), 4.21 (2H, s), 3.91 (3H, s), 1.69 (6H, s).

[2455] LCMS: m/z 337 [M+H].sup.+

[2456] HPLC retention time: 3.15 min (analysis condition U)

Example 393

Compound I2-1

2-(4-Chloro-3-methoxy-phenyl)-2-methyl-propionitrile

[2457] ##STR00408##

[2458] 1-Chloro-4-fluoro-2-methoxy-benzene (4.3 g, 26.78 mmol) and isobutyronitrile (9.61 mL, 4.0 eq.) were dissolved in toluene (9.0 mL), added with KHMDS (80 mL, 0.5 M toluene solution) and stirred at 65 C. for 2 hr. The reaction solution was cooled to room temperature, added with aqueous solution of 1 N hydrochloric acid and then extracted with MTBE. The organic layer was washed with saturated brine and dried over magnesium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (hexane/ethyl acetate) to obtain the title compound (1.72 g, 31%).

[2459] .sup.1H-NMR (270 MHz, CDCl.sub.3) : 7.37 (1H, d, J=8.4 Hz), 7.05 (1H, d, J=2.1 Hz), 6.97 (1H, dd, J=8.2, 2.1 Hz), 3.95 (3H, s), 1.73 (6H, s).

[2460] HPLC retention time: 2.33 min (analysis condition S)

Example 394

Compound I2-2

4-(4-Chloro-3-methoxy-phenyl)-4-methyl-3-oxo-pentanoic acid ethyl ester

[2461] ##STR00409##

[2462] Under the same conditions as the method for synthesizing Compound K3, the title compound was prepared from Compound I2-1.

[2463] .sup.1H-NMR (270 MHz, DMSO-d.sub.6) : 7.42 (1H, d, J=8.1 Hz), 6.92 (1H, d, J=2.1 Hz), 6.86 (1H, dd, J=8.2, 2.3 Hz), 4.01 (2H, q, J=7.1 Hz), 3.87 (3H, s), 3.43 (2H, s), 1.44 (6H, s), 1.12 (3H, t, J=7.2 Hz).

[2464] LCMS: m/z 299, 301 [M+H].sup.+

[2465] HPLC retention time: 2.52, 3.05 min (analysis condition S)

Example 395

Compound I2-3

4-(4-Chloro-3-methoxy-phenyl)-2-(4-cyano-2-nitro-phenyl)-4-methyl-3-oxo-pentanoic Acid Ethyl Ester

[2466] ##STR00410##

[2467] Under the same conditions as the method for synthesizing Compound K4, the title compound was obtained as a crude product from Compound I2-2.

Example 396

Compound I2-4

2-[1-(4-Chloro-3-methoxy-phenyl)-1-methyl-ethyl]-6-cyano-1H-indole-3-carboxylic acid ethyl ester

[2468] ##STR00411##

[2469] Under the same conditions as the method for synthesizing Compound K5, the title compound was obtained from Compound I2-3.

[2470] LCMS: m/z 397, 399 [M+H].sup.+

[2471] HPLC retention time: 2.83 min (analysis condition S)

Example 397

Compound I3

9-Chloro-8-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2472] ##STR00412##

[2473] (Method 1) Under the same conditions as the method for synthesizing Compound A4, the title compound was obtained from Compound I1-2.

[2474] (Method 2) Under the same conditions as the method for synthesizing Compound L8-1, the title compound was obtained from Compound I2-4.

[2475] .sup.1H-NMR (400 MHz, DMSO-d.sub.6) : 12.79 (1H, s), 8.27-8.31 (1H, m), 8.12 (1H, s), 8.00-8.02 (1H, m), 7.58-7.63 (1H, m), 7.51 (1H, s), 4.03 (3H, s), 1.80 (6H, s).

[2476] LCMS: m/z 351 [M+H].sup.+

[2477] HPLC retention time: 2.87 min (analysis condition U)

Example 398

Compound I4

9-Chloro-8-hydroxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2478] ##STR00413##

[2479] Under the same conditions as the method for synthesizing Compound E3-2, the title compound was prepared from Compound I3.

[2480] LCMS: m/z 337 [M+H].sup.+

[2481] HPLC retention time: 2.47 min (analysis condition U)

Example 399

Compound I5

Trifluoro-methanesulfonic Acid 9-chloro-3-cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl ester

[2482] ##STR00414##

[2483] Under the same conditions as the method for synthesizing Compound B1, the title compound was prepared from Compound I4.

[2484] LCMS: m/z 469 [M+H].sup.+

[2485] HPLC retention time: 3.40 min (analysis condition U)

Example 400

Compound I6-1

9-Chloro-6,6-dimethyl-11-oxo-8-(4-pyrrolidin-1-yl-piperidin-1-yl)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2486] ##STR00415##

[2487] Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound I5 and 4-pyrrolidin-1-yl-piperidine.

[2488] LCMS: m/z 473 [M+H].sup.+

[2489] HPLC retention time: 2.25 min (analysis condition U)

Example 401

Compound I6-2

9-Chloro-8-(4-isopropyl-piperazin-1-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2490] ##STR00416##

[2491] Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound I5.

[2492] LCMS: m/z 447 [M+H].sup.+

[2493] HPLC retention time: 2.30 min (analysis condition U)

Example 402

Compound I6-3

9-Chloro-6,6-dimethyl-8-morpholin-4-yl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2494] ##STR00417##

[2495] Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from 15 and morpholine.

[2496] .sup.1H-NMR (400 MHz, DMSO-d.sub.6) : 12.79 (1H, s), 8.28 (1H, d, 8.0 Hz), 8.09 (1H, s), 8.00 (1H, s), 7.59 (1H, d, 8.0 Hz), 7.45 (1H, s), 3.75-3.81 (4H, m), 3.13-3.19 (4H, m), 1.76 (6H, s)

[2497] LCMS: m/z 406 [M+H].sup.+

[2498] HPLC retention time: 2.88 min (analysis condition U)

Example 403

Compound I6-4

9-Chloro-6,6-dimethyl-8-(4-morpholin-4-yl-piperidin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2499] ##STR00418##

[2500] Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound I5 and 4-piperidin-4-yl-morpholine.

[2501] .sup.1H-NMR (400 MHz, DMSO-d.sub.6) : 12.75 (1H, s), 8.28 (1H, d, 8.0 Hz), 8.07 (1H, s), 8.00 (1H, s), 7.59 (1H, d, 8.0 Hz), 7.41 (1H, s), 3.55-3.62 (4H, m), 3.47-3.56 (4H, m), 2.75-2.86 (2H, m), 2.45- 2.55 (4H, m), 2.28-2.39 (1H, m), 1.86-1.96 (2H, m), 1.76 (6H, s), 1.52-1.66 (2H, m)

[2502] LCMS: m/z 489 [M+H].sup.+

[2503] HPLC retention time: 1.97 min (analysis condition U)

Example 404

Compound I6-5-1

[1-(9-Chloro-3-cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl)-piperidin-4-yl]-carbamic Acid Tert-Butyl Ester

[2504] ##STR00419##

[2505] Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound I5 and piperidin-4-yl-carbamic acid tert-butyl ester.

[2506] LCMS: m/z 519 [M+H].sup.+

[2507] HPLC retention time: 3.27 min (analysis condition U)

Example 405

Compound I6-5-2

8-(4-Amino-piperidin-1-yl)-9-chloro-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2508] ##STR00420##

[2509] Under the same conditions as the method for synthesizing Compound A8-1, the title compound was prepared from Compound I6-5-1.

[2510] LCMS: m/z 419 [M+H].sup.+

[2511] HPLC retention time: 2.12 min (analysis condition U)

Example 406

Compound I6-6

9-Chloro-6,6-dimethyl-11-oxo-8-piperazin-1-yl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2512] ##STR00421##

[2513] Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound I5 and piperazine.

[2514] LCMS: m/z 405 [M+H].sup.+

[2515] HPLC retention time: 1.87 min (analysis condition U)

Example 407

Compound I7-1

N-[1-(9-Chloro-3-cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl)-piperidin-4-yl]-methanesulfonamide

[2516] ##STR00422##

[2517] Under the same conditions as the method for synthesizing Compound A9-1, the title compound was prepared from Compound I6-5-2.

[2518] LCMS: m/z 497 [M+H].sup.+

[2519] HPLC retention time: 2.62 min (analysis condition U)

Example 408

Compound I7-2

9-Chloro-6,6-dimethyl-8-(4-oxetan-3-yl-piperazin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2520] ##STR00423##

[2521] Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound I5 and 1-oxetan-3-yl-piperazine.

[2522] .sup.1H-NMR (400 MHz, DMSO-d.sub.6) : 12.78 (1H, s), 8.27-8.31 (1H, m), 8.07-8.09 (1H, s), 7.99-8.02 (1H, m), 7.59-7.62 (1H, m), 7.44-7.46 (1H, s), 4.54-4.60 (2H, m), 4.44-4.51 (2H, m), 3.47-3.55 (1H, m), 3.16-3.24 (4H, m), 2.40-2.55 (4H, m), 1.77 (6H, s)

[2523] LCMS: m/z 461 [M+H].sup.+

[2524] HPLC retention time: 2.13 min (analysis condition U)

Example 409

Compound I7-3

9-Chloro-8-(4-cyclopropyl-piperazin-1-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2525] ##STR00424##

[2526] Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound I5 and 1-cyclopropylpiperazine.

[2527] LCMS: m/z 445 [M+H].sup.+

[2528] HPLC retention time: 1.97 min (analysis condition U)

Example 410

Compound I7-4

9-Chloro-8-(4-cyclobutyl-piperazin-1-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2529] ##STR00425##

[2530] Under the same conditions as the method for synthesizing Compound B3-32, the title compound was prepared from Compound I6-6 and cyclobutanone.

[2531] .sup.1H-NMR (400 MHz, DMSO-d.sub.6) : 12.78 (1H, s), 8.29 (1H, d, 8.5 Hz), 8.08 (1H, s), 8.01 (1H, s), 7.60 (1H, d, 8.5 Hz), 7.44 (1H, s), 3.17-3.15 (4H, m), 2.83-2.76 (1H, m), 2.47-2.44 (4H, m), 2.04- 1.97 (2H, m), 1.82 (2H, t, 9.8 Hz), 1.77 (6H, s), 1.70-1.63 (2H, m)

[2532] LCMS: m/z 459, 461 [M+H].sup.+

[2533] HPLC retention time: 1.63 min (analysis condition S)

Example 411

Compound J2

6-Methoxy-1,1-dimethyl-3,4-dihydro-1H-naphthalen-2-one

[2534] ##STR00426##

[2535] Under the same conditions as the method for synthesizing Compound A2, the title compound was prepared from 6-methoxy-3,4-dihydro-1H-naphthalen-2-one and iodomethane.

[2536] LCMS: m/z 205 [M+H].sup.+

[2537] HPLC retention time: 1.54 min (analysis condition S)

Example 412

Compound J3-1

9-Methoxy-6,6-dimethyl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2538] ##STR00427##

[2539] Under the same conditions as the method for synthesizing Compound E2-1, the title compound was prepared from Compound J2 and 3-hydrazino-benzonitrile.

[2540] LCMS: m/z 303 [M+H].sup.+

[2541] HPLC retention time: 2.73 min (analysis condition S)

Example 413

Compound J3-2

9-Methoxy-6,6-dimethyl-6,11-dihydro-5H-benzo[b]carbazole-1-carbonitrile

[2542] ##STR00428##

[2543] Compound J3-2 was obtained as a by-product of the synthesis of Compound J3-1.

[2544] LCMS: m/z 303 [M+H].sup.+

[2545] HPLC retention time: 2.67 min (analysis condition S)

Example 414

Compound J4

9-Methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2546] ##STR00429##

[2547] Under the same conditions as the method for synthesizing Compound A4, the title compound was prepared from Compound J3-1 and Compound J3-2 (mixture).

[2548] .sup.1H-NMR (DMSO-d.sub.6) : 12.79 (1H, s), 8.33 (1H, d, J=8.2 Hz), 8.02 (1H, s), 7.81 (1H, d, J=8.6 Hz), 7.69 (1H, d, J=3.0 Hz), 7.63 (1H, dd, J=8.3, 1.4 Hz), 7.28 (1H, dd, J=8.7, 3.0 Hz), 3.87 (3H, s), 1.74 (6H, s).

[2549] LCMS: m/z 317 [M+H].sup.+

[2550] HPLC retention time: 2.25 min (analysis condition S)

Example 415

Compound J5

9-Hydroxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2551] ##STR00430##

[2552] Under the same conditions as the method for synthesizing Compound A6, the title compound was prepared from Compound J4.

[2553] .sup.1H-NMR (DMSO-d.sub.6) : 12.75 (1H, s), 9.77 (1H, s), 8.32 (1H, dd, J=8.2, 0.7 Hz), 8.01 (1H, s), 7.68 (1H, d, J=8.6 Hz), 7.62 (1H, dd, J=8.2, 1.4 Hz), 7.58 (1H, d, J=2.8 Hz), 7.10 (1H, dd, J=8.6, 2.8 Hz), 1.72 (6H, s).

[2554] LCMS: m/z 303 [M+H].sup.+

[2555] HPLC retention time: 1.75 min (analysis condition S)

Example 416

Compound J6

Trifluoro-methanesulfonic Acid 3-cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-9-yl ester

[2556] ##STR00431##

[2557] Under the same conditions as the method for synthesizing Compound B1, the title compound was prepared from Compound J5.

[2558] .sup.1H-NMR (DMSO-d.sub.6) : 12.95 (1H, s), 8.31 (1H, d, J=8.2 Hz), 8.15 (2H, m), 8.05 (1H, s), 7.87 (1H, dd, J=9.0, 2.7 Hz), 7.65 (1H, d, J=8.2 Hz), 1.80 (6H, s).

[2559] LCMS: m/z 435 [M+H].sup.+

[2560] HPLC retention time: 2.75 min (analysis condition S)

Example 417

Compound J7-1

9-Isopropoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2561] ##STR00432##

[2562] Under the same conditions as the method for synthesizing Compound A7-1, the title compound was prepared from Compound J4 and isopropanol.

[2563] LCMS: m/z 345 [M+H].sup.+

[2564] HPLC retention time: 3.87 min (analysis condition W)

Example 418

Compound J7-2-1

4-(3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-9-yl oxy)-piperidine-1-carboxylic acid tert-butyl ester

[2565] ##STR00433##

[2566] Under the same conditions as the method for synthesizing Compound A7-1, the title compound was prepared from Compound J5.

[2567] LCMS: m/z 486 [M+H].sup.+

[2568] HPLC retention time: 4.15 min (analysis condition W)

Example 419

Compound J7-2-2

6,6-Dimethyl-11-oxo-9-(piperidin-4-yl oxy)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2569] ##STR00434##

[2570] Under the same conditions as the method for synthesizing Compound A8-1, the title compound was prepared from Compound J7-2-1.

[2571] LCMS: m/z 386 [M+H].sup.+

[2572] HPLC retention time: 2.48 min (analysis condition W)

Example 420

Compound J7-2-3

6,6-Dimethyl-9-(1-oxetan-3-yl-piperidin-4-yl oxy)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2573] ##STR00435##

[2574] Under the same conditions as the method for synthesizing Compound B3-32, the title compound was prepared from Compound J7-2-2 and oxetan-3-one.

[2575] LCMS: m/z 442 [M+H].sup.+

[2576] HPLC retention time: 2.61 min (analysis condition W)

Example 421

Compound J7-3

6,6-Dimethyl-11-oxo-9-(4-pyrrolidin-1-yl-piperidin-1-yl)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2577] ##STR00436##

[2578] Under the same conditions as the method for synthesizing Compound B2-10, the title compound was prepared from Compound J6 and 4-pyrrolidin-1-yl-piperidine.

[2579] .sup.1H-NMR (270 MHz, DMSO-d.sub.6) : 13.12 (1H, s), 8.32 (1H, d, J=8.1 Hz), 8.01 (1H, s), 7.72 (1H, d, J=8.7 Hz), 7.68 (1H, d, J=2.6 Hz), 7.62 (1H, dd, J=8.2, 1.2 Hz), 7.38 (1H, dd, J=9.1, 2.8 Hz), 3.90 (2H, d, J=11.5 Hz), 2.76 (2H, t, J=12.2 Hz), 2.14 (2H, d, J=10.9 Hz), 1.91 (4H, br), 1.74 (6H, s).

[2580] LCMS: m/z 439 [M+H].sup.+

[2581] HPLC retention time: 1.35 min (analysis condition S)

Example 422

Compound J7-4

9-(4-Isopropyl-piperazin-1-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2582] ##STR00437##

[2583] Under the same conditions as the method for synthesizing Compound B2-10, the title compound was prepared from Compound J6 and 1-isopropyl-piperazine.

[2584] .sup.1H-NMR (270 MHz, DMSO-d.sub.6) : 12.80 (1H, s), 8.33 (1H, d, J=7.6 Hz), 8. 02 (1H, s), 7.66 (3H, m), 7.33 (1H, d, J=8.2 Hz), 3.21 (4H, br), 2.66 (5H, m), 1.72 (6H, s), 1.02 (6H, d, J=6.3 Hz).

[2585] LCMS: m/z 413 [M+H].sup.+

[2586] HPLC retention time: 1.38 min (analysis condition S)

Example 423

Compound J7-5

6,6-Dimethyl-11-oxo-9-pyrrolidin-1-yl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2587] ##STR00438##

[2588] Under the same conditions as the method for synthesizing Compound B2-10, the title compound was prepared from Compound J6 and pyrrolidine.

[2589] .sup.1H-NMR (270 MHz, DMSO-d.sub.6) : 8.24 (1H, d, J=8.1 Hz), 7.91 (1H, s), 7.59 (1H, d, J=8.6 Hz), 7.45 (1H, d, J=7.9 Hz), 7.30 (1H, d, J=2.6 Hz), 6.85 (1H, dd, J=8.6, 2.8 Hz), 3.31 (4H, t, J=6.3 Hz), 1.99 (4H, t, J=6.2 Hz), 1.67 (6H, s).

[2590] LCMS: m/z 356 [M+H].sup.+

[2591] HPLC retention time: 2.38 min (analysis condition S)

Example 424

Compound J7-6

6,6-Dimethyl-11-oxo-9-((S)-2-pyrrolidin-1-yl methyl-pyrrolidin-1-yl)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2592] ##STR00439##

[2593] Under the same conditions as the method for synthesizing Compound B2-10, the title compound was prepared from Compound J6 and (S)-2-pyrrolidin-1-yl methyl-pyrrolidine.

[2594] LCMS: m/z 439 [M+H].sup.+

[2595] HPLC retention time: 1.50 min (analysis condition S)

Example 425

Compound J7-7

6,6-Dimethyl-11-oxo-9-piperazin-1-yl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2596] ##STR00440##

[2597] Under the same conditions as the method for synthesizing Compound B2-10, the title compound was prepared from Compound J6 and piperazine.

[2598] LCMS: m/z 371 [M+H].sup.+

[2599] HPLC retention time: 1.31 min (analysis condition S)

Example 426

Compound J7-8

9-(3-Hydroxy-3-methyl-but-1-ynyl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2600] ##STR00441##

[2601] Under the same conditions as the method for synthesizing Compound E4-2-1, the title compound was prepared from Compound J6.

[2602] LCMS: m/z 369 [M+H].sup.+

[2603] HPLC retention time: 2.16 min (analysis condition S)

Example 427

Compound J7-9

9-Ethynyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2604] ##STR00442##

[2605] Under the same conditions as the method for synthesizing Compound E4-2-2, the title compound was prepared from Compound J7-8.

[2606] .sup.1H-NMR (270 MHz, DMSO-d.sub.6) : 8.31 (1H, d, J=8.1 Hz), 8.23 (1H, d, J=1.8 Hz), 8.02 (1H, d, J=1.3 Hz), 7.93 (1H, d, J=8.2 Hz), 7.78 (1H, dd, J=8.2, 1.8 Hz), 7.61 (1H, dd, J=8.1, 1.3 Hz), 4.31 (1H, s), 1.77 (6H, s).

[2607] LCMS: m/z 311 [M+H].sup.+

[2608] HPLC retention time: 2.40 min (analysis condition S)

Example 428

Compound J7-10-1

4-(3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-9-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester

[2609] ##STR00443##

[2610] Under the same conditions as the method for synthesizing Compound B2-22-1, the title compound was prepared from Compound J6.

[2611] LCMS: m/z 468 [M+H].sup.+

[2612] HPLC retention time: 2.90 min (analysis condition S)

Example 429

Compound J7-10-2

6,6-Dimethyl-11-oxo-9-(1,2,3,6-tetrahydro-pyridin-4-yl)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2613] ##STR00444##

[2614] Under the same conditions as the method for synthesizing Compound A8-1, the title compound was prepared from Compound J7-10-1.

[2615] LCMS: m/z 368 [M+H].sup.+

[2616] HPLC retention time: 1.27 min (analysis condition S)

Example 430

Compound J7-11-1

9-(Piperidin-4-ylmethyl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2617] ##STR00445##

[2618] Under the same conditions as the method for synthesizing Compound B2-25-1 and Compound B2-25-2, the title compound was prepared from Compound J6.

[2619] LCMS: m/z 384 [M+H].sup.+

[2620] HPLC retention time: 1.42 min (analysis condition S)

Example 431

Compound J7-11-2

9-(1-Isopropyl-piperidin-4-ylmethyl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2621] ##STR00446##

[2622] Under the same conditions as the method for synthesizing Compound B3-32, the title compound was prepared from Compound J7-11-1 and acetone.

[2623] .sup.1H-NMR (400 MHz, DMSO-d.sub.6) : 12.79 (1H, s), 8.33 (1H, d, 7.9 Hz), 8.01 (1H, s), 7.98 (1H, d, 1.8 Hz), 7.79 (1H, d, 7.9 Hz), 7.61 (1H, d, 7.9 Hz), 7.51-7.49 (1H, m), 2.74 (2H, d, 11.0 Hz), 2.64-2.60 (3H, m), 2.04 (2H, t, 10.7 Hz), 1.77 (6H, s), 1.60-1.51 (3H, m), 1.23-1.14 (2H, m), 0.94 (6H, d, 6.7 Hz)

[2624] LCMS: m/z 426 [M+H].sup.+

Example 432

Compound J7-12

4-(3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-9-yl oxy)-butyric Acid

[2625] ##STR00447##

[2626] 9-Hydroxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (Compound J5, 30 mg, 0.099 mmol), 4-bromo-butyric acid methyl ester (24.9 l, 0.198 mmol) and cesium carbonate (64.5 mg, 0.198 mmol) were dissolved in DMA (0.20 ml) and stirred at room temperature for 4 hr. Water was added to the reaction solution, which was then extracted with diethyl ether. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The yellow solid obtained after concentration under reduced pressure was purified by silica gel column chromatography (methylene chloride/MeOH) to obtain 4-(3-cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-9-yl oxy)-butyric acid methyl ester as an intermediate.

[2627] The intermediate was dissolved in MeOH (0.50 ml), added with aqueous solution of sodium hydroxide (6 mol/1) and stirred at room temperature for 30 min. The reaction solution was added with hydrochloric acid (3 mol/1), extracted with diethyl ether. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. After concentration under reduced pressure, white solid was obtained, which was then washed with methylene chloride to obtain the title compound (19.0 mg, 70%).

[2628] LCMS: m/z 389 [M+H].sup.+

[2629] HPLC retention time: 2.39 min (analysis condition F)

Example 433

Compound J7-13

5-(3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-9-yl oxy)-pentanoic Acid

[2630] ##STR00448##

[2631] Under the same conditions as the method for synthesizing Compound J7-12, Compound J5 and 5-bromo-pentanoic acid methyl ester were reacted to obtain the target compound (19.5 mg, 64%).

[2632] LCMS: m/z 403 [M+H].sup.+

[2633] HPLC retention time: 2.49 min (analysis condition F)

Example 434

Compound J7-14

6-(3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-9-yl oxy)-hexanoic Acid

[2634] ##STR00449##

[2635] Under the same conditions as the method for synthesizing Compound J7-12, Compound J5 and 6-bromo-hexanoic acid ethyl ester were reacted to obtain the target compound (19.6 mg, 66%).

[2636] LCMS: m/z 417 [M+H].sup.+

[2637] HPLC retention time: 2.61 min (analysis condition F)

Example 435

Compound J7-15

3-[2-(3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-9-yl oxy)-ethoxy]-propionic Acid

[2638] ##STR00450##

[2639] Under the same conditions as the method for synthesizing Compound A7-1, Compound JJ2 and 3-(2-hydroxy-ethoxy)-propionic acid tert-butyl ester were reacted to obtain 3-[2-(3-bromo-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-9-yl oxy)-ethoxy]-propionic acid tert-butyl ester.

[2640] The resultant was dissolved in DMA (0.30 ml), added with copper cyanide (25.5 mg, 0.285 mmol), and stirred at 200 C. for 1 hr under irradiation with microwave. The reaction solution was diluted with ethyl acetate, washed with saturated brine and dried over anhydrous magnesium sulfate. The residues obtained after concentration under reduced pressure were dissolved in methylene chloride (0.75 ml). The solution was added with TFA (250 l) and stirred at room temperature for 5 min. Thereafter, the residues obtained from the reaction solution after concentration under reduced pressure were purified by silica gel column chromatography (methylene chloride/MeOH) to obtain the title compound (5.6 mg, 14%).

[2641] LCMS: m/z 419 [M+H].sup.+

[2642] HPLC retention time: 2.31 min (analysis condition F)

Example 436

Compound J7-16

6,6-Dimethyl-11-oxo-9-(pyridin-4-yl methoxy)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2643] ##STR00451##

[2644] Under the same conditions as the method for synthesizing Compound A7-1, the title compound was prepared from Compound J5 and pyridin-4-yl-methanol (pale yellow solid, 6.1 mg, 31%).

[2645] LCMS: m/z 394 [M+H].sup.+

[2646] HPLC retention time: 1.97 min (analysis condition F)

Example 437

Compound J7-17

6,6-Dimethyl-11-oxo-9-(pyridin-3-yl methoxy)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2647] ##STR00452##

[2648] Under the same conditions as the method for synthesizing Compound JJ3-1, the title compound was prepared from Compound J5 and pyridin-3-yl-methanol (pale yellow solid, 7.9 mg, 38%).

[2649] LCMS: m/z 394 [M+H].sup.+

[2650] HPLC retention time: 1.99 min (analysis condition F)

Example 438

Compound J8-1

6,6-Dimethyl-9-(4-oxetan-3-yl-piperazin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2651] ##STR00453##

[2652] Under the same conditions as the method for synthesizing Compound B3-32, the title compound was prepared from Compound J7-7 and oxetan-3-one.

[2653] LCMS: m/z 427 [M+H].sup.+

[2654] HPLC retention time: 1.31 min (analysis condition S)

Example 439

Compound J8-2

9-(4-Cyclopropyl-piperazin-1-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2655] ##STR00454##

[2656] Under the same conditions as the method for synthesizing Compound B3-32, the title compound was prepared from Compound J7-7 and (1-ethoxy cyclopropoxy)trimethylsilane.

[2657] LCMS: m/z 411 [M+H].sup.+

[2658] HPLC retention time: 1.39 min (analysis condition S)

Example 440

Compound J8-3

9-(1-Methanesulfonyl-1,2,3,6-tetrahydro-pyridin-4-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2659] ##STR00455##

[2660] Under the same conditions as the method for synthesizing Compound A9-1, the title compound was prepared from Compound J7-10-2.

[2661] .sup.1H-NMR (400 MHz, DMSO-d.sub.6) : 12.81 (1H, s), 8.33 (1H, d, 7.9 Hz), 8.26 (1H, d, 2.4 Hz), 8.01 (1H, s), 7.88-7.81 (2H, m), 7.61 (1H, d, 7.9 Hz), 6.36 (1H, s), 3.93 (2H, d, 3.0 Hz), 3.45 (2H, t, 5.8 Hz), 2.97 (3H, s), 2.73-2.70 (2H, m), 1.78 (6H, s)

[2662] LCMS: m/z 446 [M+H].sup.+

[2663] HPLC retention time: 2.15 min (analysis condition S)

Example 441

Compound J8-4

9-(1-Isopropyl-1,2,3,6-tetrahydro-pyridin-4-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2664] ##STR00456##

[2665] Under the same conditions as the method for synthesizing Compound B3-32, the title compound was prepared from Compound J7-10-2 and acetone.

[2666] .sup.1H-NMR (400 MHz, DMSO-d.sub.6) : 12.82 (1H, s), 8.33 (1H, d, 7.9 Hz), 8.22 (1H, d, 1.8 Hz), 8.02 (1H, s), 7.84 (1H, d, 8.5 Hz), 7.78 (1H, dd, 8.2, 2.1 Hz), 7.62 (1H, d, 7.9 Hz), 6.32 (1H, t, 3.7 Hz), 3.23-3.20 (2H, m), 2.83-2.76 (1H, m), 2.72 (2H, t, 5.5 Hz), 2.56-2.54 (2H, m), 1.78 (6H, s), 1.06 (6H, d, 6.7 Hz)

[2667] LCMS: m/z 410 [M+H].sup.+

[2668] HPLC retention time: 1.38 min (analysis condition S)

Example 442

Compound J8-5

6,6-Dimethyl-9-(1-oxetan-3-yl-1,2,3,6-tetrahydro-pyridin-4-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2669] ##STR00457##

[2670] Under the same conditions as the method for synthesizing Compound B3-32, the title compound was prepared from Compound J7-10-2 and oxetan-3-one.

[2671] .sup.1H-NMR (270 MHz, DMSO-d.sub.6) : 12.81 (1H, br. s), 8.34 (1H, d, J=8.2 Hz), 8.22 (1H, d, J=1.8 Hz), 8.03 (1H, s), 7.76-7.90 (2H, m), 7.64 (1H, dd, J=8.2, 1.8 Hz), 6.25-6.34 (1H, m), 4.60 (2H, dd, J=6.6, 6.0 Hz), 4.52 (2H, dd, J=6.6, 6.0 Hz), 3.57 (1H, t, J=6.0 Hz), 3.03 (2H, m), 2.55 (4H, m), 1.77 (6H, s).

[2672] LCMS: m/z 424 [M+H].sup.+

[2673] HPLC retention time: 1.34 min (analysis condition S)

Example 443

Compound J8-6

9-(1-Cyclopropyl-1,2,3,6-tetrahydro-pyridin-4-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2674] ##STR00458##

[2675] Under the same conditions as the method for synthesizing Compound B3-32, the title compound was prepared from Compound J7-10-2 and (1-ethoxycyclopropoxy)trimethylsilane.

[2676] LCMS: m/z 408 [M+H].sup.+

[2677] HPLC retention time: 1.36 min (analysis condition S)

Example 444

Compound J9-1

4-(3-Cyano-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-9-yl)-piperidine-1-carboxylic Acid Tert-Butyl Ester

[2678] ##STR00459##

[2679] Under the same conditions as the method for synthesizing Compound B3-13-1, the title compound was prepared from Compound J7-10-1.

[2680] LCMS: m/z 414, 470 [M+H].sup.+

[2681] HPLC retention time: 2.83 min (analysis condition S)

Example 445

Compound J9-2

6,6-Dimethyl-11-oxo-9-piperidin-4-yl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2682] ##STR00460##

[2683] Under the same conditions as the method for synthesizing Compound A8-1, the title compound was prepared from Compound J9-1.

[2684] LCMS: m/z 370 [M+H].sup.+

[2685] HPLC retention time: 1.30 min (analysis condition S)

Example 446

Compound J9-3

9-(1-Isopropyl-piperidin-4-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2686] ##STR00461##

[2687] Under the same conditions as the method for synthesizing Compound A9-1, the title compound was prepared from Compound J9-2 and 2-bromopropane.

[2688] .sup.1H-NMR (270 MHz, DMSO-d.sub.6) : 12.83 (1H, s), 8.34 (2H, d, J=8.1 Hz), 8.05 (2H, m), 7.82 (1H, d, J=8.1 Hz), 7.61 (2H, m), 3.02 (2H, br), 2.42 (2H, br), 1.76 (6H, s), 1.06 (6H, d, J=6.4 Hz).

[2689] LCMS: m/z 412 [M+H].sup.+

[2690] HPLC retention time: 1.45 min (analysis condition S)

Example 447

Compound J9-4

6,6-Dimethyl-9-(1-oxetan-3-yl-piperidin-4-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2691] ##STR00462##

[2692] Under the same conditions as the method for synthesizing Compound B3-13-1, the title compound was prepared from Compound J8-5.

[2693] LCMS: m/z 426 [M+H].sup.+

[2694] HPLC retention time: 1.26 min (analysis condition S)

Example 448

Compound J9-5

9-(1-Cyclopropyl-piperidin-4-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2695] ##STR00463##

[2696] Under the same conditions as the method for synthesizing Compound B3-13-1, the title compound was prepared from Compound J8-6.

[2697] LCMS: m/z 410 [M+H].sup.+

[2698] HPLC retention time: 1.43 min (analysis condition S)

Example 449

Compound JJ1

3-Bromo-9-methoxy-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one

[2699] ##STR00464##

[2700] 6-Methoxy-1,1-dimethyl-3,4-dihydro-1H-naphthalen-2-one (Compound J2, 2.15 g, 10.5 mmol) and 3-bromophenylhydrazine hydrochloric acid salt (3.11 g, 1.3 eq.) were dissolved in acetic acid (12 mL), and stirred at 100 C. for 2.5 hr under nitrogen atmosphere. After cooling, the reaction solution was added with ethyl acetate, washed with water, saturated aqueous solution of sodium hydrogen carbonate, and saturated brine, and dried over magnesium sulfate. After the filtration, it was concentrated under reduced pressure. The resulting residues were dissolved in THF (30 mL) and water (3 mL), added with DDQ (5.96 g, 2.5 eq.) at 0 C., and then stirred at room temperature overnight. The reaction solution was added with MTBE, washed with 0.5 N aqueous solution of sodium hydroxide and saturated brine, and dried over magnesium sulfate. After filtration and the concentration under reduced pressure, the resulting residues were washed with MTBE to obtain the title compound (brown solid, 1.80 g, 46%).

[2701] .sup.1H-NMR (270 MHz, DMSO-d.sub.6) : 12.4 (1H, s), 8.12 (1H, d, J=8.6 Hz), 7.79 (1H, d, J=8.9 Hz), 7.67-7.68 (2H, m), 7.40 (1H, dd, J=1.7, 8.6 Hz), 7.26 (1H, dd, J=2.6, 8.9 Hz), 3.86 (3H, s), 1.72 (6H, s),

[2702] LCMS: m/z 370 [M+H].sup.+

[2703] HPLC retention time: 6.45 min (analysis condition H)

Example 450

Compound JJ2

3-Bromo-9-hydroxy-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one

[2704] ##STR00465##

[2705] 3-Bromo-9-methoxy-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one (Compound JJ1, 1.50 g, 4.05 mmol) and pyridinium chloride (15.2 g, 32.5 eq.) were stirred at 160 C. for 12 hr under nitrogen atmosphere. After cooling, water and ethyl acetate were added and the resulting suspension was filtered. The organic layer was washed with water and saturated brine and dried over magnesium sulfate. After filtration and the concentration under reduced pressure, the resulting residues were washed with MTBE to obtain the title compound (brown solid, 1.47 g, 100%).

[2706] .sup.1H-NMR (270 MHz, DMSO-d.sub.6) : 12.4 (1H, s), 9.71 (1H, s), 8.11 (1H, d, J=8.2 Hz), 7.64-7.68 (2H, m), 7.57 (1H, d, J=3.0 Hz), 7.38 (1H, dd, J=1.7, 8.2 Hz), 7.07 (1H, dd, J=3.0, 8.6 Hz), 1.69 (6H, s),

[2707] LCMS: m/z 356 [M+H].sup.+

[2708] HPLC retention time: 2.52 min (analysis condition F)

Example 451

Compound JJ3-1

3-Bromo-9-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy)-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one

[2709] ##STR00466##

[2710] Under nitrogen atmosphere, 3-bromo-9-hydroxy-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one (Compound JJ2, 356 mg, 1.00 mmol) and triphenylphosphine (317 mg, 1.2 eq.) were added with THF (3 ml), followed by dropwise addition of ((S)-2,2-dimethyl-[1,3]dioxolan-4-yl)-methanol (148 l, 1.2 eq.) and diisopropyl azodicarboxylic acid (252 l, 1.3 eq.). The mixture was then stirred at 50 C. for 2 hr. After cooling, the reaction solution was added with ethyl acetate, washed with brine and dried over magnesium sulfate. After filtration and the concentration under reduced pressure, the resulting residues were purified by silica gel column chromatography (ethyl acetate/dichloromethane) to yield the solid, which was then washed with dichloromethane to obtain the title compound (white powder, 241.6 mg, 51%).

[2711] .sup.1H-NMR (270 MHz, DMSO-d.sub.6) : 12.4 (1H, s), 8.12 (1H, d, J=8.2 Hz), 7.79 (1H, d, J=8.9 Hz), 7.67-7.69 (2H, m), 7.40 (1H, dd, J=1.8, 8.2 Hz), 7.28 (1H, dd, J=3.0, 8.9 Hz), 4.41-4.48 (1H, m), 4.06-4.17 (2H, m), 3.79-3.85 (1H, m), 1.72 (3H, s), 1.38 (3H, s), 1.33 (3H, s),

[2712] LCMS: m/z 470 [M+H].sup.+

[2713] HPLC retention time: 3.08 min (analysis condition F)

Example 452

Compound JJ3-2

3-Bromo-9-((R)-2,3-dihydroxy-propoxy)-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one

[2714] ##STR00467##

[2715] 3-Bromo-9-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy)-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one (Compound JJ3-1, 18.7 mg, 0.0398 mmol) was dissolved in methanol (1 mL) and THF (0.3 mL), added with 1 N hydrochloric acid (5 drops) and stirred at 50 C. for 1 hr. After cooling, the reaction solution was concentrated under reduced pressure, and the resulting residues were added with dichloromethane, and the solid was separated by filtration to obtain the title compound (yellow powder, 16.8 mg, 98%).

[2716] .sup.1H-NMR (270 MHz, DMSO-d.sub.6) : 12.43 (1H, s), 8.12 (1H, d, J=8.6 Hz), 7.78 (1H, d, J=8.9 Hz), 7.67-7.70 (2H, m), 7.40 (2H, dd, J=1.8, 8.6 Hz), 7.27 (2H, dd, J=2.8, 8.9 Hz), 4.43 (2H, brs), 4.12 (1H, dd, J=9.9, 4.3 Hz), 3.96 (1H, dd, J=9.7, 6.1 Hz), 3.85 (1H, dd, J=9.9, 5.6 Hz), 3.48 (2H, d, J=5.6 Hz), 1.72 (6H, s),

[2717] LCMS: m/z 430 [M+H].sup.+

[2718] HPLC retention time: 2.02 min (analysis condition F)

Example 453

Compound JJ4-1

3-Bromo-9-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy)-5,6,6-trimethyl-5,6-dihydro-benzo[b]carbazol-11-one

[2719] ##STR00468##

[2720] To the mixture of 3-bromo-9-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy)-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one (Compound JJ3-1, 33.2 mg, 0.0706 mmol) and sodium hydride (60% in oil, 6.4 mg, 2.3 eq.), DMA (0.55 mL) and methyl iodide (0.015 mL, 3.4 eq.) were added under nitrogen atmosphere at 0 C., and the mixture was stirred at room temperature overnight. The reaction solution was added with water and extracted with ethyl acetate. The organic layer was washed with brine and dried over magnesium sulfate. After filtration and the concentration under reduced pressure, the resulting solid was washed with MTBE to obtain the title compound (white solid, 31.2 mg, 91%).

[2721] LCMS: m/z 484 [M+H].sup.+

[2722] HPLC retention time: 3.34 min (analysis condition F)

Example 454

Compound JJ4-2

3-Bromo-9-((R)-2,3-dihydroxy-propoxy)-5,6,6-trimethyl-5,6-dihydro-benzo[b]carbazol-11-one

[2723] ##STR00469##

[2724] Under the same conditions as the method for synthesizing Compound JJ3-2, the title compound was prepared from Compound JJ4-1 (yellow solid, 13.3 mg, 83%).

[2725] LCMS: m/z 444 [M+H].sup.+

[2726] HPLC retention time: 2.47 min (analysis condition F)

Example 455

Compound JJ5

(3-Bromo-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-9-yl oxy)-acetic acid

[2727] ##STR00470##

[2728] Under the same conditions as the method for synthesizing Compound A7-1, (3-bromo-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-9-yl oxy)-acetic acid methyl ester was prepared from Compound JJ2 and hydroxy-acetic acid methyl ester. The resultant was dissolved in MeOH (0.35 ml), added with aqueous solution of sodium hydroxide (6 mol/1), and stirred at room temperature for 10 min. The reaction solution was added with hydrochloric acid (3 mol/1), extracted with diethyl ether and dried over anhydrous magnesium sulfate. After the concentration under reduced pressure, white solid was obtained, which was then washed with methylene chloride to obtain the title compound (11.2 mg, 48%).

[2729] LCMS: m/z 414 [M+H].sup.+

[2730] HPLC retention time: 2.50 min (analysis condition F)

Example 456

Compound JJ6

4-(3-Bromo-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-9-yl oxy)-butyric Acid

[2731] ##STR00471##

[2732] 3-Bromo-9-hydroxy-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one (Compound JJ2, 20 mg, 0.056 mmol), 4-bromo-butyric acid methyl ester (7.0 l, 0.056 mmol) and cesium carbonate (36.6 mg, 0.112 mmol) were dissolved in DMA (0.09 ml), and then stirred at room temperature for 1 hr. Thereafter, 4-bromo-butyric acid methyl ester (7.0 l, 0.056 mmol) was added thereto and the mixture was stirred at room temperature for 3 hr, followed by further stirring at 45 C. for 30 min. The reaction solution was added with water, extracted with diethyl ether and dried over anhydrous magnesium sulfate. After the concentration under reduced pressure, the resulting residues were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain 4-(3-bromo-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-9-yl oxy)-butyric acid methyl ester. This compound was dissolved in MeOH (0.50 ml), added with aqueous solution of sodium hydroxide (6 mol/1), and then stirred at room temperature for 10 min. The reaction solution was added with hydrochloric acid (3 mol/1), extracted with diethyl ether, and dried over anhydrous magnesium sulfate and concentrated under reduced pressure to obtain white solid. This white solid was washed with methylene chloride to obtain the title compound (6.1 mg, 25%).

[2733] LCMS: m/z 442 [M+H].sup.+

[2734] HPLC retention time: 2.65 min (analysis condition F)

Example 457

Compound JJ7-1

3-Bromo-9-[(4R,5R)-5-(tert-butyl-dimethyl-[1,3]dioxolan-4-yl methoxy]-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one

[2735] ##STR00472##

[2736] Under the same conditions as the method for synthesizing Compound A7-1, the title compound (white solid, 111.5 mg, 65%) was prepared from Compound JJ2 and [(4R,5R)-5-(tert-butyl-dimethyl-silanyloxymethyl)-2,2-dimethyl-[1,3]dioxolan-4-yl]-methanol.

[2737] LCMS: m/z 614 [M+H].sup.+

[2738] HPLC retention time: 4.04 min (analysis condition F)

Example 458

Compound JJ7-2

3-Bromo-6,6-dimethyl-9-((2R,3R)-2,3,4-trihydroxy-butoxy)-5,6-dihydro-benzo[b]carbazol-11-one

[2739] ##STR00473##

[2740] 3-Bromo-9-[(4R,5R)-5-(tert-butyl-dimethyl-[1,3]dioxolan-4-yl methoxy]-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one (Compound JJ7-1, 13.7 mg, 0.0223 mmol) was dissolved in THF (0.15 mL) and methanol (0.1 mL), added with 0.5 M sulfuric acid (0.05 mL), and then stirred at 60 C. for 3 hr. After cooling, the reaction solution was added with saturated aqueous solution of sodium hydrogen carbonate and extracted with ethyl acetate. The organic layer was washed with brine and dried over magnesium sulfate. After filtration and the concentration under reduced pressure, the resulting solid was washed with dichloromethane to obtain the title compound (white solid, 8.4 mg, 82%).

[2741] LCMS: m/z 460 [M+H].sup.+

[2742] HPLC retention time: 2.18 min (analysis condition F)

Example 459

Compound JJ8-1

9-[(4R,5R)-5-(Tert-butyl-dimethyl-silanyloxymethyl)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy]-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2743] ##STR00474##

[2744] According to the same method as the method for synthesizing Compound A5-2, the title compound (11.1 mg, 50%) was prepared from Compound JJ7-1 and [(4R,5R)-5-(tert-butyl-dimethyl-silanyloxymethyl)-2,2-dimethyl-[1,3]dioxolan-4-yl]-methanol.

[2745] LCMS: m/z 561 [M+H].sup.+

[2746] HPLC retention time: 3.84 min (analysis condition F)

Example 460

Compound JJ8-2

6,6-Dimethyl-11-oxo-9-((2R,3R)-2,3,4-trihydroxy-butoxy)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2747] ##STR00475##

[2748] Under the same conditions as the method for synthesizing Compound JJ7-2, the title compound was prepared from 9-[(4R,5R)-5-(tert-butyl-dimethyl-silanyloxymethyl)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy]-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (Compound JJ8-1) (white solid, 7.8 mg, 97%).

[2749] LCMS: m/z 407 [M+H].sup.+

[2750] HPLC retention time: 1.92 min (analysis condition F)

Example 461

Compound JJ9-1

9-((R)-2,3-Dihydroxy-propoxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2751] ##STR00476##

[2752] 3-Bromo-9-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy)-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one (Compound JJ3-1, 49.5 mg, 0.105 mmol) and copper cyanide (90%, 35.3 mg, 3.4 eq.) were added with DMA (0.5 mL), and the mixture was irradiated with microwave at 200 C. for 1 hr under nitrogen atmosphere. After cooling, the reaction solution was added with water and extracted with ethyl acetate. The insoluble matters were separated off by filtration, and the organic layer was washed with brine and dried over magnesium sulfate. After filtration and the concentration under reduced pressure, the resulting residues were purified by preparative TLC (methanol/dichloromethane) to obtain the title compound (white solid, 8.5 mg, 22%).

[2753] LCMS: m/z 377 [M+H].sup.+

[2754] HPLC retention time: 2.02 min (analysis condition F)

Example 462

Compound JJ9-2

9-((S)-2,2-Dimethyl-[1,3]dioxolan-4-yl methoxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2755] ##STR00477##

[2756] The title compound was obtained as a by-product of the synthesis of Compound JJ9-1 (white solid, 24.8 mg, 57%).

[2757] LCMS: m/z 417 [M+H].sup.+

[2758] HPLC retention time: 2.81 min (analysis condition F)

Example 463

Compound JJ9-3

9-((S)-2,2-Dimethyl-[1,3]dioxolan-4-yl methoxy)-5,6,6-trimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2759] ##STR00478##

[2760] Under the same conditions as the method for synthesizing Compound JJ4-1, the title compound was prepared from 9-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (Compound JJ9-2) (17.0 mg, 84%).

[2761] LCMS: m/z 431 [M+H].sup.+

[2762] HPLC retention time: 3.00 min (analysis condition F)

Example 464

Compound JJ9-4

9-((R)-2,3-Dihydroxy-propoxy)-5,6,6-trimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2763] ##STR00479##

[2764] Under the same conditions as the method for synthesizing Compound JJ3-2, the title compound was prepared from 9-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy)-5,6,6-trimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (JJ9-3) (white solid, 12.1 mg, 90%).

[2765] LCMS: m/z 391 [M+H].sup.+

[2766] HPLC retention time: 2.13 min (analysis condition F)

Example 465

Compound JJ10-1

9-Benzyloxy-3-bromo-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one

[2767] ##STR00480##

[2768] Under the same conditions as the method for synthesizing Compound A7-17, the title compound was prepared from Compound JJ2 and benzyl bromide (18.2 mg, 61%).

[2769] LCMS: m/z 446 [M+H].sup.+

[2770] HPLC retention time: 2.68 min (analysis condition D)

Example 466

Compound JJ10-2

5-Benzyl-9-benzyloxy-3-bromo-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one

[2771] ##STR00481##

[2772] The title compound was obtained as a by-product of the synthesis of Compound JJ10-1 (5.3 mg, 21%).

[2773] LCMS: m/z 536 [M+H].sup.+

[2774] HPLC retention time: 3.17 min (analysis condition D)

Example 467

Compound JJ10-3

3-Bromo-9-(4-methoxy-benzyloxy)-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one

[2775] ##STR00482##

[2776] Under the same conditions as the method for synthesizing Compound A7-1, the title compound was prepared by reacting Compound JJ2 and (4-methoxyphenyl)-methanol (7.5 mg, 28%).

[2777] LCMS: m/z 476 [M+H].sup.+

[2778] HPLC retention time: 2.70 min (analysis condition D)

Example 468

Compound K2

2-(3-Bromo-4-methoxy-phenyl)-2-methyl-propionitrile

[2779] ##STR00483##

[2780] To the THF suspension of potassium tert-butoxide (15.35 g, 3 eq.), (3-bromo-4-methoxyphenyl)acetonitrile (Compound K1, 10 g, 0.044 mmol) was added, and then stirred at 0 C. for 1 hr. Then, iodomethane (8.26 ml, 3 eq.) was added and the mixture was stirred at room temperature for 1 hr. To the reaction solution, saturated aqueous solution of ammonium chloride and water were added followed by extraction with ethyl acetate. The organic layer was washed with brine and dried over sodium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain the title compound (colorless oily substance, 11.24 g, 100%).

[2781] .sup.1H-NMR (270 MHz, DMSO-d.sub.6) : 7.69 (1H, d, J=2.5 Hz), 7.50 (1H, dd, J=8.6, 2.5 Hz), 7.16 (1H, d, J=8.6 Hz), 3.86 (3H, s), 1.67 (6H, s).

[2782] HPLC retention time: 2.30 min (analysis condition S)

Example 469

Compound K3

4-(3-Bromo-4-methoxy-phenyl)-4-methyl-3-oxo-pentanoic acid ethyl ester

[2783] ##STR00484##

[2784] To the THF suspension of zinc (5.72 g, 2 eq.), methanesulfonic acid (25.6 l, 0.01 eq.) was added, and then stirred at 80 C. for 10 min. Then, the THF solution of 2-(3-bromo-4-methoxy-phenyl)-2-methyl-propionitrile (10 g, 39.35 mmol) was added, followed by addition of bromoethyl acetate (11.07 ml, 1.6 eq.) over 1 hr. The mixture was further stirred for 30 min. To the reaction solution, 4 M hydrochloric acid was added, and stirred at room temperature overnight. After extraction with ethyl acetate, the organic layer was washed with brine and dried over sodium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain the title compound (orange oily substance, 9.74 g, 72%).

[2785] .sup.1H-NMR (270 MHz, CDCl.sub.3) : 7.46 (1H, d, J=2.5 Hz), 7.16 (1H, dd, J=8.6, 2.5 Hz), 6.89 (1H, d, J=8.6 Hz), 4.17-4.08 (2H, m), 3.90 (3H, s), 3.26 (2H, s), 1.49 (6H, s), 1.23 (3H, t, J=7.2 Hz).

[2786] LCMS: m/z 343, 345 [M+H].sup.+

[2787] HPLC retention time: 2.64 min (analysis condition S)

Example 470

Compound K4

4-(3-Bromo-4-methoxy-phenyl)-2-(4-cyano-2-nitro-phenyl)-4-methyl-3-oxo-pentanoic Acid Ethyl Ester

[2788] ##STR00485##

[2789] 4-(3-Bromo-4-methoxy-phenyl)-4-methyl-3-oxo-pentanoic acid ethyl ester (Compound K3, 10.3 g, 30.01 mmol) was dissolved in DMF (80 mL), added with cesium carbonate (24.4 g, 2.5 eq.) and 4-chloro-3-nitro-benzonitrile (7.12 g, 1.3 eq.), and then stirred at 45 C. for 4 hr. The reaction solution was added to 1 N aqueous solution of hydrochloric acid, and extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over sodium sulfate. The drying agent was removed by filtration, and after concentration under reduced pressure the title compound was obtained as a crude product (yellow oily substance).

[2790] LCMS: m/z 489, 491 [M+H].sup.+

[2791] HPLC retention time: 2.85, 3.20 min (analysis condition S)

Example 471

Compound K5

2-[1-(3-Bromo-4-methoxy-phenyl)-1-methyl-ethyl]-6-cyano-1H-indole-3-carboxylic Acid Ethyl Ester

[2792] ##STR00486##

[2793] 4-(3-Bromo-4-methoxy-phenyl)-2-(4-cyano-2-nitro-phenyl)-4-methyl-3-oxo-pentanoic acid ethyl ester (Compound K4), which had been obtained from the above, was dissolved in THF (140 mL) and water (70 mL), added with Na.sub.2S.sub.2O.sub.4 (26.13 g, 5.0 eq.) and stirred at 50 C. overnight. The reaction solution was added to saturated brine and extracted with ethyl acetate. The organic layer was washed with 1 M aqueous solution of potassium carbonate and saturated brine in order, and dried over sodium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were purified by crystallization in MeCN (80 ml) to obtain the title compound (yellow solid, 8.20 g, 62%).

[2794] .sup.1H-NMR (270 MHz, DMSO-d.sub.6) : 12.15 (1H, s), 8.07 (1H, d, J=8.4 Hz), 7.94 (1H, s), 7.51 (1H, dd, J=8.5, 1.2 Hz), 7.33 (1H, d, J=2.1 Hz), 7.03 (1H, dd, J=8.7, 2.4 Hz), 6.96 (1H, d, J=8.4 Hz), 3.97 (2H, q, J=7.3 Hz), 3.78 (3H, s), 1.80 (6H, s), 1.09 (3H, t, J=7.2 Hz).

[2795] LCMS: m/z 441, 443 [M+H].sup.+

[2796] HPLC retention time: 2.85 min (analysis condition S)

Example 472

Compound K6

8-Bromo-9-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2797] ##STR00487##

[2798] Phosphorus pentoxide-methanesulfonic acid (12 mL) was added with 2-[1-(3-bromo-4-methoxy-phenyl)-1-methyl-ethyl]-6-cyano-1H-indole-3-carboxylic acid ethyl ester (Compound K5, 1.0 g, 2.27 mmol), and the mixture was stirred at room temperature for 20 min. The reaction solution was diluted with MeCN (20 mL), poured into water (20 mL), and the precipitated solid was filtered to obtain the title compound (yellow solid, 763 mg, 85%).

[2799] .sup.1H-NMR (270 MHz, DMSO-d.sub.6) : 12.84 (1H, s), 8.32 (1H, d, J=8.1 Hz), 8.15 (1H, s), 8.03 (1H, s), 7.77 (1H, s), 7.64 (1H, dd, J=8.2, 1.4 Hz), 3.97 (3H, s), 1.75 (6H, s).

[2800] LCMS: m/z 395, 397 [M+H].sup.+

[2801] HPLC retention time: 2.58 min (analysis condition S)

Example 473

Compound K7-1

9-Methoxy-6,6-dimethyl-11-oxo-8-(4-pyrrolidin-1-yl-piperidin-1-yl)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2802] ##STR00488##

[2803] Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound K6 and 4-pyrrolidin-1-yl-piperidine.

[2804] LCMS: m/z 469 [M+H].sup.+

[2805] HPLC retention time: 1.37 min (analysis condition S)

Example 474

Compound K7-2

9-Methoxy-6,6-dimethyl-8-(4-morpholin-1-yl-piperidin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2806] ##STR00489##

[2807] Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound K6 and 4-piperidin-4-yl-morpholine.

[2808] .sup.1H-NMR (270 MHz, DMSO-d.sub.6) : 12.70 (1H, s), 8.31 (1H, d, J=8.2 Hz), 7.99 (1H, s), 7.63 (1H, s), 7.60 (1H, dd, J=8.2, 1.2 Hz), 7.16 (1H, s), 3.89 (3H, s), 3.64 (2H, brd), 2.72 (2H, brd), 1.91 (2H, brd), 1.73 (6H, s), 1.57 (2H, brd).

[2809] LCMS: m/z 485 [M+H].sup.+

[2810] HPLC retention time: 1.33 min (analysis condition S)

Example 475

Compound K7-3

9-Methoxy-6,6-dimethyl-11-oxo-8-piperazin-1-yl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2811] ##STR00490##

[2812] Under the same conditions as the method for synthesizing Compound B2-1, the target compound was prepared from Compound K6 and piperazine.

[2813] LCMS: m/z 401 [M+H].sup.+

[2814] HPLC retention time: 1.31 min (analysis condition S)

Example 476

Compound K7-4

9-Methoxy-6,6-dimethyl-8-morpholin-4-yl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2815] ##STR00491##

[2816] Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound K6 and morpholine.

[2817] LCMS: m/z 402 [M+H].sup.+

[2818] HPLC retention time: 2.10 min (analysis condition S)

Example 477

Compound K8

8-(4-Cyclobutyl-piperazin-1-yl)-9-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2819] ##STR00492##

[2820] Under the same conditions as the method for synthesizing Compound B3-32, the title compound was prepared from Compound K7-3 and cyclobutanone.

[2821] .sup.1H-NMR (270 MHz, DMSO-d.sub.6) : 12.70 (1H, br. s), 8.31 (1H, d, J=8.2 Hz), 8.00 (1H, s), 7.64 (1H, s), 7.61 (1H, dd, J=8.1, 1.3 Hz), 7.16 (1H, s), 3.88 (3H, s), 3.60 (1H, t, J=6.2 Hz), 3.10-3.25 (4H, m), 2.77 (1H, t, J=7.1 Hz), 2.35-2.51 (4H, m), 1.74 (6H, s), 1.58-2.08 (6H, m).

[2822] LCMS: m/z 455 [M+H].sup.+

[2823] HPLC retention time: 1.45 min (analysis condition S)

Example 478

Compound K9-1

9-Hydroxy-6,6-dimethyl-11-oxo-8-(4-pyrrolidin-1-yl-piperidin-1-yl)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2824] ##STR00493##

[2825] The title compound was obtained as a by-product of the synthesis of Compound K7-1.

[2826] LCMS: m/z 455 [M+H].sup.+

[2827] HPLC retention time: 1.22 min (analysis condition S)

Example 479

Compound K9-2

9-Hydroxy-6,6-dimethyl-8-(4-morpholin-4-yl-piperidin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2828] ##STR00494##

[2829] Under the same conditions as the method for synthesizing Compound E3-2, the title compound was prepared from Compound K7-2.

[2830] .sup.1H-NMR (270 MHz, DMSO-d.sub.6) : 12.65 (1H, s), 9.61 (1H, s), 8.30 (1H, d, J=8.2 Hz), 7.98 (1H, s), 7.59-7.56 (2H, m), 7.10 (1H, s), 3.71 (2H, brd, J=11.2 Hz), 3.60 (4H, m), 2.66 (2H, m), 1.88 (2H, brd, J=9.7 Hz), 1.71 (6H, s), 1.57 (2H, brd).

[2831] LCMS: m/z 471 [M+H].sup.+

[2832] HPLC retention time: 1.20 min (analysis condition S)

Example 480

Compound K9-3

8-(4-Cyclobutyl-piperazin-1-yl)-9-hydroxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2833] ##STR00495##

[2834] Under the same conditions as the method for synthesizing Compound E3-2, the title compound was prepared from Compound K8.

[2835] .sup.1H-NMR (270 MHz, DMSO-d.sub.6) : 12.66 (1H, br. s), 9.67 (1H, s), 8.31 (1H, d, J=8.2 Hz), 7.98 (1H, s), 7.56-7.60 (2H, m), 7.09 (1H, s), 3.10-3.24 (4H, m), 2.77 (1H, t, J=7.5 Hz), 2.37-2.49 (4H, m), 1.52-2.07 (6H, m), 1.72 (6H, s).

[2836] LCMS: m/z 441 [M+H].sup.+

[2837] HPLC retention time: 1.31 min (analysis condition S)

Example 481

Compound K9-4

9-Hydroxy-6,6-dimethyl-8-morpholin-4-yl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2838] ##STR00496##

[2839] Under the same conditions as the method for synthesizing Compound E3-2, the title compound was prepared from Compound K7-4.

[2840] LCMS: m/z 388 [M+H].sup.+

[2841] HPLC retention time: 1.67 min (analysis condition S)

Example 482

Compound K10-1

9-Isopropoxy-6,6-dimethyl-8-(4-morpholin-4-yl-piperidin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2842] ##STR00497##

[2843] Under the same conditions as the method for synthesizing Compound A7-17, the title compound was prepared from Compound K9-2 and 2-bromopropane.

[2844] .sup.1H-NMR (270 MHz, DMSO-d.sub.6) : 12.68 (1H, s), 8.30 (1H, d, J=8.1 Hz), 7.99 (1H, s), 7.60 (2H, m), 7.14 (1H, s), 4.72-4.63 (2H, m), 3.71 (2H, brd, J=10.7 Hz), 3.59 (6H, m), 2.68 (2H, t, J=12.9 Hz), 2.27 (2H, brd), 1.90 (2H, brd), 1.73 (6H, s), 1.56 (2H, br), 1.34 (6H, d, J=5.9 Hz).

[2845] LCMS: m/z 513 [M+H].sup.+

[2846] HPLC retention time: 1.48 min (analysis condition S)

Example 483

Compound K10-2

8-(4-Cyclobutyl-piperazin-1-yl)-9-isopropoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2847] ##STR00498##

[2848] Under the same conditions as the method for synthesizing Compound A7-17, the title compound was prepared from Compound K9-3 and 2-iodopropane.

[2849] .sup.1H-NMR (270 MHz, DMSO-d.sub.6) : 8.29 (1H, d, J=8.1 Hz), 7.98 (1H, s), 7.56-7.63 (2H, m), 7.14 (1H, s), 4.62-4.74 (1H, m), 3.10-3.26 (4H, m), 2.69-2.85 (1H, m), 2.35-2.48 (4H, m), 1.57-2.08 (6H, m), 1.73 (6H, s), 1.32 (6H, d, J=6.1 Hz).

[2850] LCMS: m/z 483 [M+H].sup.+

[2851] HPLC retention time: 1.65 min (analysis condition S)

Example 484

Compound K10-3

9-(2-Methoxy-ethoxy)-6,6-dimethyl-8-morpholin-4-yl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2852] ##STR00499##

[2853] Under the same conditions as the method for synthesizing Compound A7-17, the title compound was prepared from Compound K9-4 and 1-bromo-2-methoxyethane.

[2854] .sup.1H-NMR (400 MHz, DMSO-d.sub.6) : 12.67 (1H, s), 8.30 (1H, d, 7.9 Hz), 7.98 (1H, s), 7.64 (1, s), 7.58 (1H, d, 7.9 Hz), 7.16 (1H, s), 4.18-4.22 (2H, m), 3.72-3.80 (6H, m), 3.35 (3H, s), 3.18-3.24 (4H, s), 1.74 (1H, s)

[2855] LCMS: m/z 446 [M+H].sup.+

[2856] HPLC retention time: 3.23 min (analysis condition W)

Example 485

Compound K10-4

9-[2-(2-Methoxy-ethoxy)-ethoxy]-6,6-dimethyl-8-morpholin-4-yl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2857] ##STR00500##

[2858] Under the same conditions as the method for synthesizing Compound A7-17, the title compound was prepared from Compound K9-4 and 1-bromo-2-(2-methoxyethoxy)ethane.

[2859] LCMS: m/z 490 [M+H].sup.+

[2860] HPLC retention time: 3.16 min (analysis condition W)

Example 486

Compound K10-5

6,6-Dimethyl-8-morpholin-1-yl-11-oxo-9-[(S)-(tetrahydro-furan-3-yl)oxy]-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2861] ##STR00501##

[2862] Under the same conditions as the method for synthesizing Compound A7-17, the title compound was prepared from Compound K9-4 and 3-mesyloxytetrahydrofurane.

[2863] LCMS: m/z 458 [M+H].sup.+

[2864] HPLC retention time: 3.20 min (analysis condition W)

Example 487

Compound K10-6

9-Isopropoxy-6,6-dimethyl-8-morpholin-4-yl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2865] ##STR00502##

[2866] Under the same conditions as the method for synthesizing Compound A7-17, the title compound was prepared from Compound K9-4 and 2-bromopropane.

[2867] .sup.1H-NMR (270 MHz, DMSO-d.sub.6) : 12.70 (1H, br. s), 8.32-8.29 (1H, d, 8.08 Hz), 8.00 (1H, s), 7.63 (1H, s), 7.62-7.59 (1H, d, 8.08 Hz), 7.16 (1H, s), 4.75-4.66 (1H, m), 3.77 (4H, m) 3.19 (4H, m), 1.74 (6H, s), 1.35 (3H, s), 1.33 (3H, s)

[2868] LCMS: m/z 430 [M+H].sup.+

Example 488

Compound K10-7

9-(2-Hydroxy-ethoxy)-6,6-dimethyl-8-morpholin-4-yl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2869] ##STR00503##

[2870] Under the same conditions as the method for synthesizing Compound A7-17, the title compound was prepared from Compound K9-4 and 2-bromoethanol.

[2871] .sup.1H-NMR (270 MHz, DMSO-d.sub.6) : 12.71 (1H, br. s), 8.33-8.30 (1H, d, 8.08 Hz), 8.00 (1H, s), 7.63 (1H, s), 7.62-7.59 (1H, d, 8.08 Hz), 7.16 (1H, s), 4.13-4.09 (2H, t, 4.61 Hz), 3.81-3.78 (2H, t, 4.61 Hz), 3.78 (4H, m) 3.23 (4H, m), 1.75 (6H, s)

[2872] LCMS: m/z 432 [M+H].sup.+

Example 489

Compound L2-1

(4-Isopropoxy-3-methoxy-phenyl)-ethyl Acetate Ester

[2873] ##STR00504##

[2874] (4-Hydroxy-3-methoxy-phenyl)-ethyl acetate ester (Compound L1-1, 3.0 g, 14.27 mmol) was dissolved in DMF (70 mL), added with 2-iodopropane (2.9 mL, 2.0 eq.) and potassium carbonate (3.94 g, 2.0 eq.), and stirred at 80 C. overnight. The reaction solution was added to water and extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over sodium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain the target compound (yellow oily substance, 2.61 g, 73%).

[2875] .sup.1H-NMR (270 MHz, DMSO-d.sub.6) : 6.88 (2H, m), 6.74 (1H, dd, J=8.1, 2.1 Hz), 4.52-4.43 (1H, m), 4.07 (2H, q, J=7.1 Hz), 3.72 (3H, s), 3.56 (2H, s), 1.23 (6H, d, J=6.1 Hz), 1.18 (3H, t, J=7.1 Hz).

[2876] LCMS: m/z 253 [M+H].sup.+

[2877] HPLC retention time: 2.18 min (analysis condition S)

Example 490

Compound L2-2

(4-Isopropoxy-3-methoxy-phenyl)-acetic Acid Isopropyl Ester

[2878] ##STR00505##

[2879] (4-Hydroxy-3-methoxy-phenyl)-acetic acid (Compound L1-2, 1.5 g, 8.23 mmol) was dissolved in DMF (30 mL), added with 2-iodopropane (3.3 mL, 4.0 eq.) and potassium carbonate (4.55 g, 4.0 eq.), and stirred at 80 C. overnight. The reaction solution was added to water and extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over sodium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain the target compound (yellow oily substance, 1.21 g, 55%).

[2880] .sup.1H-NMR (270 MHz, DMSO-d.sub.6) : 6.87 (2H, s+d), 6.73 (1H, dd, J=8.1, 2.1 Hz), 4.94-4.84 (1H, m), 4.52-4.43 (1H, m), 3.72 (3H, s), 3.52 (2H, s), 1.23 (6H, d, J=6.1 Hz), 1.18 (6H, d, J=6.1 Hz).

[2881] LCMS: m/z 267 [M+H].sup.+

[2882] HPLC retention time: 2.40 min (analysis condition S)

Example 491

Compound L3-1

2-(4-Isopropoxy-3-methoxy-phenyl)-2-methyl-propionic Acid Ethyl Ester

[2883] ##STR00506##

[2884] Under the same conditions as the method for synthesizing Compound K2, the title compound was prepared from Compound L2-1.

[2885] .sup.1H-NMR (270 MHz, DMSO-d.sub.6) : 6.90-6.76 (3H, m), 4.53-4.44 (1H, m), 4.06 (2H, q, J=7.1 Hz), 3.73 (3H, s), 1.47 (6H, s), 1.23 (6H, d, J=6.1 Hz), 1.12 (3H, t, J=7.0 Hz).

[2886] LCMS: m/z 281 [M+H].sup.+

[2887] HPLC retention time: 2.57 min (analysis condition S)

Example 492

Compound L3-2

2-(4-Isopropoxy-3-methoxy-phenyl)-2-methyl-propionic Acid Isopropyl Ester

[2888] ##STR00507##

[2889] Under the same conditions as the method for synthesizing Compound K2, the title compound was prepared from Compound L2-2.

[2890] .sup.1H-NMR (270 MHz, DMSO-d.sub.6) : 6.88 (1H, d, J=8.2 Hz), 6.79 (2H, m), 4. 94-4.84 (1H, m), 4.53-4.44 (1H, m), 3.72 (3H, s), 1.45 (6H, s), 1.23 (6H, d, J=6.1 Hz), 1.12 (6H, d, J=6.3 Hz).

[2891] LCMS: m/z 295 [M+H].sup.+

[2892] HPLC retention time: 2.75 min (analysis condition S)

Example 493

Compound L4

2-(4-Isopropoxy-3-methoxy-phenyl)-2-methyl-propionic Acid

[2893] ##STR00508##

[2894] 2-(4-Isopropoxy-3-methoxy-phenyl)-2-methyl-propionic acid ethyl ester (Compound L3-1, 1.45 g, 5.17 mmol) was dissolved in THF (13 mL) and EtOH (13 mL), added with 1 N aqueous solution of sodium hydroxide (10.3 mL, 2.0 eq.), and stirred at 80 C. overnight. The reaction solution was added to water and extracted with ethyl acetate. The aqueous layer was acidified by using 1 N aqueous solution of hydrochloric acid, extracted with ethyl acetate, washed with saturated brine and dried over sodium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain the target compound (white solid, 1.10 g, 84%).

[2895] .sup.1H-NMR (270 MHz, DMSO-d.sub.6) : 12.26 (1H, s), 6.90-6.80 (3H, m), 4.49 (1H, m), 3.73 (3H, s), 1.45 (6H, s), 1.23 (6H, d, J=6.1 Hz).

[2896] LCMS: m/z 253 [M+H].sup.+

[2897] HPLC retention time: 1.83 min (analysis condition S)

Example 494

Compound L5

4-(4-Isopropoxy-3-methoxy-phenyl)-4-methyl-3-oxo-pentanoic Acid Ethyl Ester

[2898] ##STR00509##

[2899] 2-(4-Isopropoxy-3-methoxy-phenyl)-2-methyl-propionic acid (Compound L4, 1.4 g, 5.55 mmol) was added with thionyl chloride (10 mL), and then stirred at room temperature for 5 hr. According to the concentration under reduced pressure, unreacted thionyl chloride was removed to obtain corresponding acid chloride.

[2900] To MeCN (40 mL), malonic acid monoethyl ester potassium salt (1.98 g, 2.1 eq.), triethylamine (2.47 mL, 3.2 eq.), and magnesium chloride (1.32 g, 2.5 eq.) were added and the mixture was stirred at room temperature for 2 hr. To the reaction solution, MeCN (15 mL) solution of the acid chloride prepared from the above was added dropwise. Upon the completion of the dropwise addition, the mixture was further stirred at room temperature for overnight. MeCN was removed by distillation and concentrated under reduced pressure, and the resulting residues were added with 1 N aqueous solution of hydrochloric acid, extracted with toluene, washed with saturated brine, and dried over sodium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain the target compound (yellow oily substance, 1.45 g, 81%).

[2901] .sup.1H-NMR (270 MHz, DMSO-d.sub.6) : 6.94 (1H, d, J=8.2 Hz), 6.76 (2H, m), 4.56-4.47 (1H, m), 4.00 (2H, q, J=7.1 Hz), 3.74 (3H, s), 3.38 (2H, s), 1.41 (6H, s), 1.24 (6H, d, J=6.1 Hz), 1.12 (3H, t, J=7.3 Hz).

[2902] LCMS: m/z 323 [M+H].sup.+

[2903] HPLC retention time: 2.45, 3.03 min (analysis condition S)

Example 495

Compound L6

2-(4-Cyano-2-nitro-phenyl)-4-(4-isopropoxy-3-methoxy-phenyl)-4-methyl-3-oxo-pentanoic Acid Ethyl Ester

[2904] ##STR00510##

[2905] Under the same conditions as the method for synthesizing Compound K4, the title compound was prepared from Compound L5.

[2906] .sup.1H-NMR (270 MHz, DMSO-d.sub.6) : 8.35 (1H, d, J=1.8 Hz), 8.14 (1H, dd, J=8.2, 1.9 Hz), 7.67 (1H, d, J=8.2 Hz), 6.68 (1H, d, J=8.4 Hz), 6.59 (1H, dd, J=8.4, 2.0 Hz), 6.45 (1H, d, J=2.1 Hz), 5.44 (1H, s), 4.43 (1H, m), 4.09 (2H, q, J=7.1 Hz), 3.53 (3H, s), 1.59 (3H, s), 1.35 (3H, s), 1.24 (6H, dx2), 1.13 (3H, t, J=7.1 Hz).

[2907] LCMS: m/z 469 [M+H].sup.+

[2908] HPLC retention time: 2.85, 3.10 min (analysis condition S)

Example 496

Compound L7

6-Cyano-2-[1-(4-isopropoxy-3-methoxy-phenyl)-1-methyl-ethyl]-1H-indole-3-carboxylic Acid Ethyl Ester

[2909] ##STR00511##

[2910] Under the same conditions as the method for synthesizing Compound K5, the title compound was prepared from Compound L6.

[2911] .sup.1H-NMR (270 MHz, DMSO-d.sub.6) : 12.04 (1H, s), 8.05 (1H, d, J=8.4 Hz), 7.93 (1H, s), 7.49 (1H, dd, J=8.4, 1.5 Hz), 6.79 (2H, m), 6.54 (1H, dd, J=8.3, 1.9 Hz), 4.43 (1H, t, J=6.1 Hz), 3.94 (2H, q, J=7.0 Hz), 3.65 (3H, s), 1.81 (6H, s), 1.21 (6H, d, J=5.9 Hz), 1.05 (3H, t, J=7.1 Hz).

[2912] LCMS: m/z 421 [M+H].sup.+

[2913] HPLC retention time: 2.82 min (analysis condition S)

Example 497

Compound L8-1

9-Hydroxy-8-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2914] ##STR00512##

[2915] 6-Cyano-2-[1-(4-isopropoxy-3-methoxy-phenyl)-1-methyl-ethyl]-1H-indole-3-carboxylic acid ethyl ester (Compound L7, 1.25 g, 2.97 mmol) was dissolved in MeCN (18 mL), added with methanesulfonic acid (3.75 mL), and then stirred at 50 C. for 8 hr. Hexane was added to the reaction solution, and the precipitated solid was filtered to obtain the title compound (yellow solid, 185 mg, 19%).

[2916] .sup.1H-NMR (270 MHz, DMSO-d.sub.6) : 12.67 (1H, s), 8.30 (1H, d, J=8.2 Hz), 7.99 (1H, s), 7.59 (2H, m), 7.28 (1H, s), 3.93 (3H, s), 1.75 (6H, s).

[2917] LCMS: m/z 333 [M+H].sup.+

[2918] HPLC retention time: 1.73 min (analysis condition S)

Example 498

Compound L8-2

9-Isopropoxy-8-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2919] ##STR00513##

[2920] To the filtrate obtained from the synthesis of Compound L8-1, water was added and the extraction was carried out with ethyl acetate. The resultant was washed with saturated brine and dried over sodium sulfate. The drying agent was removed by filtration and the concentration was performed under reduced pressure to obtain the target compound (red amorphous, 830 mg, 75%).

[2921] .sup.1H-NMR (270 MHz, DMSO-d.sub.6) : 12.72 (1H, s), 8.31 (1H, d, J=8.4 Hz), 8.01 (1H, d, J=0.7 Hz), 7.66 (1H, s), 7.61 (1H, dd, J=8.2, 1.4 Hz), 7.33 (1H, s), 4.65 (1H, m), 3.93 (3H, s), 1.77 (6H, s), 1.32 (6H, d, J=6.1 Hz).

[2922] LCMS: m/z 375 [M+H].sup.+

[2923] HPLC retention time: 2.38 min (analysis condition S)

Example 499

Compound L9

8-Hydroxy-9-isopropoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2924] ##STR00514##

[2925] Under the same conditions as the method for synthesizing Compound E3-2, the title compound was prepared from Compound L8-2.

[2926] .sup.1H-NMR (270 MHz, DMSO-d.sub.6) : 12.69 (1H, s), 9.69 (1H, s), 8.30 (1H, d, J=8.1 Hz), 7.99 (1H, s), 7.65 (1H, s), 7.60 (1H, dd, J=8.2, 1.2 Hz), 7.17 (1H, s), 4.64 (1H, m), 1.69 (6H, s), 1.32 (6H, d, J=6.1 Hz).

[2927] LCMS: m/z 361 [M+H].sup.+

[2928] HPLC retention time: 2.20 min (analysis condition S)

Example 500

Compound L10-1

8-(1-Cyclobutyl-piperidin-4-yloxy)-9-isopropoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2929] ##STR00515##

[2930] Under the same conditions as the method for synthesizing Compound A7-1, the title compound was prepared from Compound L9 and 1-cyclobutylpiperidin-4-ol.

[2931] .sup.1H-NMR (270 MHz, CDCl.sub.3) : 9.31 (1H, br. s), 8.54-8.50 (1H, d, 8.08 Hz), 7.90 (1H, s), 7.77 (1H, s), 7.59-7.55 (1H, m), 7.09 (1H, s), 4.70-4.61 (1H, m), 4.52-4.43 (1H, m), 2.79-2.73 (1H, m), 2.70-2.60 (2H, m), 2.25-2.16 (2H, m), 2.09-1.99 (4H, m), 1.98-1.88 (4H, m), 1.77 (6H, s), 1.72-1.58 (2H, m), 1.39 (3H, s), 1.37 (3H, s)

[2932] LCMS: m/z 498 [M+H].sup.+

Example 501

Compound L10-2

8-((R)-1-Cyclobutyl-pyrrolidin-3-yl oxy)-9-isopropoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[2933] ##STR00516##

[2934] Under the same conditions as the method for synthesizing Compound A7-1, the title compound was prepared from Compound L9 and (S)-1-cyclobutylpyrrolidin-3-ol.

[2935] .sup.1H-NMR (270 MHz, CDCl.sub.3) : 10.63 (1H, br. s), 8.51-8.48 (1H, d, 8.08 Hz), 7.89 (1H, s), 7.85 (1H, s), 7.55-7.51 (1H, m), 6.99 (1H, s), 5.03-4.97 (1H, m), 4.71-4.62 (1H, m), 3.07-292 (2H, m), 2.84-2.73 (2H, m), 2.64-2.53 (1H, m), 2.36-2.23 (2H, m), 2.10-1.97 (2H, m), 1.83-1.67 (2H, m), 1.78 (6H, s), 1.53-1.46 (2H, m), 1.39 (3H, s), 1.37 (3H, s)

[2936] LCMS: m/z 484 [M+H].sup.+

Example 502

Compound M1

7-Methoxy-3,4-dihydro-2H-spiro[cyclopentane-1,1-naphthalen]-2-one

[2937] ##STR00517##

[2938] To the THF (300 ml) solution of 7-methoxy-3,4-dihydro-1H-naphthalen-2-one (Compound A1, 0.5 g, 2.84 mmol), sodium hydride (36.4 mg, 2.2 eq.) was added at 0 C. After stirring for 20 min, 1,4-dibromobutane (0.74 ml, 1.2 eq.) was added dropwise thereto, and the mixture was stirred at 80 C. for 4 hr. To the reaction solution, saturated aqueous solution of ammonium chloride was added followed by extraction with ethyl acetate. The organic layer was washed with saturated aqueous solution of ammonium chloride and dried over magnesium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain the title compound (yellow solid, 0.31 g, 47%).

[2939] .sup.1H-NMR (CDCl.sub.3, 300 MHz): 1.79-1.92 (6H, m), 2.42-2.27 (m, 2H), 3.03 (t, 2H, J=6.5 Hz), 3.81 (t, 2H, J=6.5 Hz), 3.81 (s, 3H), 6.73 (dd, 1H, J=2.7 Hz, 8.0 Hz), 6.83 (d, 1H, J=2.7 Hz), 7.09 (d, 1H, J=8.0 Hz)

[2940] LCMS: m/z 231 [M+H].sup.+

Example 503

Compound M2

3-Bromo-8-methoxy-5,11-dihydrospiro[benzo[b]carbazole-6,1-cyclopentane]

[2941] ##STR00518##

[2942] Under the same conditions as the method for synthesizing Compound A3-1, the title compound was prepared from Compound M1 and (3-bromo-phenyl)-hydrazine.

[2943] LCMS: m/z 380, 382 [M+H].sup.+

[2944] HPLC retention time: 2.90 min (analysis condition Y)

Example 504

Compound M3

3-Bromo-8-methoxyspiro[benzo[b]carbazole-6,1-cyclopentan]-11(5H)-one

[2945] ##STR00519##

[2946] Under the same conditions as the method for synthesizing Compound A4, the title compound was prepared from Compound M2.

[2947] .sup.1H-NMR (CDCl.sub.3, 300 MHz) : 2.11-2.51 (8H, m), 3.91 (s, 3H), 6.98 (dd, 1H, J=2.3 Hz, 8.8 Hz), 7.01 (d, 1H, J=2.3 Hz), 7.41 (dd, 1H, J=1.5 Hz, 8.4 Hz), 7.57 (d, 1H, J=1.5 Hz), 8.30 (d, 1H, J=8.4 Hz), 8.35 (d, 1H, J=8.8 Hz), 8.69 (s, 1H)

[2948] LCMS: m/z 396, 398 [M+H].sup.+

Example 505

Compound M4

8-Methoxy-11-oxo-5,11-dihydrospiro[benzo[b]carbazole-6,1-cyclopentane]-3-carbonitrile

[2949] ##STR00520##

[2950] Under the same conditions as the method for synthesizing Compound A5-2, the title compound was prepared from Compound M3.

[2951] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) : 2.14-2.37 (m, 8H), 3.90 (s, 3H), 7.05-7.10 (m, 2H), 7.60 (dd, 1H, J=1.5 Hz, 8.4 Hz), 7.95 (s, 1H), 8.13 (d, 1H, J=9.5 Hz), 8.30 (d, 1H, J=8.4 Hz), 12.24 (s, 1H)

[2952] LCMS: m/z 343 [M+H].sup.+

Example 506

Compound M5

8-Hydroxy-11-oxo-5,11-dihydrospiro[benzo[b]carbazole-6,1-cyclopentane]-3-carbonitrile

[2953] ##STR00521##

[2954] Under the same conditions as the method for synthesizing Compound A6, the title compound was prepared from Compound M4.

[2955] .sup.1H-NMR (DMSO-d.sub.6, 300 MHz) : 2.06-2.39 (m, 8H), 6.87 (dd, 1H, J=1.9 Hz, 8.8 Hz), 6.90 (d, 1H, J=1.9 Hz), 7.57 (dd, 1H, J=1.1 Hz, 8.0 Hz), 7.95 (s, 1H), 8.02 (d, 1H, J=8.8 Hz), 8.30 (d, 1H, J=8.0 Hz), 10.29 (s, 1H), 12.25 (s, 1H)

[2956] LCMS: m/z 329 [M+H].sup.+

Example 507

Compound M6-1

(S)-8-((2,2-Dimethyl-1,3-dioxolan-4-yl)methoxy)-11-oxo-5,11-dihydrospiro[benzo[b]carbazole-6,1-cyclopentane]-3-carbonitrile

[2957] ##STR00522##

[2958] Under the same conditions as the method for synthesizing Compound A7-17, the title compound was prepared as a crude product from Compound M5 and toluene-4-sulfonic acid(R)-2,2-dimethyl-[1,3]dioxolan-4-yl methyl ester.

Example 508

Compound M6-2

(R)-8-(2,3-Dihydroxypropoxy)-11-oxo-5,11-dihydrospiro[benzo[b]carbazole-6,1-cyclopentane]-3-carbonitrile

[2959] ##STR00523##

[2960] Under the same conditions as the method for synthesizing Compound A7-14-2, the title compound was prepared from Compound M6-1.

[2961] LCMS: m/z 403 [M+H].sup.+

[2962] HPLC retention time: 2.88 min (analysis condition U)

Example 509

Compound N1

7-Methoxy-2,3,3,4,5,6-hexahydro-2H-spiro[naphthalene-1,4-pyran]-2-one

[2963] ##STR00524##

[2964] To the THF (300 ml) solution of 7-methoxy-3,4-dihydro-1H-naphthalen-2-one (Compound A1, 20 g, 0.11 mol), sodium hydride (9.9 g, 3.7 eq.) was added at 0 C. After stirring for 10 min, 1-bromo-2-(2-bromo-ethoxy)-ethane (19 ml, 12 eq.) was added dropwise thereto, and the mixture was stirred at 80 C. for 3 hr. To the reaction solution, saturated aqueous solution of ammonium chloride was added and the extraction was carried out twice with ethyl acetate. The organic layer was dried over magnesium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain the title compound (white solid, 13 g, 51%).

[2965] .sup.1H-NMR (300 MHz, CDCl.sub.3) : 2.07 (4H, m), 2.70 (t, 2H, 6.8 Hz), 3.12 (t, 2H, 6.8 Hz), 3.81 (s, 3H), 3.89 (m, 4H), 6.75 (dd, 1H, 2.6 Hz, 8.3 Hz), 6.9 (d, 1H, 2.6 Hz), 7.0 (d, 1H, 8.3 Hz)

[2966] LCMS: m/z 247 [M+H].sup.+

Example 510

Compound N2-1, Compound N2-2

3-Bromo-8-methoxy-2,3,5,5,6,11-hexahydrospiro[benzo[b]carbazole-6,4-pyran]

1-Bromo-8-methoxy-2,3,5,5,6,11-hexahydrospiro[benzo[b]carbazole-6,4-pyran]

[2967] ##STR00525##

[2968] Under the same conditions as the method for synthesizing Compound A3-1, the title compound was prepared as a mixture from Compound N1.

Example 511

Compound N3

3-Bromo-8-methoxy-2,3,5,6-tetrahydrospiro[benzo[b]carbazole-6,4-pyran]-11(5H)-one

[2969] ##STR00526##

[2970] Under the same conditions as the method for synthesizing Compound A4, the title compound was prepared from Compound N2-1.

[2971] .sup.1H-NMR (300 MHz, DMSO-d.sub.6) : 1.9 (2H, m), 2.4 (m, 2H), 3.9 (s, 3H), 4.0 (m, 2H), 4.2 (m, 2H), 7.1 (dd, 1H, 2.2 Hz, 8.7 Hz), 7.3 (m, 2H), 7.8 (d, 1H, 2.2 Hz), 8.1 (d, 2H, 8.7 Hz), 11.8 (s, 1H)

[2972] LCMS: m/z 413(M+1).sup.+

Example 512

Compound N4

8-Methoxy-11-oxo-2,3,5,5,6,11-hexahydrospiro[benzo[b]carbazole-6,4-pyran]-3-carbonitrile

[2973] ##STR00527##

[2974] Under the same conditions as the method for synthesizing Compound A5-2, the title compound was prepared from Compound N3.

[2975] .sup.1H-NMR (300 MHz, DMSO-d.sub.6) : 1.9 (m, 2H), 2.4 (m, 2H), 3.9 (s, 3H), 4.0 (m, 2H), 4.1 (m, 2H), 7.1 (dd, 1H, 2.2 Hz, 8.7 Hz), 7.4 (d, 1H, 2.2 Hz), 7.6 (dd, 1H, 1.5 Hz, 8.3 Hz), 8.0 (s, 1H), 8.1 (d, 1H, 8.7 Hz), 8.3 (d, 1H, 8.3 Hz), 12.2 (s, 1H)

[2976] LCMS: m/z 359 [M+H].sup.+

[2977] HPLC retention time: 2.80 min (analysis condition U)

Example 513

Compound N5

8-Hydroxy-11-oxo-2,3,5,5,6,11-hexahydrospiro[benzo[b]carbazole-6,4-pyran]-3-carbonitrile

[2978] ##STR00528##

[2979] Under the same conditions as the method for synthesizing Compound A6, the title compound was prepared from Compound N4.

[2980] .sup.1H-NMR (300 MHz, DMSO-d.sub.6) d ppm 2.0 (m, 2H), 2.3 (m, 2H), 4.0 (m, 2H), 4.1 (m, 2H), 6.9 (dd, 1H, 1.9 Hz, 8.3 Hz), 7.3 (d, 1H, 1.9 Hz), 7.6 (dd, 1H, 1.5 Hz, 8.3 Hz), 8.0 (s, 1H), 8.1 (d, 1H, 8.3 Hz), 8.3 (d, 1H, 8.3 Hz), 10.3 (s, 1H), 12.2 (s, 1H)

[2981] LCMS: m/z 345 [M+H].sup.+

[2982] HPLC retention time: 2.37 min (analysis condition U)

Example 514

Compound N6-1-1

(S)-8-((2,2-Dimethyl-1,3-dioxolan-4-yl) methoxy)-11-oxo-2,3,5,5,6,11-hexahydrospiro[benzo[b]carbazole-6,4-pyran]-3-carbonitrile

[2983] ##STR00529##

[2984] Under the same conditions as the method for synthesizing Compound A7-1, the title compound was prepared from Compound N6-2 and (S)-2,2-dimethyl-4-p-tolyloxymethyl-[1,3]dioxolane.

[2985] LCMS: m/z 459 [M+H].sup.+

[2986] HPLC retention time: 2.93 min (analysis condition Y)

Example 515

Compound N6-1-2

(R)-8-(2,3-Dihydroxypropoxy)-1-oxo-2,3,5,5,6,11-hexahydrospiro[benzo[b]carbazole-6,4-pyran]-3-carbonitrile

[2987] ##STR00530##

[2988] Under the same conditions as the method for synthesizing Compound A7-14-2, the title compound was prepared from Compound N6-1-1.

[2989] LCMS: m/z 419 [M+H].sup.+

[2990] HPLC retention time: 1.52 min (analysis condition S)

Example 516

Compound N6-2

11-Oxo-8-(piperidin-4-yloxy)-2,3,5,5,6,11-hexahydrospiro[benzo[b]carbazole-6,4-pyran]-3-carbonitrile

[2991] ##STR00531##

[2992] Under the same conditions as the method for synthesizing Compound A7-1 and Compound A8-1, the title compound was prepared from Compound N5.

[2993] LCMS: m/z 428 [M+H].sup.+

[2994] HPLC retention time: 1.38 min (analysis condition S)

Example 517

Compound N6-3

8-(3-Morpholinoethoxy)-11-oxo-2,3,5,5,6,11-hexahydrospiro[benzo[b]carbazole-6,4-pyran]-3-carbonitrile

[2995] ##STR00532##

[2996] Under the same conditions as the method for synthesizing Compound A8-17, the title compound was prepared from Compound N5.

[2997] LCMS: m/z 458 [M+H].sup.+

[2998] HPLC retention time: 1.33 min (analysis condition S)

Example 518

Compound N6-4

8-(3-Morpholinopropoxy)-11-oxo-2,3,5,5,6,11-hexahydrospiro[benzo[b]carbazole-6,4-pyran]-3-carbonitrile

[2999] ##STR00533##

[3000] Under the same conditions as the method for synthesizing Compound A8-17, the title compound was prepared from Compound N5.

[3001] LCMS: m/z 472 [M+H].sup.+

[3002] HPLC retention time: 1.41 min (analysis condition S)

Example 519

Compound N6-5

3-Cyano-8-[2-(1,1-dioxo-thiomorpholin-4-yl)-ethoxy]-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-9-sulfonic Acid Dimethylamide

[3003] ##STR00534##

[3004] Under the same conditions as the method for synthesizing Compound A8-17, the title compound was prepared from Compound N5.

[3005] LCMS: m/z 506 [M+H].sup.+

[3006] HPLC retention time: 1.53 min (analysis condition S)

Example 520

Compound N6-6

8-(1-Ethylpiperidin-4-yloxy)-11-oxo-2,3,5,5,6,11-hexahydrospiro[benzo[b]carbazole-6,4-pyran]-3-carbonitrile

[3007] ##STR00535##

[3008] Under the same conditions as the method for synthesizing Compound A7-1, the title compound was prepared from Compound N6-2.

[3009] .sup.1H-NMR (300 MHz, DMSO-d.sub.6) : 1.02 (3H, t, 7.25 Hz), 1.18 (2H, m), 1.71 (2H, m), 1.97 (4H, m), 2.27 (2H, m), 2.38 (3H, m), 2.71 (2H, m), 4.03 (2H, m), 4.21 (2H, m), 4.66 (1H, s), 7.13 (1H, dd, 8.77 Hz, 1.91 Hz), 7.39 (1H, bs, 1.91 Hz), 7.60 (1H, d, 8.40 Hz), 8.07 (1H, s), 8.15 (1H, d, 8.40 Hz), 8.37 (1H, d, 8.01 Hz), 12.2 (1 H, s).

[3010] LCMS: m/z 456 [M+H].sup.+

[3011] HPLC retention time: 1.48 min (analysis condition S)

Example 521

Compound N7

Trifluoromethanesulfonic Acid 3-cyano-11-oxo-2,3,5,5,6,11-hexahydrospiro[benzo[b]carbazole-6,4-pyran]-8-yl

[3012] ##STR00536##

[3013] Under the same conditions as the method for synthesizing Compound B1, the title compound was prepared from Compound N5.

[3014] LCMS: m/z 477 [M+H].sup.+

[3015] HPLC retention time: 3.58 min (analysis condition Y)

Example 522

Compound N8-1

11-Oxo-8-(4-(pyrrolidin-1-yl)piperidin-1-yl)-2,3,5,5,6,11-hexahydrospiro[benzo[b]carbazole-6,4-pyran]-3-carbonitrile

[3016] ##STR00537##

[3017] Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound N7 and 4-pyrrolidin-1-yl-piperidine.

[3018] LCMS: m/z 481 [M+H].sup.+

[3019] HPLC retention time: 1.75 min (analysis condition U)

Example 523

Compound N8-2

8-(4-Morpholinopiperidin-1-yl)-11-oxo-2,3,5,5,6,11-hexahydrospiro[benzo[b]carbazole-6,4-pyran]-3-carbonitrile

[3020] ##STR00538##

[3021] Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound N7 and 4-piperidin-4-yl-morpholine.

[3022] LCMS: m/z 497 [M+H].sup.+

[3023] HPLC retention time: 1.70 min (analysis condition U)

Example 524

Compound O1

6-Bromo-7-methoxy-2,3,3,4,5,6-hexahydro-2H-spiro[naphthalene-1,4-pyran]-2-one

[3024] ##STR00539##

[3025] Under the same conditions as the method for synthesizing Compound E-1, the title compound was prepared from Compound N1.

[3026] .sup.1H-NMR (300 MHz, DMSO-d.sub.6) : 2.01 (4H, m), 2.66 (2H, t, 6.87 Hz), 3.08 (2H, t, 6.87 Hz), 3.62 (2H, m), 3.78 (2H, m), 3.87 (3H, s), 7.00 (1H, s), 7.43 (1H, s)

Example 525

Compound O2

9-Bromo-8-methoxy-2,3,5,5,6,11-hexahydrospiro[benzo[b]carbazole-6,4-pyran]-3-carbonitrile

[3027] ##STR00540##

[3028] Under the same conditions as the method for synthesizing Compound E2-1, the title compound was prepared as a crude product from Compound O1.

Example 526

Compound O3

9-Bromo-8-methoxy-11-oxo-2,3,5,5,6,11-hexahydrospiro[benzo[b]carbazole-6,4-pyran]-3-carbonitrile

[3029] ##STR00541##

[3030] Under the same conditions as the method for synthesizing Compound A4, the title compound was prepared from Compound O2.

[3031] .sup.1H-NMR (300 MHz, DMSO-d.sub.6) : 1.95 (2H, d, 14.87 Hz), 2.55 (2H, m), 4.04 (2H, m), 4.09 (3H, s), 4.22 (2H, m), 7.51 (1H, s), 7.63 (1H, dd, 8.01 Hz, 1.53 Hz), 8.09 (1H, s), 8.30 (1H, s), 8.36 (1H, d, 8.01 Hz), 12.3 (1H, s).

[3032] LCMS: m/z 437, 439 [M+H].sup.+

[3033] HPLC retention time: 2.65 min (analysis condition U)

Example 527

Compound O4

9-Fluoro-8-methoxy-11-oxo-2,3,5,5,6,11-hexahydrospiro[benzo[b]carbazole-6,4-pyran]-3-carbonitrile

[3034] ##STR00542##

[3035] Under the same conditions as the method for synthesizing Compound O5-3, the title compound was prepared from Compound O3.

[3036] LCMS: m/z 377 [M+H].sup.+

[3037] HPLC retention time: 2.29 min (analysis condition S)

Example 528

Compound O5-1

9-Fluoro-8-hydroxy-11-oxo-2,3,5,5,6,11-hexahydrospiro[benzo[b]carbazole-6,4-pyran]-3-carbonitrile

[3038] ##STR00543##

[3039] Under the same conditions as the method for synthesizing Compound E3-2, the title compound was prepared from Compound O4.

[3040] LCMS: m/z 363 [M+H].sup.+

[3041] HPLC retention time: 1.88 min (analysis condition S)

Example 529

Compound O5-2

Trifluoromethanesulfonic Acid 3-cyano-9-fluoro-11-oxo-2,3,5,5,6,11-hexahydrospiro[benzo[b]carbazole-6,4-pyran]-8-yl

[3042] ##STR00544##

[3043] Under the same conditions as the method for synthesizing Compound B1, the title compound was prepared from Compound O5-1.

[3044] LCMS: m/z 495 [M+H].sup.+

[3045] HPLC retention time: 3.47 min (analysis condition Y)

Example 530

Compound O5-3

9-Fluoro-11-oxo-8-(4-(pyrrolidin-1-yl)piperidin-1-yl)-2,3,5,5,6,11-hexahydrospiro[benzo[b]carbazole-6,4-pyran]-3-carbonitrile

[3046] ##STR00545##

[3047] To the THF (0.9 ml) solution of 9-bromo-6-tetrahydropyran-8-pyrrolidinopiperidin-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (Compound O8-1, 90 mg, 0.161 mmol), THF solution of n-butyl lithium (2 M solution, 0.241 ml, 3 eq.) was added at 78 C. After stirring for 30 min, THF (1 ml) solution of N fluorobenzenesulfonimide (152 mg, 3 eq.) was added dropwise thereto. After rising to room temperature, the mixture was stirred for 18 hr. To the reaction solution, water was added and the extraction was carried out with ethyl acetate. The organic layer was washed with brine and dried over magnesium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were purified by high performance chromatography to obtain the target compound (white solid, 0.44 mg, 0.5%).

[3048] .sup.1H-NMR (CDCl.sub.3+CD.sub.3OD, 300 MHz): 1.75-1.94 (m, 11H), 2.02-2.01 (m, 2H), 2.30-2.27 (m, 1H), 2.75-2.72 (m, 2H), 2.90-3.00 (m, 2H), 3.61-3.47 (m, 4H), 4.01-3.90 (m, 4H), 7.08 (dd, 1H, J=1, 2 Hz, 8.4 Hz), 7.29 (dd, 1H, J=1, 5 Hz, 8.1 Hz), 7.68 (d, 1H, J=12.9 Hz), 7.72 (s, 1H), 8.22 (d, 1H, J=8.4 Hz)

[3049] LCMS: m/z 499 [M+H].sup.+

[3050] HPLC retention time: 1.95 min (analysis condition U)

Example 531

Compound O5-4

8-(4-Cyclobutylpiperazin-1-yl)-9-fluoro-11-oxo-2,3,5,5,6,11-hexahydrospiro[benzo[b]carbazole-6,4-pyran]-3-carbonitrile

[3051] ##STR00546##

[3052] Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound O5-2 and 1-cyclobutylpiperazine.

[3053] LCMS: m/z 485 [M+H].sup.+

[3054] HPLC retention time: 1.97 min (analysis condition U)

Example 532

Compound O6-1

9-Bromo-8-hydroxy-11-oxo-2,3,5,5,6,11-hexahydrospiro[benzo[b]carbazole-6,4-pyran]-3-carbonitrile

[3055] ##STR00547##

[3056] Under the same conditions as the method for synthesizing Compound A6, the title compound was prepared from Compound O3.

[3057] LCMS: m/z 423, 425 [M+H].sup.+

[3058] HPLC retention time: 2.30 min (analysis condition U)

Example 533

Compound O6-2

Trifluoromethanesulfonic Acid 9-bromo-3-cyano-11-oxo-2,3,5,5,6,11-hexahydrospiro[benzo[b]carbazole-6,4-pyran]-8-yl

[3059] ##STR00548##

[3060] Under the same conditions as the method for synthesizing Compound B1, the title compound was prepared from Compound O6-1.

[3061] LCMS: m/z 555, 557 [M+H].sup.+

[3062] HPLC retention time: 3.13 min (analysis condition U)

Example 534

Compound O7-1

9-Bromo-11-oxo-8-(piperazin-1-yl)-2,3,5,5,6,11-hexahydrospiro[benzo[b]carbazole-6,4-pyran]-3-carbonitrile

[3063] ##STR00549##

[3064] Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound O6-2 and piperazine.

[3065] LCMS: m/z 491, 493 [M+H].sup.+

[3066] HPLC retention time: 1.88 min (analysis condition U)

Example 535

Compound O7-2

4-(9-Bromo-3-cyano-11-oxo-2,3,5,5,6,11-hexahydrospiro[benzo[b]carbazole-6,4-pyran]-8-yl)piperazine-1-carboxylic Acid Tert-Butyl

[3067] ##STR00550##

[3068] To the dichloromethane (5 mL) solution of 9-bromo-11-oxo-8-(piperazin-1-yl)-2,3,5,5,6,11-hexahydrospiro[benzo[b]carbazole-6,4-pyran]-3-carbonitrile (Compound 07-1, 250 mg, 0.509 mmol) and mono-tert-butyl ester carbonic anhydride (122 mg, 0.560 mmol), triethylamine (0.21 mL, 1.53 mmol) was added at 0 C., and stirred at room temperature for 1 hr. The reaction mixture was concentrated under reduced pressure and the residues were purified by silica gel column chromatography (methanol/dichloromethane) to obtain the target compound as a white solid (212 mg, 70%).

[3069] .sup.1H-NMR (300 MHz, DMSO-d.sub.6) d ppm: 1.44 (9H, s), 1.97 (2H, m), 2.44 (2H, m), 1.35 (4H, m), 3.54 (4H, m), 4.06 (2H, m), 4.18 (2H, m), 7.57 (1H, s), 7.63 (1H, dd, 8.01 Hz, 1.52 Hz), 8.08 (1H, d, 1.52 Hz), 8.31 (1H, s), 8.36 (1H, d, 8.01 Hz), 12.3 (1H, s)

[3070] LCMS: m/z 591, 593 [M+H].sup.+

[3071] HPLC retention time: 3.23 min (analysis condition T)

Example 536

Compound O7-3

Tert-butyl 4-(3-cyano-11-oxo-9-(prop-1-ynyl)-2,3,5,5,6,11-hexahydrospiro[benzo[b]carbazole-6,4-pyran]-8-yl)piperazine-1-carboxylic Acid

[3072] ##STR00551##

[3073] Under the same conditions as the method for synthesizing Compound O9-1, the title compound was prepared from Compound O7-2.

[3074] LCMS: m/z 551 [M+H].sup.+

[3075] HPLC retention time: 3.92 min (analysis condition Y)

Example 537

Compound O7-4

11-Oxo-8-(piperazin-1-yl)-9-(prop-1-ynyl)-2,3,5,5,6,11-hexahydrospiro[benzo[b]carbazole-6,4-pyran]-3-carbonitrile

[3076] ##STR00552##

[3077] Under the same conditions as the method for synthesizing Compound A8-1, the title compound was prepared from Compound O7-3.

[3078] LCMS: 451 m/z [M+H].sup.+

[3079] HPLC retention time: 1.87 min (analysis condition U)

Example 538

Compound O7-5

4-(3-Cyano-9-ethynyl-11-oxo-2,3,5,5,6,11-hexahydrospiro[benzo[b]carbazole-6,4-pyran]-8-yl)piperazine-1-carboxylic acid tert-butyl

[3080] ##STR00553##

[3081] LCMS: m/z 537 [M+H].sup.+

[3082] HPLC retention time: 3.82 min (analysis condition Y)

Example 539

Compound O8-1

9-Bromo-11-oxo-8-(4-(pyrrolidin-1-yl)piperidin-1-yl)-2,3,5,5,6,11-hexahydrospiro[benzo[b]carbazole-6,4-pyran]-3-carbonitrile

[3083] ##STR00554##

[3084] Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound O6-2 and 4-pyrrolidin-1-yl-piperidine.

[3085] LCMS: m/z 559, 561 [M+H].sup.+

[3086] HPLC retention time: 2.05 min (analysis condition U)

Example 540

Compound O8-2

9-Bromo-8-(4-cyclobutylpiperazin-1-yl)-11-oxo-2,3,5,5,6,11-hexahydrospiro[benzo[b]carbazole-6,4-pyran]-3-carbonitrile

[3087] ##STR00555##

[3088] Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound O6-2 and 1-cyclobutylpiperazine.

[3089] LCMS: m/z 547 [M+H].sup.+

[3090] HPLC retention time: 1.61 min (analysis condition S)

Example 541

Compound O8-3

9-Bromo-8-(4-morpholinopiperidin-1-yl)-11-oxo-2,3,5,5,6,11-hexahydrospiro[benzo[b]carbazole-6,4-pyran]-3-carbonitrile

[3091] ##STR00556##

[3092] Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound O6-2 and 4-piperidin-4-yl-morpholine.

[3093] LCMS: m/z 575, 577 [M+H].sup.+

[3094] HPLC retention time: 1.95 min (analysis condition U)

Example 542

Compound O8-4

9-Bromo-8-(4-(oxetan-3-yl)piperazin-1-yl)-11-oxo-2,3,5,5,6,11-hexahydrospiro[benzo[b]carbazole-6,4-pyran]-3-carbonitrile

[3095] ##STR00557##

[3096] Under the same conditions as the method for synthesizing Compound B3-32, the title compound was prepared from Compound O7-1 and oxetan-3-one.

[3097] LCMS: m/z 547, 549 [M+H].sup.+

[3098] HPLC retention time: 1.43 min (analysis condition S)

Example 543

Compound O8-5

9-Bromo-8-(4-tert-butylpiperazin-1-yl)-11-oxo-2,3,5,5,6,11-hexahydrospiro[benzo[b]carbazole-6,4-pyran]-3-carbonitrile

[3099] ##STR00558##

[3100] Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound O6-2 and 1-tert-butylpiperazine.

[3101] LCMS: 547, 549 m/z [M+H].sup.+

[3102] HPLC retention time: 2.07 min (analysis condition U)

Example 544

Compound O9-1

11-Oxo-9-(prop-1-ynyl)-8-(4-(pyrrolidin-1-yl)piperidin-1-yl)-2,3,5,5,6,11-hexahydrospiro[benzo[b]carbazole-6,4-pyran]-3-carbonitrile

[3103] ##STR00559##

[3104] 9-Bromo-11-oxo-8-(4-(pyrrolidin-1-yl)piperidin-1-yl)-2,3,5,5,6,11-hexahydrospiro[benzo[b]carbazole-6,4-pyran]-3-carbonitrile (Compound O8-1, 100 mg, 0.170 mmol), tin tributyl(1-propynyl) (0.082 mL, 0.268 mmol), bis(acetonitrile) palladium dichloride (II) (2.64 mg, 0.00895 mmol), X-Phos (12.8 mg, 0.0269 mmol), and cesium carbonate (262.4 mg, 0.806 mmol) were suspended in acetonitrile (1 mL), and then stirred at 80 C. for 2 hr. The reaction mixture was cooled to room temperature followed by addition of water and extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (dichloromethane/methanol) to obtain the target compound (pale yellow solid, 3.8 mg, 4.1%).

[3105] .sup.1H-NMR (300 MHz, DMSO) ppm 12.20 (bs, 1H), 8.35 (d, 1H, J=8.1 Hz), 8.06 (s, 1H), 8.06 (d, 1H, J=10.8 Hz), 7.58 (d, 1H, J=8.4 Hz), 7.29 (s, 1H), 4.25-4.23 (m, 2H), 4.02-3.98 (m, 2H), 3.78 (d, 2H, J=11.4 Hz), 2.93 (t, 2H, J=11.1 Hz), 2.55 (s, 1H), 2.45-2.28 (m, 2H), 2.24-2.05 (m, 4H), 2.08-1.81 (m, 4H), 1.75-1.50 (m, 7H)

[3106] LCMS: m/z 519 [M+H].sup.+

[3107] HPLC retention time: 1.98 min (analysis condition U)

Example 545

Compound O9-2

9-Ethynyl-11-oxo-8-(4-(pyrrolidin-1-yl)piperidin-1-yl)-2,3,5,5,6,11-hexahydrospiro[benzo[b]carbazole-6,4-pyran]-3-carbonitrile

[3108] ##STR00560##

[3109] Under the same conditions as the method for synthesizing Compound F5-43, the title compound was prepared from Compound O8-1.

[3110] LCMS: m/z 505 [M+H].sup.+

[3111] HPLC retention time: 1.92 min (analysis condition U)

Example 546

Compound O9-3

11-Oxo-8-(4-(pyrrolidin-1-yl)piperidin-1-yl)-2,3,5,5,6,11-hexahydrospiro[benzo[b]carbazole-6,4-pyran]-3,9-dicarbonitrile

[3112] ##STR00561##

[3113] Under the same conditions as the method for synthesizing Compound A5-2, the title compound was prepared from Compound O8-1.

[3114] LCMS: 506 m/z [M+H].sup.+

[3115] HPLC retention time: 1.87 min (analysis condition U)

Example 547

Compound O9-4

9-(3-Hydroxy-3-methylbut-1-ynyl)-11-oxo-8-(4-(pyrrolidin-1-yl)piperidin-1-yl)-2,3,5,5,6,11-hexahydrospiro[benzo[b]carbazole-6,4-pyran]-3-carbonitrile

[3116] ##STR00562##

[3117] Under the same conditions as the method for synthesizing Compound E4-2-1, the title compound was prepared from Compound O8-1.

[3118] LCMS: m/z 563 [M+H].sup.+

[3119] HPLC retention time: 1.92 min (analysis condition U)

Example 548

Compound O9-5

8-(4-Cyclobutylpiperazin-1-yl)-11-oxo-9-(prop-1-ynyl)-2,3,5,5,6,11-hexahydrospiro[benzo[b]carbazole-6,4-pyran]-3-carbonitrile

[3120] ##STR00563##

[3121] Under the same conditions as the method for synthesizing Compound O9-1, the title compound was prepared from Compound O8-2.

[3122] .sup.1H-NMR (300 MHz, DMSO-d.sub.6) : 1.6 (m, 2H), 1.8 (m, 2H), 1.9 (m, 4H), 2.1 (s, 3H), 2.4 (m, 6H), 2.8 (m, 1H), 3.4 (m, 4H), 4.0 (m, 2H), 4.1 (m, 2H), 7.3 (s, 1H), 7.6 (d, 1H, 8.0 Hz), 8.0 (m, 2H), 8.3 (d, 1H, 8.0 Hz), 12.2 (s, 1H)

[3123] LCMS: m/z 505 [M+H].sup.+

[3124] HPLC retention time: 2.03 min (analysis condition U)

Example 549

Compound O9-6

8-(4-Cyclobutylpiperazin-1-yl)-9-ethynyl-11-oxo-2,3,5,5,6,11-hexahydrospiro[benzo[b]carbazole-6,4-pyran]-3-carbonitrile

[3125] ##STR00564##

[3126] Under the same conditions as the method for synthesizing Compound F5-43, the title compound was prepared from Compound O8-2.

[3127] .sup.1H-NMR (300 MHz, DMSO-d.sub.6) : 1.66 (2H, m), 1.83 (2H, t, 8.77 Hz), 1.99 (4H, m), 2.41 (6H, m), 2.79 (1H, t, 7.63 Hz), 3.35 (4H, m), 4.01 (2H, m), 4.27 (2H, m), 4.51 (1H, s), 7.33 (1H, s), 7.54 (1H, m), 8.03 (1H, s), 8.16 (1H, s), 8.32 (1H, d, 8.40 Hz), 12.3 (1H, s).

[3128] LCMS: m/z 491 [M+H].sup.+

[3129] HPLC retention time: 1.95 min (analysis condition U)

Example 550

Compound O9-7

8-(4-Morpholinopiperidin-1-yl)-1-oxo-9-(prop-1-ynyl)-2,3,5,5,6,11-hexahydrospiro[benzo[b]carbazole-6,4-pyran]-3-carbonitrile

[3130] ##STR00565##

[3131] Under the same conditions as the method for synthesizing Compound O9-1, the title compound was prepared from Compound O8-3.

[3132] .sup.1H-NMR (300 MHz, DMSO-d.sub.6) : 1.57 (2H, m), 1.95 (4H, m), 2.14 (3H, s), 2.37 (3H, m), 3.35 (4H, m), 2.83 (2H, t, 12.6 Hz), 3.56 (4H, s), 3.86 (2H, d, 11.8 Hz), 4.04 (2H, m), 4.17 (2H, m), 7.31 (1H, s), 7.61 (1H, d, 8.01 Hz), 8.06 (1H, s), 8.07 (1H, s), 8.36 (1H, d, 8.01 Hz), 12.3 (1H, s).

[3133] LCMS: m/z 535 [M+H].sup.+

[3134] HPLC retention time: 1.95 min (analysis condition U)

Example 551

Compound O9-8

9-Ethynyl-8-(4-morpholinopiperidin-1-yl)-11-oxo-2,3,5,5,6,11-hexahydrospiro[benzo[b]carbazole-6,4-pyran]-3-carbonitrile

[3135] ##STR00566##

[3136] Under the same conditions as the method for synthesizing Compound F5-43, the title compound was prepared from compound 08-3.

[3137] LCMS: m/z 521 [M+H].sup.+

[3138] HPLC retention time: 1.90 min (analysis condition U)

Example 552

Compound O9-9

8-(4-(Oxetan-3-yl)piperazin-1-yl)-11-oxo-9-(prop-1-ynyl)-2,3,5,5,6,11-hexahydrospiro[benzo[b]carbazole-6,4-pyran]-3-carbonitrile

[3139] ##STR00567##

[3140] Under the same conditions as the method for synthesizing Compound B3-32, the title compound was prepared from Compound O7-4 and oxetan-3-one.

[3141] LCMS: m/z 507 [M+H].sup.+

[3142] HPLC retention time: 1.43 min (analysis condition S)

Example 553

Compound O10-1-1

[3143] Tert-butyl4-(3-cyano-9-ethyl-11-oxo-2,3,5,5a, 5,6,11,11a-octahydrospiro[benzo[b]carbazole-6,4-pyran]-8-yl)piperazine-1-carboxylic acid

##STR00568##

[3144] Under the same conditions as the method for synthesizing Compound B3-13-1, the title compound was prepared from Compound O7-5.

[3145] LCMS: m/z 541 [M+H].sup.+

[3146] HPLC retention time: 3.08 min (analysis condition S)

Example 554

Compound O10-1-2

9-Ethyl-11-oxo-8-(piperazin-1-yl)-2,3,5,5,6,11-hexahydrospiro[benzo[b]carbazole-6,4-pyran]-3-carbonitrile

[3147] ##STR00569##

[3148] Under the same conditions as the method for synthesizing Compound A8-1, the title compound was prepared from Compound O10-1-1.

[3149] LCMS: m/z 441 [M+H].sup.+

[3150] HPLC retention time: 1.42 min (analysis condition S)

Example 555

Compound O10-2

9-Ethyl-8-(4-morpholinopiperidin-1-yl)-11-oxo-2,3,5,5,6,11-hexahydrospiro[benzo[b]carbazole-6,4-pyran]-3-carbonitrile

[3151] ##STR00570##

[3152] According to the same method as the method for synthesizing Compound B3-13-1, the title compound was prepared from Compound O9-8.

[3153] .sup.1H-NMR (400 MHz, DMSO-d.sub.6) : 8.23-8.21 (1H, m), 8.02-8.00 (1H, m), 7.88-7.86 (1H, m), 7.39-7.36 (2H, m), 4.63-4.59 (2H, m), 3.89-3.85 (2H, m), 3.60-3.56 (6H, m), 3.22-3.19 (4H, m), 2.76-2.68 (4H, m), 2.37-2.32 (3H, m), 1.92-1.88 (2H, m), 1.75-1.72 (2H, m), 1.61-1.57 (2H, m), 1.27-1.25 (3H, m)

[3154] LCMS: m/z 525 [M+H].sup.+

[3155] HPLC retention time: 1.48 min (analysis condition S)

Example 556

Compound O10-3

9-Ethyl-8-(4-(oxetan-3-yl)piperazin-1-yl)-11-oxo-2,3,5,5,6,11-hexahydrospiro[benzo[b]carbazole-6,4-pyran]-3-carbonitrile

[3156] ##STR00571##

[3157] Under the same conditions as the method for synthesizing Compound B3-32, the title compound was prepared from Compound O10-1-2 and oxetan-3-one.

[3158] .sup.1H-NMR (400 MHz, DMSO-d.sub.6) : 12.26 (1H, s), 8.39 (1H, d, 7.9 Hz), 8.09-8.07 (2H, m), 7.63 (1H, d, 8.5 Hz), 7.51 (1H, s), 4.60-4.50 (4H, m), 4.20-4.09 (4H, m), 3.56-3.51 (1H, m), 3.07-3.05 (4H, m), 2.76-2.70 (2H, m), 2.44-2.40 (2H, m), 2.02-1.98 (2H, m), 1.29-1.26 (4H, m)

[3159] LCMS: m/z 497 [M+H].sup.+

[3160] HPLC retention time: 1.42 min (analysis condition S)

Example 557

Compound O10-4

8-(4-Cyclobutylpiperazin-1-yl)-9-ethyl-11-oxo-2,3,5,5,6,11-hexahydrospiro[benzo[b]carbazole-6,4-pyran]-3-carbonitrile

[3161] ##STR00572##

[3162] Under the same conditions as the method for synthesizing Compound B3-32, the title compound was prepared from Compound O10-1-2 and cyclobutanone.

[3163] LCMS: m/z 495 [M+H].sup.+

[3164] HPLC retention time: 1.57 min (analysis condition S)

Example 558

Compound P1 (Intermediate)

8-Methoxy-6,6-dimethyl-2-nitro-6,11-dihydro-5H-benzo[b]carbazole

[3165] ##STR00573##

[3166] Under the same conditions as the method for synthesizing Compound A3-1, the title compound was prepared from Compound A2 and 4-nitrophenylhydrazine.

[3167] LCMS: m/z 323 [M+H].sup.+

[3168] HPLC retention time: 4.08 min (analysis condition W)

Example 559

Compound P2 (Intermediate)

8-Methoxy-6,6-dimethyl-2-nitro-5,6-dihydro-benzo[b]carbazol-11-one

[3169] ##STR00574##

[3170] Under the same conditions as the method for synthesizing Compound A4, the title compound was prepared from Compound P1.

[3171] .sup.1H-NMR (400 MHz, DMSO-d.sub.6) : 12.85 (1H, s), 9.03 (1H, d, J=1.9 Hz), 8.17-8.20 (2H, m), 7.71 (1H, d, J=9.1 Hz), 7.38 (1H, d, J=2.4 Hz), 7.12 (1H, dd, J=8.5, 2.4 Hz), 3.93 (3H, s), 1.79 (6H, s)

[3172] LCMS: m/z 337 [M+H].sup.+

[3173] HPLC retention time: 3.55 min (analysis condition W)

Example 560

Compound P3 (Intermediate)

8-Hydroxy-6,6-dimethyl-2-nitro-5,6-dihydro-benzo[b]carbazol-11-one

[3174] ##STR00575##

[3175] Under the same conditions as the method for synthesizing Compound A6, the title compound was prepared from Compound P2.

[3176] LCMS: m/z 323 [M+H].sup.+

[3177] HPLC retention time: 3.11 min (analysis condition W)

Example 561

Compound P4 (Intermediate)

4-(6,6-Dimethyl-2-nitro-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-8-yl oxy)-piperidine-1-Carboxylic Acid Tert-Butyl Ester

[3178] ##STR00576##

[3179] Under the same conditions as the method for synthesizing Compound A7-1, the title compound was prepared from Compound P3.

[3180] .sup.1H-NMR (400 MHz, CDCl.sub.3) : 9.40 (1H, s), 9.37 (1H, s), 8.41 (1H, d, J=8.5 Hz), 8.24 (1H, d, J=11.0 Hz), 7.51 (1H, d, J=8.5 Hz), 7.13 (1H, s), 7.03 (1H, d, J=9.1 Hz), 4.61-4.71 (1H, m), 3.69-3.84 (2H, m), 3.35-3.49 (2H, m), 1.94-2.10 (2H, m), 1.75-1.93 (8H, m), 1.50 (9H, s)

[3181] LCMS: m/z 506 [M+H].sup.+

[3182] HPLC retention time: 4.17 min (analysis condition W)

Example 562

Compound P5

2-Amino-6,6-dimethyl-8-(piperidin-4-yloxy)-5,6-dihydro-benzo[b]carbazol-11-one

[3183] ##STR00577##

[3184] Under the same conditions as the method for synthesizing Compound A8-1, the title compound was prepared from Compound P6.

[3185] .sup.1H-NMR (400 MHz, CD.sub.3OD) : 8.23 (1H, d, J=8.5 Hz), 7.68 (1H, d, J=2.4 Hz), 7.26 (1H, d, J=8.5 Hz), 7.24 (1H, d, J=2.4 Hz), 7.06 (1H, dd, J=8.5, 2.4 Hz), 6.80 (1H, dd, J=8.5, 2.4 Hz), 4.64-4.71 (1H, m), 3.06-3.15 (2H, m), 2.73-2.83 (2H, m), 2.02-2.13 (2H, m), 1.67-1.82 (8H, m)

[3186] LCMS: m/z 506 [M+H].sup.+

[3187] HPLC retention time: 4.17 min (analysis condition W)

Example 563

Compound P6 (Intermediate)

4-(2-Amino-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-8-yl oxy)-piperidine-1-carboxylic Acid Tert-Butyl Ester

[3188] ##STR00578##

[3189] To the ethanol (8 ml) suspension of 4-(6,6-dimethyl-2-nitro-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-8-yl oxy)-piperidine-1-carboxylic acid tert-butyl ester (Compound P4, 103 mg, 0.204 mmol), iron powder (228 mg, 20 eq.), ammonium chloride (109 mg, 10 eq.), and distilled water (4 ml) were added and the mixture was stirred at 90 C. for 30 min. Upon the completion of the reaction, insoluble matters were filtered off, and the filtrate was extracted with ethyl acetate. The organic layer was washed with brine and dried over sodium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain the title compound (115 mg, 57%).

[3190] LCMS: m/z 476 [M+H].sup.+

[3191] HPLC retention time: 2.82 min (analysis condition W)

Example 564

Compound P7 (Intermediate)

4-(2-Methanesulfonylamino-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-8-yl oxy)-piperidine-1-carboxylic Acid Tert-Butyl Ester

[3192] ##STR00579##

[3193] To the pyridine (2 ml) solution of 4-(2-amino-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-8-yl oxy)-piperidine-1-carboxylic acid tert-butyl ester (Compound P6, 50 mg, 0.105 mmol), mesyl chloride (9 l, 1.2 eq.) was added and stirred at room temperature for 30 min. Upon the completion of the reaction, the reaction solution was concentrated under reduced pressure to obtain the title compound as an unpurified product.

[3194] LCMS: m/z 554 [M+H].sup.+

[3195] HPLC retention time: 3.60 min (analysis condition W)

Example 565

Compound P8

N-[6,6-Dimethyl-11-oxo-8-(piperidin-4-yloxy)-6,11-dihydro-5H-benzo[b]carbazole-2-yl]-methanesulfonamide

[3196] ##STR00580##

[3197] Under the same conditions as the method for synthesizing Compound A8-1, the title compound was prepared from Compound P7.

[3198] .sup.1H-NMR (400 MHz, CD.sub.3OD) : 8.25 (1H, d, J=8.5 Hz), 8.16 (1H, d, J=1.8 Hz), 7.46 (1H, d, J=9.1 Hz), 7.27-7.29 (2H, m), 7.09 (1H, dd, J=9.1, 1.8 Hz), 4.67-4.75 (1H, m), 3.09-3.18 (2H, m), 2.95 (3H, s), 2.77-2.87 (2H, m), 1.70-1.84 (8H, m)

[3199] LCMS: m/z 454 [M+H].sup.+

[3200] HPLC retention time: 2.22 min (analysis condition W)

Example 566

Compound Q3 (Intermediate)

2-Fluoro-8-methoxy-6,6-dimethyl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[3201] ##STR00581##

[3202] Under the same conditions as the method for synthesizing Compound A3-1, the title compound was prepared from Compound A2 and 3-cyano-4-fluorophenylhydrazine.

[3203] LCMS: m/z 321 [M+H].sup.+

[3204] HPLC retention time: 4.13 min (analysis condition W)

Example 567

Compound Q4 (Intermediate)

2-Fluoro-8-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[3205] ##STR00582##

[3206] Under the same conditions as the method for synthesizing Compound A4, the title compound was prepared from Compound Q3.

[3207] .sup.1H-NMR (400 MHz, DMSO-d.sub.6) : 12.89 (1H, s), 8.16 (1H, d, J=8.5 Hz), 8.07 (1H, d, J=4.9 Hz), 8.04 (1H, d, J=9.8 Hz), 7.36 (1H, d, J=2.4 Hz), 7.10 (1H, dd, J=8.5, 2.4 Hz), 3.91 (3H, s), 1.78 (3H, s)

[3208] LCMS: m/z 335 [M+H].sup.+

[3209] HPLC retention time: 3.61 min (analysis condition W)

Example 568

Compound Q5 (Intermediate)

2-Fluoro-8-hydroxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[3210] ##STR00583##

[3211] Under the same conditions as the method for synthesizing Compound A6, the title compound was prepared from Compound Q4.

[3212] LCMS: m/z 321 [M+H].sup.+

[3213] HPLC retention time: 3.16 min (analysis condition W)

Example 569

Compound Q6 (Intermediate)

4-(3-Cyano-2-fluoro-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-8-yl oxy)-piperidine-1-carboxylic Acid Tert-Butyl Ester

[3214] ##STR00584##

[3215] Under the same conditions as the method for synthesizing Compound A7-1, the title compound was prepared from Compound Q5.

[3216] LCMS: m/z 504 [M+H].sup.+

[3217] HPLC retention time: 4.25 min (analysis condition W)

Example 570

Compound Q7

8-(2-Diethylamino-ethoxy)-2-fluoro-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[3218] ##STR00585##

[3219] Under the same conditions as the method for synthesizing Compound A7-17, the title compound was prepared from Compound Q5.

[3220] .sup.1H-NMR (400 MHz, CD.sub.3OD) : 8.25 (1H, d, J=8.5 Hz), 8.09 (1H, d, J=9.8 Hz), 7.83 (1H, d, J=5.5 Hz), 7.30 (1H, d, J=2.4 Hz), 7.09 (1H, dd, J=8.5, 2.4 Hz), 4.26 (2H, t, J=5.7 Hz), 2.98 (2H, t, J=5.7 Hz), 2.72 (4H, q, J=7.2 Hz), 1.81 (6H, s), 1.13 (6H, t, J=7.2 Hz)

[3221] LCMS: m/z 420 [M+H].sup.+

[3222] HPLC retention time: 2.65 min (analysis condition W)

Example 571

Compound Q8

2-Fluoro-6,6-dimethyl-11-oxo-8-(piperidin-4-yloxy)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[3223] ##STR00586##

[3224] Under the same conditions as the method for synthesizing Compound A8-1, the title compound was prepared from Compound Q6.

[3225] .sup.1H-NMR (400 MHz, DMSO-d.sub.6) : 8.11 (1H, d, J=8.5 Hz), 7.98 (1H, d, J=5.5 Hz), 7.96 (1H, d, J=9.8 Hz), 7.29 (1H, s), 7.08 (1H, d, J=8.5 Hz), 4.58-4.69 (1H, m), 2.93-3.05 (2H, m), 2.60-2.69 (2H, m), 1.94-2.03 (2H, m), 1.74 (6H, s), 1.45-1.57 (2H, m)

[3226] LCMS: m/z 404 [M+H].sup.+

[3227] HPLC retention time: 2.67 min (analysis condition W)

Example 572

Compound R2

2-Fluoro-3-hydrazinylbenzonitrile

[3228] ##STR00587##

[3229] 3-Amino-2-fluoro-benzonitrile (100 mg, 0.735 mmol) was dissolved in water (0.94 mL), added with conc. hydrochloric acid (0.74 mL) at 0 C., and then further added with an aqueous solution (0.294 mL) of sodium nitrite (61 mg, 0.882 mmol). The resulting mixture was stirred at 0 C. for 1 hr. To the reaction mixture, conc. hydrochloric acid solution (0.94 mL) of tin chloride (321 mg, 1.69 mmol) was added and stirred at room temperature for 1 hr. Thereafter, the reaction solution was neutralized with aqueous solution of sodium hydroxide, and extracted with dichloromethane. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The drying agent was removed by filtration and the residues were obtained after concentration under reduced pressure to give the target compound as a crude product.

Example 573

Compound R3

4-Fluoro-8-methoxy-6,6-dimethyl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[3230] ##STR00588##

[3231] Under the same conditions as the method for synthesizing Compound E2-1, the title compound was prepared as a crude product from Compound A2 and Compound R2.

Example 574

Compound R4

4-Fluoro-8-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[3232] ##STR00589##

[3233] Under the same conditions as the method for synthesizing Compound A4, the title compound was prepared from Compound R3.

[3234] LCMS: m/z 335 [M+H].sup.+

[3235] HPLC retention time: 2.70 min (analysis condition U)

Example 575

Compound R5

4-Fluoro-8-hydroxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[3236] ##STR00590##

[3237] Under the same conditions as the method for synthesizing Compound A6, the title compound was prepared from Compound R4.

[3238] LCMS: m/z 321 [M+H].sup.+

[3239] HPLC retention time: 2.32 min (analysis condition U)

Example 576

Compound R6

8-(2-Diethylamino-ethoxy)-4-fluoro-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[3240] ##STR00591##

[3241] Under the same conditions as the method for synthesizing Compound A7-17, the title compound was prepared from Compound R5.

[3242] LCMS: m/z 420 [M+H].sup.+

[3243] HPLC retention time: 1.51 min (analysis condition S)

Example 577

Compound R7

Trifluoromethanesulfonic Acid 3-cyano-4-fluoro-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-8-yl

[3244] ##STR00592##

[3245] Under the same conditions as the method for synthesizing Compound B1, the title compound was prepared from Compound R5.

[3246] LCMS: m/z 453 [M+H].sup.+

[3247] HPLC retention time: 3.82 min (analysis condition Y)

Example 578

Compound R8-1

4-Fluoro-6,6-dimethyl-11-oxo-8-(4-pyrrolidin-1-yl-piperidin-1-yl)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[3248] ##STR00593##

[3249] Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound R7 and 4-pyrrolidin-1-yl-piperidine.

[3250] LCMS: m/z 457 [M+H].sup.+

[3251] HPLC retention time: 2.10 min (analysis condition U)

Example 579

Compound R8-2

4-Fluoro-8-(4-isopropyl-piperazin-1-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[3252] ##STR00594##

[3253] Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound R7.

[3254] LCMS: m/z 431 [M+H].sup.+

[3255] HPLC retention time: 2.07 min (analysis condition U)

Example 580

Compound R9-1

8-((S)-2,2-Dimethyl-[1,3]dioxolan-4-yl methoxy)-4-fluoro-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[3256] ##STR00595##

[3257] Under the same conditions as the method for synthesizing Compound A7-1, the title compound was prepared as a crude product from Compound R5 and (R)-()-2,2-dimethyl-1,3-dioxolan-4-methanol.

Example 581

Compound R9-2

8-((R)-2,3-Dihydroxy-propoxy)-4-fluoro-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[3258] ##STR00596##

[3259] Under the same conditions as the method for synthesizing Compound A7-14-2, the title compound was prepared from Compound R9-1 (9.9 mg, 80%).

[3260] LCMS: m/z 395 [M+H].sup.+

[3261] HPLC retention time: 2.38 min (analysis condition C)

Example 582

Compound S1-1

3-Chloro-8-methoxy-6,6-dimethyl-5,6-dihydrobenzo[b]carbazol-11-one

[3262] ##STR00597##

[3263] Under the same conditions as the method for synthesizing Compound A3-1 and Compound A4, the title compound was prepared as a crude product from Compound A2 and (3-chlorophenyl)-hydrazine hydrochloric acid salt

Example 583

Compound S1-2

3-Chloro-8-methoxy-2,6,6-trimethyl-5,6-dihydro-benzo[b]carbazol-11-one

[3264] ##STR00598##

[3265] 7-Methoxy-1,1-dimethyl-3,4-dihydro-1H-naphthalen-2-one (Compound A2, 99.1 mg, 0.485 mmol) and (3-chloro-4-methyl-phenyl)hydrazine hydrochloric acid salt (100.4 mg, 1.1 eq.) were dissolved in TFA (1 mL) and the mixture was irradiated with microwave at 80 C. for 10 min under nitrogen atmosphere. After cooling, the reaction solution was added with ethyl acetate, washed with water, saturated aqueous solution of sodium hydrogen carbonate and saturated brine and dried over magnesium sulfate. After filtration and concentration under reduced pressure, the residues obtained therefrom were dissolved in THF (2 mL) and water (0.2 mL), added with DDQ (125.7 mg, 1.1 eq.), and stirred at room temperature overnight. The reaction solution was added with the mixture solvent of hexane and ethyl acetate, and the starting-point components were removed by dry type silica gel column. The eluent was concentrated under reduced pressure, and the resulting residues were purified by preparative TLC (methanol/dichloromethane) to obtain the title compound (19.4 mg, 12%).

[3266] .sup.1H-NMR (400 MHz, DMSO-d.sub.6) : 12.2 (1H, s), 8.15 (1H, d, J=8.8 Hz), 8.12 (1H, s), 7.52 (1H, s), 7.32 (1H, s), 7.07 (1H, dd, J=2.4, 8.8 Hz), 3.90 (3H, s), 2.45 (3H, s), 1.73 (6H, s),

[3267] LCMS: m/z 340 [M+H].sup.+

[3268] HPLC retention time: 2.80 min (analysis condition F)

Example 584

Compound S1-3

3-Chloro-4-fluoro-8-methoxy-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one

[3269] ##STR00599##

[3270] According to the same method as the method for synthesizing Compound A3-1, the title compound was prepared from Compound A2 and (3-chloro-2-fluoro-phenyl)-hydrazine.

[3271] LCMS: m/z 344, 346 [M+H].sup.+

[3272] HPLC retention time: 2.68 min (analysis condition S)

Example 585

Compound S1-4

9-Bromo-3-chloro-8-methoxy-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one

[3273] ##STR00600##

[3274] 6-Bromo-7-methoxy-1,1-dimethyl-3,4-dihydro-1H-naphthalen-2-one (Compound E1, 0.2 g, 0.71 mmol) and 3-chlorophenylhydrazine hydrochloric acid salt (0.17 g, 1.3 eq.) were dissolved in acetic acid (0.5 mL). Under nitrogen atmosphere, the reaction solution was stirred at 90 C. for 8 hr. After cooling to room temperature, the reaction solution was added with ethyl acetate, washed with water, saturated aqueous solution of sodium hydrogen carbonate and saturated brine and dried over magnesium sulfate. After filtration and concentration under reduced pressure, the residues obtained therefrom were dissolved in THF (3 mL) comprising 10% water, added with DDQ (227 mg, 3 eq.) at room temperature, and the mixture was stirred at room temperature for 2 hr. The reaction solution was added with the mixture liquid of THF/diethyl ether (1:1) and washed with 0.5 N aqueous solution of sodium hydroxide and saturated brine. After drying with sodium sulfate, the mixture was filtered and the resulting residues obtained after concentration under reduced pressure were washed with the mixture liquid of hexane/diethyl ether (1:1) to obtain the title compound (brown powder, 86 mg).

[3275] LCMS: m/z 404, 406, 408 [M+H].sup.+

[3276] HPLC retention time: 3.02 min (analysis condition C)

Example 586

Compound S2-1

3-Chloro-8-hydroxy-6,6-dimethyl-5,6-dihydrobenzo[b]carbazol-11-one

[3277] ##STR00601##

[3278] Under the same conditions as the method for synthesizing Compound A6, the title compound was prepared from Compound S1-1.

[3279] LCMS: m/z 312 [M+H].sup.+

[3280] HPLC retention time: 4.18 min (analysis condition H)

Example 587

Compound S2-2

3-Chloro-8-hydroxy-2,6,6-trimethyl-5,6-dihydro-benzo[b]carbazol-11-one

[3281] ##STR00602##

[3282] 3-Chloro-8-methoxy-2,6,6-trimethyl-5,6-dihydro-benzo[b]carbazol-11-one (Compound S1-2, 18.9 mg, 0.0556 mmol) and pyridinium chloride (220 mg, 34 eq.) were stirred at 185 C. for 2.5 hr. After cooling, the reaction solution was added with water and ethyl acetate, and the organic layer was washed with water and saturated brine, dried over magnesium sulfate, filtered and concentrated under reduced pressure to obtain the title compound as a crude product.

Example 588

Compound S2-3

3-Chloro-4-fluoro-8-hydroxy-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one

[3283] ##STR00603##

[3284] 3-Chloro-4-fluoro-8-methoxy-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one (Compound S1-3, 220.0 mg, 0.640 mmol) and pyridinium chloride (800 mg, 6.922 mmol) were mixed with each other, heated to 160 C., and then stirred for 20 hr. The reaction solution was added with water. As a result, black solid was obtained as a precipitate, which was then filtered and subjected to purification by silica gel column chromatography (ethyl acetate/hexane) to obtain the title compound (139.4 mg, 66%).

[3285] LCMS: m/z 330 [M+H].sup.+

[3286] HPLC retention time: 2.60 min (analysis condition F)

Example 589

Compound S2-4

9-Bromo-3-chloro-8-hydroxy-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one

[3287] ##STR00604##

[3288] Under the same conditions as the method for synthesizing Compound A6, the title compound was prepared from Compound S1-4.

[3289] LCMS: m/z 390, 392, 394 [M+H].sup.+

[3290] HPLC retention time: 2.75 min (analysis condition C)

Example 590

Compound S3

3-Chloro-8-(2-diethylaminoethoxy)-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one (CH5263231-000)

[3291] ##STR00605##

[3292] 3-Chloro-8-hydroxy-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one (Compound S2-1, 10 mg, 0.03207 mmol) was dissolved in DMF (0.1 mL), added with (2-chloroethyl)diethylamine (5.5 mg, 0.03207 mmol) and cesium carbonate (20.9 mg, 0.06414 mmol), and stirred at 80 C. for 2 hr. The reaction solution was added to water and extracted with ethyl acetate. The organic layer was dried over magnesium sulfate. The residues obtained after concentration under reduced pressure were purified by NH silica gel column chromatography (ethyl acetate/hexane) to obtain the title compound (11.6 mg, 76%).

[3293] LCMS: m/z 411 [M+H].sup.+

[3294] HPLC retention time: 4.49 min (analysis condition H)

Example 591

Compound S4

3-Chloro-2,6,6-trimethyl-8-((2R,3R)-2,3,4-trihydroxy-butoxy)-5,6-dihydro-benzo[b]carbazol-11-one

[3295] ##STR00606##

[3296] Crude product of Compound S2-2 was dissolved in THF (0.4 mL) under nitrogen atmosphere, together with THF (0.2 mL) solution of triphenylphosphine (18.9 mg, 1.3 eq.) and [(4R,5R)-5-(tert-butyl-dimethyl-silanyloxymethyl)-2,2-dimethyl-[1,3]dioxolan-4-yl]-methanol (17 mg, 1.2 eq.). DEAD (40% toluene solution, 0.0031 mL, 1.2 eq.) was added to the solution, which was then stirred at room temperature for 40 min and at 40 C. for 4 hr. The reaction solution was added with triphenylphosphine (18.9 mg, 1.3 eq.) and DEAD (40% toluene solution, 0.002 mL, 0.8 eq.) and stirred at 40 C. overnight. The reaction solution was added with ethyl acetate, washed with water and saturated brine, dried over magnesium sulfate, and filtered. The residues obtained after concentration under reduced pressure were purified by praparative TLC (ethyl acetate/hexane) to obtain the crude product of 8-[(4R,5R)-5-(tert-butyl-dimethyl-silanyloxymethyl)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy]-3-chloro-2,6,6-trimethyl-5,6-dihydro-benzo[b]carbazol-11-one (12.6 mg).

[3297] The resultant was dissolved in THF (0.15 mL) and methanol (0.03 mL) under nitrogen atmosphere, added with 0.5 M sulfuric acid (0.05 mL) and stirred at 60 C. for 3 hr. After cooling, diethyl ether was added and sodium hydrogen carbonate (8.4 mg) and water were further added thereto. The organic layer was washed with saturated brine. The aqueous layer was extracted with ethyl acetate, and the combined organic layer was dried over magnesium sulfate, and filtered. The solid obtained from the concentration under reduced pressure was washed with dichloromethane to obtain the target compound (white solid, 5.3 mg, 22%).

[3298] .sup.1H-NMR (400 MHz, DMSO-d.sub.6) : 12.18 (1H, s), 8.14 (1H, d, J=8.8 Hz), 8.12 (1H, s), 7.52 (1H, s), 7.31 (1H, d, J=2.4 Hz), 7.06 (1H, dd, J=2.4, 8.8 Hz), 4.78 (1H, d, J=5.9 Hz), 4.60 (1H, d, J=5.9 Hz), 4.52 (1H, t, J=5.4 Hz), 4.18-4.22 (1H, m), 4.02-4.06 (1H, m), 3.85-3.95 (1H, m), 3.50-3.60 (2H, m), 3.40-3.46 (1H, m), 2.45 (3H, s), 1.73 (3H, s),

[3299] LCMS: m/z 430 [M+H].sup.+

[3300] HPLC retention time: 2.27 min (analysis condition F)

Example 592

Compound S5

3-Chloro-8-ethoxy-4-fluoro-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one

[3301] ##STR00607##

[3302] The title compound was obtained as a by-product of the synthesis of Compound S6.

[3303] LCMS: m/z 358 [M+H].sup.+

[3304] HPLC retention time: 3.16 min (analysis condition F)

Example 593

Compound S6

3-Chloro-8-((R)-2,3-dihydroxy-propoxy)-4-fluoro-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one

[3305] ##STR00608##

[3306] 3-Chloro-4-fluoro-8-hydroxy-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one (Compound S2-3, 20.0 mg, 0.061 mmol) was dissolved in THF (0.25 mL), added with ((S)-2,2-dimethyl-[1,3]dioxolan-4-yl)-methanol (9.8 L, 0.079 mmol), triphenylphosphine (20.7 mg, 0.079 mmol) and diethyl azodicarboxylic acid (35.9 l, 0.079 mmol), and then stirred at 40 C. for 5 hr. The reaction solution was concentrated under reduced pressure, and the resulting residues were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain the intermediate, 3-chloro-8-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy)-4-fluoro-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one. This compound was dissolved in THF (0.10 mL) and MeOH (0.08 ml), added with sulfuric acid (0.5 M, 0.045 ml), and then stirred at 60 C. for 1 hr. The reaction solution was added with saturated aqueous solution of sodium hydrogen carbonate, extracted with ethyl acetate and dried over anhydrous magnesium sulfate. The yellow solid obtained after concentration under reduced pressure was washed with methylene chloride/hexane solvent and filtered to obtain the title compound (4.3 mg, 18%).

[3307] LCMS: m/z 404 [M+H].sup.+

[3308] HPLC retention time: 2.34 min (analysis condition F)

Example 594

Compound S7-1

3-Chloro-9-bromo-8-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy)-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one

[3309] ##STR00609##

[3310] Under nitrogen atmosphere, 9-bromo-3-chloro-8-hydroxy-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one (Compound S2-4, 76 mg, 0.2 mmol) and triphenylphosphine (69 mg, 1.3 eq.) were added with THF (2 ml), and ((S)-2,2-dimethyl-[1,3]dioxolan-4-yl)-methanol (35 mg, 1.3 eq.) and 2.19 N toluene solution (118 L, 1.3 eq.) of diethyl azodicarboxylic acid were added dropwise thereto, followed by stirring at 50 C. for 2 hr. After cooling, the reaction solution was added with ethyl acetate, washed with brine, dried over sodium sulfate and filtered. The residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/dichloromethane) to give a solid, which was then washed with dichloromethane to obtain the title compound (brown powder, 53 mg).

[3311] LCMS: m/z 504, 506, 508 [M+H].sup.+

[3312] HPLC retention time: 3.17 min (analysis condition C)

Example 595

Compound S7-2

9-Bromo-3-chloro-8-((R)-2,3-dihydroxy-propoxy)-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one

[3313] ##STR00610##

[3314] 3-Chloro-9-bromo-8-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy)-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one (Compound S7-1, 56 mg, 0.11 mmol) was dissolved in methanol (5 mL), added with 1 N hydrochloric acid (0.2 ml), and stirred at 50 C. for 2 hr. After cooling, the reaction solution was concentrated under reduced pressure and the resulting residues were added with methanol to obtain a precipitated solid, which was then filtered to obtain the title compound (white powder, 26 mg).

[3315] LCMS: m/z 464, 466, 468 [M+H].sup.+

[3316] HPLC retention time: 2.77 min (analysis condition C)

Example 596

Compound S7-3

3-Chloro-9-bromo-8-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy)-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one

[3317] ##STR00611##

[3318] Under nitrogen atmosphere, 9-bromo-3-chloro-8-hydroxy-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one (Compound S2-4, 112 mg, 0.29 mmol) and triphenylphosphine (227 mg, 3 eq.) were added with THF (2 ml), and ((R)-2,2-dimethyl-[1,3]dioxolan-4-yl)-methanol (114 mg, 3 eq.) and 2.19 N toluene solution (0.4 mL, 3 eq.) of diethyl azodicarboxylic acid were added dropwise thereto, followed by stirring at 40 C. for 12 hr under nitrogen atmosphere. The residues obtained from the reaction solution after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/dichloromethane) to obtain the title compound (white powder, 100 mg).

[3319] LCMS: m/z 504, 506, 508 [M+H].sup.+

[3320] HPLC retention time: 3.15 min (analysis condition C)

Example 597

Compound S7-4

9-Bromo-3-chloro-8-((S)-2,3-dihydroxy-propoxy)-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one

[3321] ##STR00612##

[3322] Under the same conditions as the method for synthesizing Compound S7-2, the title compound was prepared from Compound S7-3.

[3323] LCMS: m/z 464, 466, 468 [M+H].sup.+

[3324] HPLC retention time: 2.77 min (analysis condition C)

Example 598

Compound S8-1

9-Hydroxy-3-chloro-8-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy)-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one

[3325] ##STR00613##

[3326] 9-Bromo-3-chloro-8-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy)-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one (Compound S7-1, 30 mg, 0.06 mmol) was dissolved in the mixture solvent of waterdioxane (1:1) (0.5 mL), added with tris(benzylidenacetone dipalladium)chloroform complex (3.1 mg, 0.05 eq.), 2-di-tert-butylphosphino-2,4,6-triisopropylbiphenyl (2.5 mg, 0.1 eq.) and KOH (0.5 N aqueous solution 180 L, 1.5 eq.), and stirred at 60 C. for 12 hr. After cooling, the reaction solution was concentrated under reduced pressure, and the resulting residues were purified by HPLC to obtain the title compound (white solid, 4.6 mg).

[3327] LCMS: m/z 442, 444 [M+H]

[3328] HPLC retention time: 2.78 min (analysis condition C)

Example 599

Compound S8-2

3-Chloro-8-((R)-2,3-dihydroxy-propoxy)-9-hydroxy-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one

[3329] ##STR00614##

[3330] Under the same conditions as the method for synthesizing Compound S7-2, the title compound was prepared from Compound S8-1.

[3331] LCMS: m/z 402, 404 [M+H]

[3332] HPLC retention time: 0.90 min (analysis condition I)

Example 600

Compound S9-1

8-Hydroxy-6,6-dimethyl-11-oxo-9-(1H-tetrazol-5-yl)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[3333] ##STR00615##

[3334] 9-Bromo-3-chloro-8-methoxy-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one (Compound S1-4, 150 mg, 0.37 mMol) was dissolved in NMP, added with CuCN (100 mg, 3 eq.), and stirred at 210 C. for 1.5 hr under irradiation with microwave. After cooling, the reaction solution was added with water and ethyl acetate, and the precipitated solid was filtered to remove the solvent. The obtained residues were dissolved in DMF (1 ml), added with sodium azide (100 mg, 8 eq.) and ammonium chloride (5 mg), and then stirred at 120 C. for 24 hr in a sealed tube. After adding water, the insoluble matters were filtered and purified by HPLC to obtain the title compound (6.5 mg).

[3335] LCMS: m/z 371 [M+H].sup.+

[3336] HPLC retention time: 2.22 min (analysis condition C)

Example 601

Compound S9-2

3-Chloro-8-hydroxy-6,6-dimethyl-9-(1H-tetrazol-5-yl)-5,6-dihydro-benzo[b]carbazol-11-one

[3337] ##STR00616##

[3338] The title compound was obtained as an intermediate for the synthesis of Compound S9-1

[3339] LCMS: m/z 380, 382 [M+H].sup.+

[3340] HPLC retention time: 2.38 min (analysis condition C)

Example 602

Compound S10

3-Chloro-8-((R)-2,3-dihydroxy-propoxy)-9-(3-hydroxy-3-methyl-but-1-ynyl)-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one

[3341] ##STR00617##

[3342] To the mixture of 9-bromo-3-chloro-8-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy)-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-1-one (Compound S7-1, 50 mg, 0.1 mmol), bis(acetonitrile) palladium (II) dichloride (2.6 mg, 0.01 eq.), cesium carbonate (195 mg, 6 eq.) and 2-dicyclohexylphosphino-2,4,6-triisopropylbiphenyl (14.3 mg, 0.03 eq.), acetonitrile (2 mL) was added and stirred at 80 C. for 12 hr. Tar-like residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain 3-chloro-8-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy)-9-(3-hydroxy-3-methyl-but-1-ynyl)-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one (brown powder, 105 mg).

[3343] The resulting 3-chloro-8-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy)-9-(3-hydroxy-3-methyl-but-1-ynyl)-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one (20 mg, 0.04 mmol) was dissolved in methanol (3 mL), added with 1 N hydrochloric acid (1 ml), and stirred at room temperature for 12 hr. After cooling, the reaction solution was concentrated under reduced pressure, and the resulting residues were washed with methylene chloride to obtain the title compound (pale yellow powder, 5.2 mg).

[3344] LCMS: m/z 468, 470 [M+H].sup.+

[3345] HPLC retention time: 2.70 min (analysis condition C)

Example 603

Compound S11-1

3-Chloro-8-((R)-2,3-dihydroxy-propoxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-9-carbonitrile

[3346] ##STR00618##

[3347] 3-Chloro-9-bromo-8-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy)-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one (Compound S7-2, 17 mg, 37 mol) was dissolved in DMA, added with CuCN (17 mg, 5 eq.), and stirred at 220 C. for 2 hr under irradiation with microwave. After cooling, the reaction solution was added with ethyl acetate, and the precipitated solid was filtered to remove the solvent. The resulting residues were purified by HPLC to obtain the title compound (4 mg).

[3348] LCMS: m/z 409, 411 [M+H].sup.+

[3349] HPLC retention time: 2.65 min (analysis condition C)

Example 604

Compound S11-2

3-Chloro-8-hydroxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-9-carbonitrile

[3350] ##STR00619##

[3351] The title compound was obtained as a by-product of the synthesis of Compound S11-1.

[3352] LCMS: m/z 337, 339 [M+H].sup.+

[3353] HPLC retention time: 2.35 min (analysis condition C)

Example 605

Compound T1-1

3-Bromo-6,6-dimethyl-8-[(R)-(tetrahydro-furan-3-yl) oxy]-5,6-dihydro-benzo[b]carbazol-11-one

[3354] ##STR00620##

[3355] According to the same method as the method for synthesizing Compound A7-1, the title compound was prepared from Compound A5-1 and (S)-tetrahydro-furan-3-ol.

[3356] LCMS: m/z 426 [M+H].sup.+

[3357] HPLC retention time: 2.08 min (analysis condition D)

Example 606

Compound T1-2

6,6-Dimethyl-11-oxo-8-[(R)-(tetrahydro-furan-3-yl)oxy]-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[3358] ##STR00621##

[3359] According to the same method as the method for synthesizing Compound A5-2, the title compound was prepared from Compound T1-1.

[3360] LCMS: m/z 373 [M+H].sup.+

[3361] HPLC retention time: 1.98 min (analysis condition A)

Example 607

Compound T2-1

3-Bromo-6,6-dimethyl-8-[(S)-(tetrahydro-furan-3-yl)oxy]-5,6-dihydro-benzo[b]carbazol-11-one

[3362] ##STR00622##

[3363] According to the same method as the method for synthesizing Compound A7-1, the title compound was prepared from Compound A5-1 and (R)-tetrahydro-furan-3-ol.

[3364] LCMS: m/z 426 [M+H].sup.+

[3365] HPLC retention time: 6.12 min (analysis condition H)

Example 608

Compound T2-2

6,6-Dimethyl-11-oxo-8-[(S)-(tetrahydro-furan-3-yl)oxy]-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[3366] ##STR00623##

[3367] According to the same method as the method for synthesizing Compound A5-2, the title compound was prepared from Compound T2-1.

[3368] LCMS: m/z 373 [M+H].sup.+

[3369] HPLC retention time: 2.00 min (analysis condition D)

Example 609

Compound T3-1

3-Bromo-6,6-dimethyl-8-(tetrahydro-pyran-4-yl oxy)-5,6-dihydro-benzo[b]carbazol-11-one

[3370] ##STR00624##

[3371] According to the same method as the method for synthesizing Compound A7-1, the title compound was prepared from Compound A5-1 and tetrahydro-pyran-4-ol.

[3372] LCMS: m/z 440 [M+H].sup.+

[3373] HPLC retention time: 8.07 min (analysis condition H)

Example 610

Compound T3-2

3-Bromo-5,6,6-trimethyl-8-(tetrahydro-pyran-4-yl oxy)-5,6-dihydro-benzo[b]carbazol-11-one

[3374] ##STR00625##

[3375] According to the same method as the method for synthesizing Compound A10-2, the title compound was prepared from Compound T3-1.

[3376] LCMS: m/z 454 [M+H].sup.+

[3377] HPLC retention time: 6.88 min (analysis condition H)

Example 611

Compound T4-1

3-Bromo-6,6-dimethyl-8-(2-phenyl-[1,3]dioxan-5-yl oxy)-5,6-dihydro-benzo[b]carbazol-11-one

[3378] ##STR00626##

[3379] According to the same method as the method for synthesizing Compound A7-1, the title compound was prepared from Compound A5-1 and 5-phenyl-[1,3]dioxan-2-ol.

[3380] LCMS: m/z 518 [M+H].sup.+

[3381] HPLC retention time: 2.68 min (analysis condition D)

Example 612

Compound T4-2

3-Bromo-8-(2-hydroxy-1-hydroxymethyl-ethoxy)-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one

[3382] ##STR00627##

[3383] According to the same method as the method for synthesizing Compound A7-13-2, the title compound was prepared from Compound T4-1.

[3384] LCMS: m/z 430 [M+H].sup.+

[3385] HPLC retention time: 4.64 min (analysis condition H)

Example 613

Compound T5-1

4-(3-Bromo-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-8-yl oxy)-piperidine-1-carboxylic Acid Tert-Butyl Ester

[3386] ##STR00628##

[3387] According to the same method as the method for synthesizing Compound A7-1, the title compound was prepared from Compound A5-1 and 4-hydroxy-piperidine-1-carboxylic acid tert-butyl ester.

[3388] LCMS: m/z 539 [M+H].sup.+

[3389] HPLC retention time: 2.72 min (analysis condition D)

Example 614

Compound T5-2

4-(3-Bromo-5,6,6-trimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-8-yl oxy)-piperidine-1-carboxylic Acid Tert-Butyl Ester

[3390] ##STR00629##

[3391] According to the same method as the method for synthesizing Compound A10-1, the title compound was prepared from Compound T5-1.

[3392] LCMS: m/z 553 [M+H].sup.+

[3393] HPLC retention time: 2.93 min (analysis condition D)

Example 615

Compound T5-3

3-Bromo-5,6,6-trimethyl-8-(piperidin-4-yloxy)-5,6-dihydro-benzo[b]carbazol-11-one

[3394] ##STR00630##

[3395] According to the same method as the method for synthesizing Compound A8-1, the title compound was prepared from Compound T5-2.

[3396] LCMS: m/z 453 [M+H].sup.+

[3397] HPLC retention time: 1.98 min (analysis condition D)

Example 616

Compound T5-4

3-Bromo-8-(1-methanesulfonyl-piperidin-4-yloxy)-5,6,6-trimethyl-5,6-dihydro-benzo[b]carbazol-11-one

[3398] ##STR00631##

[3399] According to the same method as the method for synthesizing Compound A9-7, the title compound was prepared from Compound T5-3 and methanesulfonyl chloride.

[3400] LCMS: m/z 531 [M+H].sup.+

[3401] HPLC retention time: 2.38 min (analysis condition D)

Example 617

Compound T5-5

8-(1-Acetyl-piperidin-4-yloxy)-3-bromo-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one

[3402] ##STR00632##

[3403] According to the same method as the method for synthesizing Compound A9-1, the title compound was prepared from Compound T5-3 and acetic anhydride.

[3404] LCMS: m/z 482 [M+H].sup.+

[3405] HPLC retention time: 2.10 min (analysis condition D)

Example 618

Compound T6-1

3-Bromo-6,6-dimethyl-8-[1-(2,2,2-trifluoro-acetyl)-piperidin-4-yloxy]-5,6-dihydro-benzo[b]carbazol-11-one

[3406] ##STR00633##

[3407] According to the same method as the method for synthesizing Compound A9-1, the title compound was prepared from Compound T6-2 and trifluoroacetic anhydride.

[3408] LCMS: m/z 535 [M+H].sup.+

[3409] HPLC retention time: 2.53 min (analysis condition D)

Example 619

Compound T6-2

3-Bromo-6,6-dimethyl-8-(piperidin-4-yloxy)-5,6-dihydro-benzo[b]carbazol-11-one

[3410] ##STR00634##

[3411] 3-Bromo-6,6-dimethyl-8-[1-(2,2,2-trifluoro-acetyl)-piperidin-4-yloxy]-5,6-dihydro-benzo[b]carbazol-11-one (Compound T6-1, 28.0 mg, 52.3 mol) was dissolved in THF (1.00 mL) and methanol (0.50 mL), added with aqueous solution of potassium hydroxide (1.00 mL, 20 wt %), and stirred at room temperature for 1 hr. The reaction solution was added to water, and extracted with mixture solution of chloroform and methanol, and dried over sodium sulfate. Then, after filtering and concentration under reduced pressure, 3-bromo-6,6-dimethyl-8-(piperidin-4-yloxy)-5,6-dihydro-benzo[b]carbazol-11-one was obtained as a crude product.

[3412] LCMS: m/z 439 [M+H].sup.+

[3413] HPLC retention time: 1.83 min (analysis condition D)

Example 620

Compound T6-3

3-Bromo-8-(1-methanesulfonyl-piperidin-4-yloxy)-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one

[3414] ##STR00635##

[3415] According to the same method as the method for synthesizing Compound A9-1, the title compound was prepared from Compound T6-2 and mesyl chloride.

[3416] LCMS: m/z 517 [M+H].sup.+

[3417] HPLC retention time: 2.23 min (analysis condition D)

Example 621

Compound T6-4

8-(1-Acetyl-piperidin-4-yloxy)-3-bromo-5,6,6-trimethyl-5,6-dihydro-benzo[b]carbazol-11-one

[3418] ##STR00636##

[3419] According to the same method as the method for synthesizing Compound A9-1, the title compound was prepared from Compound T6-2 and acetic anhydride.

[3420] LCMS: m/z 496 [M+H].sup.+

[3421] HPLC retention time: 2.27 min (analysis condition D)

Example 622

Compound T7-1

3-Bromo-8-isopropoxy-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one

[3422] ##STR00637##

[3423] The title compound was obtained as a by-product of the synthesis of Compound T4-1.

[3424] LCMS: m/z 398 [M+H].sup.+

[3425] HPLC retention time: 3.18 min (analysis condition F)

Example 623

Compound T7-2

3-Bromo-8-isopropoxy-5,6,6-trimethyl-5,6-dihydro-benzo[b]carbazol-11-one

[3426] ##STR00638##

[3427] According to the same method as the method for synthesizing Compound A10-2, the title compound was prepared from Compound T7-1.

[3428] LCMS: m/z 413 [M+H].sup.+

[3429] HPLC retention time: 2.70 min (analysis condition D)

Example 624

Compound T8-1

3-Bromo-5,6,6-trimethyl-8-(2-phenyl-[1,3] dioxan-5-yl oxy)-5,6-dihydro-benzo[b]carbazol-11-one

[3430] ##STR00639##

[3431] According to the same method as the method for synthesizing Compound A10-2, the title compound was prepared from Compound T4-1.

[3432] LCMS: m/z 532 [M+H].sup.+

[3433] HPLC retention time: 2.90 min (analysis condition D)

Example 625

Compound T8-2

3-Bromo-8-(2-hydroxy-1-hydroxymethyl-ethoxy)-5,6,6-trimethyl-5,6-dihydro-benzo[b]carbazol-11-one

[3434] ##STR00640##

[3435] According to the same method as the method for synthesizing Compound A7-13-2, the title compound was prepared from Compound T4-1.

[3436] LCMS: m/z 444 [M+H].sup.+

[3437] HPLC retention time: 1.90 min (analysis condition D)

Example 626

Compound T9

N-[2-(3-Bromo-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-8-yl oxy)-ethyl]-acetamide

[3438] ##STR00641##

[3439] According to the same method as the method for synthesizing Compound A7-17, the title compound was prepared from Compound A5-1 and (N-(2-chloro-ethyl)-acetamide.

[3440] LCMS: m/z 441 [M+H].sup.+

[3441] HPLC retention time: 1.92 min (analysis condition D)

Example 627

Compound T10

3-Bromo-6,6-dimethyl-8-(oxetan-3-yl oxy)-5,6-dihydro-benzo[b]carbazol-11-one

[3442] ##STR00642##

[3443] According to the same method as the method for synthesizing Compound A7-17, the title compound was prepared from Compound A5-1 and toluene-4-sulfonic acid oxetan-3-yl ester.

[3444] LCMS: m/z 412 [M+H].sup.+

[3445] HPLC retention time: 2.17 min (analysis condition D)

Example 628

Compound T11

3-Bromo-8-(4-hydroxy-tetrahydro-furan-3-yl oxy)-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one

[3446] ##STR00643##

[3447] Under nitrogen atmosphere, tetrahydro-furo[3,4-d] [1,3,2]dioxathiol 2,2-dioxide (71.5 mg, 0.420 mmol) was dissolved in DMF (1.40 mL), added with 3-bromo-8-hydroxy-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one (Compound A5-1, 50.0 mg, 0.140 mmol) and cesium carbonate (228 mg, 0.700 mmol), and stirred at 80 C. for 15 hr. Subsequently, sulfuric acid (0.10 mL, 18 M), THF (3.00 mL) and water (0.50 mL) were added to the mixture, which was then stirred at room temperature for 24 hr and further at 60 C. for 24 hr. The reaction solution was added to water, extracted with ethyl acetate, washed with water, saturated aqueous solution of sodium bicarbonate, and saturated brine, and dried over sodium sulfate. After filtering and concentration under reduced pressure, the resulting residues were washed with dichloromethane and purified by NH silica gel column chromatography (ethyl acetate/THF) to obtain the target compound (44.7 mg, 72%).

[3448] LCMS: m/z 442 [M+H].sup.+

[3449] HPLC retention time: 1.98 min (analysis condition D)

Example 629

Compound T12-1

Acetic acid (2S,3R,4S,5R,6R)-4,5-diacetoxy-6-(3-bromo-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-8-yl oxymethyl)-2-methoxy-tetrahydro-pyran-3-yl Ester

[3450] ##STR00644##

[3451] According to the same method as the method for synthesizing Compound A7-1, the title compound was prepared from Compound A5-1 and methyl 2,3,4-tri-O-acetyl--D-glucopyranoside.

[3452] LCMS: m/z 658 [M+H].sup.+

[3453] HPLC retention time: 2.38 min (analysis condition D)

Example 630

Compound T12-2

3-Bromo-6,6-dimethyl-8-((2R,3S,4S,5R,6S)-3,4,5-trihydroxy-6-methoxy-tetrahydro-pyran-2-yl methoxy)-5,6-dihydro-benzo[b]carbazol-11-one

[3454] ##STR00645##

[3455] Under nitrogen atmosphere, to acetic acid (2S,3R,4S,5R,6R)-4,5-diacetoxy-6-(3-bromo-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-8-yl oxymethyl)-2-methoxy-tetrahydro-pyran-3-yl ester (Compound T12-1, 34.0 mg, 51.63 mol), methanol solution (2.50 mL, 2 M) of ammonia was added, and the mixture was stirred at room temperature for 21 hr. The reaction solution was concentrated under reduced pressure, and the resulting resides were washed with diethyl ether to obtain the target compound (25.7 mg, 94%).

[3456] LCMS: m/z 532 [M+H].sup.+

[3457] HPLC retention time: 2.42 min (analysis condition D)

Example 631

Compound T13-1

(3-Bromo-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-8-yl oxy)-acetic Acid Tert-Butyl Ester

[3458] ##STR00646##

[3459] According to the same method as the method for synthesizing Compound A7-17, the title compound was prepared from Compound A5-1 and bromo-acetic acid tert-butyl ester.

[3460] LCMS: m/z 470 [M+H].sup.+

[3461] HPLC retention time: 2.53 min (analysis condition D)

Example 632

Compound T13-2

(3-Bromo-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-8-yl oxy)-acetic Acid

[3462] ##STR00647##

[3463] According to the same method as the method for synthesizing Compound A8-1, the title compound was prepared from Compound T13-1.

[3464] LCMS: m/z 414 [M+H].sup.+

[3465] HPLC retention time: 1.50 min (analysis condition D)

Example 633

Compound T13-3

2-(3-Bromo-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-8-yl oxy)-N-(3-ethyl-3-hydroxy-pentyl)-acetamide

[3466] ##STR00648##

[3467] Under nitrogen atmosphere, (3-azide-1,1-diethyl-propoxy)-trimethyl-silane (16.6 mg, 72.42 mol) was dissolved in toluene (0.48 mL), added with 3-bromo-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-8-yl oxy)-acetic acid (20.0 mg, 48.28 mol) and Molecular Sieves 4 angstrom, and the mixture was stirred at room temperature for 5 min. Thereafter, the mixture was added with trimethylphosphine (10.2 L, 96.56 mol) and stirred at 80 C. for 22 hr. The reaction solution was added to hydrochloric acid (1 M), extracted with ethyl acetate, washed with water, saturated aqueous solution of sodium bicarbonate, saturated brine and dried over sodium sulfate. After filtering and concentration under reduced pressure, the resulting residues were purified by silica gel column chromatography (methanol/dichloromethane) to obtain the target compound (0.7 mg, 3%).

[3468] LCMS: m/z 527 [M+H].sup.+

[3469] HPLC retention time: 2.93 min (analysis condition D)

Example 634

Compound T13-4

4-[2-(3-Bromo-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-8-yl oxy)-acetyl]-piperazine-1-carboxylic Acid Tert-Butyl Ester

[3470] ##STR00649##

[3471] According to the same method as the method for synthesizing Compound A9-10, the title compound was prepared from Compound T13-2 and 1-(tert-butoxy carbonyl)piperazine.

[3472] LCMS: m/z 582 [M+H].sup.+

[3473] HPLC retention time: 2.32 min (analysis condition D)

Example 635

Compound T13-5

3-Bromo-6,6-dimethyl-8-(2-oxo-2-piperazin-1-yl-ethoxy)-5,6-dihydro-benzo[b]carbazol-11-one Hydrochloric Acid Salt

[3474] ##STR00650##

[3475] According to the same method as the method for synthesizing Compound A8-1, the title compound was prepared from Compound T13-4.

[3476] LCMS: m/z 482 [M+H].sup.+

[3477] HPLC retention time: 1.75 min (analysis condition D)

Example 636

Compound T13-6

3-Bromo-8-[2-(4-methanesulfonyl-piperazin-1-yl)-2-oxo-ethoxy]-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one

[3478] ##STR00651##

[3479] According to the same method as the method for synthesizing Compound A9-1, the title compound was prepared from Compound T13-5 and methanesulfonyl chloride.

[3480] LCMS: m/z 560 [M+H].sup.+

[3481] HPLC retention time: 2.00 min (analysis condition D)

Example 637

Compound T13-7

3-Bromo-6,6-dimethyl-8-{2-oxo-2-[4-(propane-2-sulfonyl)-piperazin-1-yl]-ethoxy}-5,6-dihydro-benzo[b]carbazol-11-one

[3482] ##STR00652##

[3483] According to the same method as the method for synthesizing Compound A9-1, the title compound was prepared from Compound T13-5 and isopropylsulfonyl chloride.

[3484] LCMS: m/z 588 [M+H].sup.+

[3485] HPLC retention time: 2.47 min (analysis condition D)

Example 638

Compound T13-8

8-[2-(4-Acetyl-piperazin-1-yl)-2-oxo-ethoxy]-3-bromo-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one

[3486] ##STR00653##

[3487] According to the same method as the method for synthesizing Compound A9-1, the title compound was prepared from Compound T13-5 and acetic anhydride.

[3488] LCMS: m/z 524 [M+H].sup.+

[3489] HPLC retention time: 1.85 min (analysis condition D)

Example 639

Compound T13-9

3-Bromo-6,6-dimethyl-8-[2-(4-oxetan-3-yl-piperazin-1-yl)-2-oxo-ethoxy]-5,6-dihydro-benzo[b]carbazol-11-one

[3490] ##STR00654##

[3491] According to the same method as the method for synthesizing Compound B3-32, the title compound was prepared from Compound T13-5 and 3-oxetanone.

[3492] LCMS: m/z 538 [M+H].sup.+

[3493] HPLC retention time: 1.88 min (analysis condition D)

Example 640

Compound T13-10

4-[2-(3-Bromo-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-8-yl-oxy)-acetyl]-piperazine-1-sulfonic Acid Methylamide

[3494] ##STR00655##

[3495] According to the same method as the method for synthesizing Compound A9-1, the title compound was prepared from Compound T13-5 and 2-oxo-oxazolidine-3-sulfonic acid methylamide.

[3496] LCMS: m/z 575 [M+H].sup.+

[3497] HPLC retention time: 2.29 min (analysis condition A)

Example 641

Compound T14-1

4-(3-Bromo-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-8-yl oxymethyl)-piperidine-1-carboxylic Acid Tert-Butyl Ester

[3498] ##STR00656##

[3499] According to the same method as the method for synthesizing Compound A7-1, the title compound was prepared from Compound A5-1 and 1-(tert-butoxy carbonyl)-4- (hydroxy methyl)piperidine.

[3500] LCMS: m/z 553 [M+H].sup.+

[3501] HPLC retention time: 2.80 mm (analysis condition D)

Example 642

Compound T14-2

3-Bromo-6,6-dimethyl-8-(pipendin-4-ylmethoxy)-5.6-dihydro-benzo-[b]carbazol-11-one hydrochlonc acid salt

[3502] ##STR00657##

[3503] According to the same method as the method for synthesizing Compound A8-1, the title compound was prepared from Compound T14-1.

[3504] LCMS: m/z 454 [M+H].sup.+

[3505] HPLC retention time: 1.90 min (analysis condition D)

Example 643

Compound T14-3

3-Bromo-6,6-dimethyl-8-(1-oxetan-3-yl-piperidin-4-ylmethoxy)-5,6-dihydro-benzo[b]carbazol-11-one

[3506] ##STR00658##

[3507] According to the same method as the method for synthesizing Compound B3-32, the title compound was prepared from Compound T14-2 and 3-oxetanone.

[3508] .sup.1H-NMR (400 MHz, CDCl.sub.3) : 9.24 (1H, s), 8.37 (1H, d, 8.8 Hz), 8.30 (1H, d, 8.3 Hz), 7.57 (1H, d, 1.5 Hz), 7.41 (1H, dd, 8.3, 1.5 Hz), 7.08 (1H, d, 2.4 Hz), 6.98 (1H, dd, 8.8, 2.4 Hz) 4.60-4.95 (7H, m), 3.93 (2H, d, 5.9 Hz), 3.50 (1H, m), 2.83 (2H, d, 11.2 Hz), 1.89 (4H, m), 1.78 (6H, s),

[3509] LCMS: m/z 509 [M+H].sup.+

[3510] HPLC retention time: 2.10 min (analysis condition A)

Example 644

Compound T14-4

8-(1-Acetyl-piperidin-4-ylmethoxy)-3-bromo-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one

[3511] ##STR00659##

[3512] According to the same method as the method for synthesizing Compound A9-1, the title compound was prepared from Compound T14-2 and acetic anhydride.

[3513] LCMS: m/z 495 [M+H].sup.+

[3514] HPLC retention time: 2.53 min (analysis condition A)

Example 645

Compound T14-5

3-Bromo-8-(1-methanesulfonyl-piperidin-4-ylmethoxy)-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one

[3515] ##STR00660##

[3516] According to the same method as the method for synthesizing Compound A9-1, the title compound was prepared from Compound T14-2 and methanesulfonyl chloride.

[3517] LCMS: m/z 531 [M+H].sup.+

[3518] HPLC retention time: 2.30 min (analysis condition D)

Example 646

Compound T14-6

3-Bromo-6,6-dimethyl-8-[1-(propane-2-sulfonyl)-piperidin-4-ylmethoxy]-5,6-dihydro-benzo[b]carbazol-11-one

[3519] ##STR00661##

[3520] According to the same method as the method for synthesizing Compound A9-1, the title compound was prepared from Compound T14-2 and isopropylsulfonyl chloride.

[3521] LCMS: m/z 559 [M+H].sup.+

[3522] HPLC retention time: 2.58 min (analysis condition D)

Example 647

Compound T14-7

3-[4-(3-Bromo-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-8-yl oxymethyl)-piperidin-1-yl]-azetidine-1-carboxylic Acid Tert-Butyl Ester

[3523] ##STR00662##

[3524] According to the same method as the method for synthesizing Compound B3-32, the title compound was prepared from Compound T14-2 and 3-oxo-azetidine-1-carboxylic acid tert-butyl ester.

[3525] LCMS: m/z 608 [M+H].sup.+

[3526] HPLC retention time: 2.29 min (analysis condition A)

Example 648

Compound T14-8

8-(1-Azetidin-3-yl-piperidin-4-ylmethoxy)-3-bromo-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one

[3527] ##STR00663##

[3528] According to the same method as the method for synthesizing Compound A8-1, the title compound was prepared from Compound T14-7.

[3529] LCMS: m/z 508 [M+H].sup.+

[3530] HPLC retention time: 1.90 min (analysis condition A)

Example 649

Compound T14-9

3-Bromo-8-[1-(1-methanesulfonyl-azetidin-3-yl)-piperidin-4-ylmethoxy]-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one

[3531] ##STR00664##

[3532] According to the same method as the method for synthesizing Compound A9-1, the title compound was prepared from Compound T14-8 and mesyl chloride.

[3533] LCMS: m/z 586 [M+H].sup.+

[3534] HPLC retention time: 2.06 min (analysis condition A)

Example 650

Compound T14-10

8-[1-(1-Acetyl-azetidin-3-yl)-piperidin-4-ylmethoxy]-3-bromo-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one

[3535] ##STR00665##

[3536] According to the same method as the method for synthesizing Compound A9-1, the title compound was prepared from Compound T14-8 and acetic anhydride.

[3537] LCMS: m/z 550 [M+H].sup.+

[3538] HPLC retention time: 2.53 min (analysis condition A)

Example 651

Compound T15-1

4-[2-(3-Bromo-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-8-yl oxy)-ethyl]-piperidine-1-carboxylic Acid Tert-Butyl Ester

[3539] ##STR00666##

[3540] According to the same method as the method for synthesizing Compound A7-1, the title compound was prepared from Compound A5-1 and N-(tert-butoxycarbonyl)-4-piperidine ethanol.

[3541] LCMS: m/z 567 [M+H].sup.+

[3542] HPLC retention time: 2.29 min (analysis condition D)

Example 652

Compound T15-2

3-Bromo-6,6-dimethyl-8-(2-piperidin-4-yl-ethoxy)-5,6-dihydro-benzo[b]carbazol-11-one

[3543] ##STR00667##

[3544] According to the same method as the method for synthesizing Compound A8-1, the title compound was prepared from Compound T15-1.

[3545] LCMS: m/z 467 [M+H].sup.+

[3546] HPLC retention time: 1.95 min (analysis condition D)

Example 653

Compound T15-3

3-Bromo-6,6-dimethyl-8-[2-(1-oxetan-3-yl-piperidin-4-yl)-ethoxy]-5,6-dihydro-benzo[b]carbazol-11-one

[3547] ##STR00668##

[3548] According to the same method as the method for synthesizing Compound B3-32, the title compound was prepared from Compound T15-2 and 3-oxetanone.

[3549] LCMS: m/z 523 [M+H].sup.+

[3550] HPLC retention time: 2.28 min (analysis condition D)

Example 654

Compound T16-1

4-(3-Bromo-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-8-yl oxy)-1-oxa-8-aza-spiro[4.5]decane-8-carboxylic Acid Tert-Butyl Ester

[3551] ##STR00669##

[3552] According to the same method as the method for synthesizing Compound A7-1, the title compound was prepared from Compound A5-1 and 3-hydroxy-1-oxa-8-aza-spiro[4.5] decane-8-carboxylic acid tert-butyl ester.

[3553] LCMS: m/z 595 [M+H].sup.+

[3554] HPLC retention time: 3.08 min (analysis condition A)

Example 655

Compound T16-2

3-Bromo-6,6-dimethyl-8-(1-oxa-8-aza-spiro[4.5]decan-4-yl oxy)-5,6-dihydro-benzo[b]carbazol-11-one

[3555] ##STR00670##

[3556] According to the same method as the method for synthesizing Compound A8-1, the title compound was prepared from Compound T16-1.

[3557] LCMS: m/z 496 [M+H].sup.+

[3558] HPLC retention time: 1.99 min (analysis condition A)

Example 656

Compound T16-3

3-Bromo-8-(8-methanesulfonyl-1-oxa-8-aza-spiro[4.5]decan-4-yl oxy)-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one

[3559] ##STR00671##

[3560] According to the same method as the method for synthesizing Compound A9-1, the title compound was prepared from Compound T16-2 and mesyl chloride.

[3561] LCMS: m/z 573 [M+H].sup.+

[3562] HPLC retention time: 2.56 min (analysis condition A)

Example 657

Compound T16-4

3-Bromo-6,6-dimethyl-8-(8-oxetan-3-yl-1-oxa-8-aza-spiro[4.5]decan-4-yl oxy)-5,6-dihydro-benzo[b]carbazol-11-one

[3563] ##STR00672##

[3564] According to the same method as the method for synthesizing Compound B3-32, the title compound was prepared from Compound T16-2 and 3-oxetanone.

[3565] LCMS: m/z 551 [M+H].sup.+

[3566] HPLC retention time: 2.01 min (analysis condition A)

Example 658

Compound T17-1

3,7,9-Tribromo-8-hydroxy-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one

[3567] ##STR00673##

[3568] Under nitrogen atmosphere, 4-[1,3]dithian-2-ylidene-piperidine-1-carboxylic acid tert-butyl ester (100 g, 0.332 mmol) was dissolved in dichloromethane (2.50 mL), added with trifluoromethanesulfonic acid (30.8 L, 0.348 mmol) at 20 C., and stirred at room temperature for 30 min. The reaction solution was cooled to 70 C., and then added dropwise with the dichloromethane (2.50 mL) solution of 3-bromo-8-hydroxy-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one (Compound A5-1, 177 mg, 0.498 mmol) and triethylamine (78.6 L, 0.564 mmol). Thereafter, triethylamine hydrotrifluoric acid salt (262 L, 1.610 mmol) and 1,3-dibromo-5,5-dimethylhydantoin (460 mg, 1.610 mmol) were added thereto and stirred at 70 C. for 1 hr. The reaction solution was added to aqueous solution of sodium hydroxide (1 M), extracted with ethyl acetate, washed with water, saturated aqueous solution of sodium bicarbonate, saturated brine and dried over sodium sulfate. After filtering and concentration under reduced pressure, the resulting residues were purified by silica gel column chromatography (ethyl acetate/hexane) and aminosilica gel column chromatography (ethyl acetate/hexane) to obtain the target compound (42.0 mg, 25%).

[3569] LCMS: m/z 511 [M+H].sup.+

[3570] HPLC retention time: 6.34 min (analysis condition B)

Example 659

Compound T17-2

3,7,9-Tribromo-8-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy)-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one

[3571] ##STR00674##

[3572] According to the same method as the method for synthesizing Compound A7-1, the title compound was prepared from Compound A17-1 and (S)-(+)-2,2-dimethyl-1,3-dioxolan-4-methanol.

[3573] LCMS: m/z 625 [M+H].sup.+

[3574] HPLC retention time: 3.41 min (analysis condition A)

Example 660

Compound T17-3

3,7,9-Tribromo-8-((R)-2,3-dihydroxy-propoxy)-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one

[3575] ##STR00675##

[3576] According to the same method as the method for synthesizing Compound A7-14-2, the title compound was prepared from Compound T17-2.

[3577] LCMS: m/z 585 [M+H].sup.+

[3578] HPLC retention time: 2.44 min (analysis condition A)

Example 661

Compound T18-1

3-Bromo-8-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy)-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one

[3579] ##STR00676##

[3580] 3-Bromo-8-hydroxy-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one (Compound A5-1, 18.0 mg, 50.5 mol) was dissolved in DMF (0.18 mL), added with toluene-4-sulfonic acid (R)-2,2-dimethyl-[1,3]dioxolan-4-yl methyl ester (14.5 mg, 0.0505 mmol) and potassium carbonate (10.0 mg, 0.07575 mmol), and the mixture was stirred at 70 C. for 3 days. The reaction solution was added to water, extracted with ethyl acetate, and the organic layer was dried over magnesium sulfate. The residues obtained after concentration under reduced pressure were purified by preparative TLC (methylene chloride/methanol) to obtain the title compound (16.6 mg, 70%).

[3581] LCMS: m/z 470 [M+H].sup.+

[3582] HPLC retention time: 3.01 min (analysis condition F)

Example 662

Compound T18-2

3-Bromo-8-((R)-2,3-dihydroxy-propoxy)-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one

[3583] ##STR00677##

[3584] Under the same conditions as the method for synthesizing Compound A7-14-2, the title compound was prepared from Compound T18-1.

[3585] LCMS: m/z 430 [M+H].sup.+

[3586] HPLC retention time: 4.72 min (analysis condition H)

Example 663

Compound T19-1-1

3-Bromo-8-methoxy-5,6,6-trimethyl-5,6-dihydro-benzo[b]carbazol-11-one

[3587] ##STR00678##

[3588] Under the same conditions as the method for synthesizing Compound A10-1, the title compound was prepared from Compound A4.

[3589] LCMS: m/z 384 [M+H].sup.+

[3590] HPLC retention time: 2.84 min (analysis condition D)

Example 664

Compound T19-1

3-Bromo-8-hydroxy-5,6,6-trimethyl-5,6-dihydro-benzo[b]carbazol-11-one

[3591] ##STR00679##

[3592] Under the same conditions as the method for synthesizing Compound A6, the title compound was prepared from Compound T19-1-1.

[3593] LCMS: m/z 370 [M+H].sup.+

[3594] HPLC retention time: 2.40 min (analysis condition D)

Example 665

Compound T19-2

3-Bromo-8-(2-diethylaminoethoxy)-6,6-trimethyl-5,6-dihydro-benzo[b]carbazol-11-one

[3595] ##STR00680##

[3596] Under the same conditions as the method for synthesizing Compound A7-17, the title compound was prepared from Compound A5-1 (9.8 mg, 36%).

[3597] LCMS: m/z 455 [M+H].sup.+

[3598] HPLC retention time: 1.96 min (analysis condition D)

Example 666

Compound T19-3

3-Bromo-8-(2-diethylaminoethoxy)-5,6,6-trimethyl-5,6-dihydro-benzo[b]carbazol-11-one

[3599] ##STR00681##

[3600] Under the same conditions as the method for synthesizing Compound A7-17, the title compound was prepared from Compound T19-1.

[3601] LCMS: m/z 469 [M+H].sup.+

[3602] HPLC retention time: 2.09 min (analysis condition D)

Example 667

Compound T20

5-(3-Bromo-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl oxy)-pentanoic Acid

[3603] ##STR00682##

[3604] Under the same conditions as the method for synthesizing Compound A7-17, Compound A5-1 and methyl 5-bromovalerate were reacted, added with 1 N NaOH (140 L), and then stirred at room temperature for 2 hr. The reaction mixture was added with 2 N HCl (70 L), and concentrated under reduced pressure. The resulting residues were purified by preparative TLC (methylene chloride:methanol=15:1) to obtain 7 mg (55%).

[3605] LCMS: m/z 456 [M+H].sup.+

[3606] HPLC retention time: 5.88 min (analysis condition H)

Example 668

Compound T21

(R)-5-(3-Bromo-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl oxy)-4-hydroxy-pentanoic Acid

[3607] ##STR00683##

[3608] Under the same conditions as the method for synthesizing Compound T20, the title compound was prepared from the reaction between Compound A5-1 and toluene-4-sulfonic acid (R)-5-oxo-tetrahydrofuran-2-yl methyl ester.

[3609] LCMS: m/z 471 [M+H].sup.+

[3610] HPLC retention time: 4.57 min (analysis condition H)

Example 669

Compound T22-0

[5-(Tert-butyldimethylsilanyloxymethyl)-2,2-dimethyl-[1,3]dioxolan-4-yl]-methanol

[3611] ##STR00684##

[3612] To THF (50 mL), NaH (1.41 g, 0.032 mmol) was added at room temperature, followed by addition of ((4R,5R)-5-hydroxymethyl-2,2-dimethyl-[1,3]dioxolan-4-yl)-methanol (5.0 g, 0.031 mmol) at room temperature. The mixture was stirred at room temperature for 1 hr. After that, TBSCl (5.11 g, 0.034 mmol) was added at room temperature and stirred at room temperature overnight. The reaction solution was added with saturated aqueous solution of sodium hydrogen carbonate and extracted with ethyl acetate. The organic layer was dried over magnesium sulfate. The residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain the title compound (8.21 g, 96%).

[3613] .sup.1H-NMR (270 MHz, DMSO-d.sub.6) : 3.64-4.98 (6H, m), 2.37 (1H, m), 1.41 (3H, s), 1.40 (3H, s), 0.90 (9H, s), 0.08 (6H, s)

Example 670

Compound T22-1

3-Bromo-8-[(4R,5R)-5-(tert-butyldimethylsilanyloxymethyl)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy]-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one

[3614] ##STR00685##

[3615] Under the same conditions as the method for synthesizing Compound A7-1, the title compound was prepared from Compound A5-1 and [5-(tert-butyldimethylsilanyloxymethyl)-2,2-dimethyl-[1,3]dioxolan-4-yl]-methanol (Compound T22-0) (704 mg, 80%).

[3616] LCMS: m/z 614 [M+H].sup.+

[3617] HPLC retention time: 4.00 min (analysis condition F)

Example 671

Compound T22-1-1

3-Bromo-8-((1R,5R)-5-hydroxymethyl-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy)-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one

[3618] ##STR00686##

[3619] Under nitrogen atmosphere, to the DMF (0.4 mL) suspension of 3-bromo-8-[(1R,5R)-5-(tert-butyl-dimethyl-silanyloxymethyl)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy]-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one (Compound T22-1, 50.3 mg, 0.0818 mmol) and copper (I) iodide (34 mg), sodium methoxide (1 M methanol solution, 0.82 mL, 0.818 mmol) was added and the mixture was stirred for 6 hr and 45 min at ambient temperature of 90 C. After cooling to room temperature, the reaction mixture was added with diethyl ether and ethyl acetate, and the insoluble matters were removed by Celite filtration. The concentrated residues were added with diethyl ether, hexane, ethyl acetate and water, and then the mixture was extracted twice with diethyl ether. The organic layer was washed with water and subsequently with brine, dried over sodium sulfate and concentrated under reduced pressure. The resulting crude product was purified by preparative TLC (Merck60 F.sub.254, 0.5 mm) {solution for elution: hexane/ethyl acetate (1:2)} to obtain the title compound (colorless oily substance, 22.6 mg, 55%).

[3620] .sup.1H-NMR (270 MHz, CDCl.sub.3) : 8.44-8.38 (1H, b), 8.39 (1H, d, 8.6 Hz), 8.31 (1H, d, 8.2 Hz), 7.60 (1H, d, 1.3 Hz), 7.44 (1H, dd, 8.2 Hz, 1.3 Hz), 7.12 (1H, d, 2.3 Hz), 7.02 (1H, dd, 8.6 Hz, 2.3 Hz), 4.41-4.10 (4H, m), 4.00-3.88 (1H, m), 3.86-3.76 (1H, m), 1.78 (6H, s), 1.50 (3H, s), 1.49 (3H, s)

[3621] LCMS: m/z 500 [M+H].sup.+

[3622] HPLC retention time: 2.85 min (analysis condition C)

Example 672

Compound T22-1-2

Acetic acid (3R,4R)-5-(3-bromo-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl oxymethyl)-2,2-dimethyl[1,3]dioxolan-4-yl methyl Ester

[3623] ##STR00687##

[3624] The title compound was obtained as a by-product of the synthesis of T22-1-1 (white solid, 17.8 mg, 40%).

[3625] .sup.1H-NMR (270 MHz, CDCl.sub.3) : 8.92-8.80 (1H, b), 8.40 (1H, d, 8.9 Hz), 8.31 (1H, d, 8.6 Hz), 7.58 (1H, d, 1.7 Hz), 7.43 (1H, dd, 8.6 Hz, 1.7 Hz), 7.14 (1H, d, 2.3 Hz), 7.02 (1H, dd, 8.9 Hz, 2.3 Hz), 4.51-4.38 (1H, m), 4.34-4.16 (4H, m), 2.13 (3H, s), 1.78 (6H, s), 1.50 (6H, s)

[3626] LCMS: m/z 542 [M+H].sup.+

[3627] HPLC retention time: 3.00 min (analysis condition C)

Example 673

Compound T22-2

3-Bromo-6,6-dimethyl-8-((2R,3R)-2,3,4-trihydroxy-butoxy)-5,6-dihydro-benzo[b]carbazol-11-one

[3628] ##STR00688##

[3629] Under the same conditions as the method for synthesizing Compound A7-14-2, the title compound was prepared from Compound T22-1 (2.83 g, 95%).

[3630] LCMS: m/z 460 [M+H].sup.+

[3631] HPLC retention time: 4.50 min (analysis condition H)

Example 674

Compound T22-3

3-Bromo-8-[(4R,5R)-5-(tert-butyldimethylsilanyloxymethyl)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy]-5,6,6-trimethyl-5,6-dihydro-benzo[b]carbazol-11-one

[3632] ##STR00689##

[3633] Under the same conditions as the method for synthesizing Compound B3-4, the title compound was prepared from Compound T22-1.

[3634] LCMS: m/z 628 [M+H].sup.+

[3635] HPLC retention time: 4.74 min (analysis condition F)

Example 675

Compound T22-4

3-Bromo-8-((2R,3R)-2,3-dihydroxy-pentyloxy)-5,6,6-trimethyl-5,6-dihydro-benzo[b]carbazol-11-one

[3636] ##STR00690##

[3637] Under the same conditions as the method for synthesizing Compound A7-14-2, the title compound was prepared from Compound T22-3.

[3638] LCMS: m/z 475 [M+H].sup.+

[3639] HPLC retention time: 4.86 min (analysis condition H)

Example 676

Compound T22-5

{3-Bromo-8-[(4R,5R)-5-(tert-butyldimethylsilanyloxymethyl)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy]-6,6-dimethyl-11-oxo-6,11-dihydro-benzo[b]carbazol-5-yl}-acetic Acid Methyl Ester

[3640] ##STR00691##

[3641] Under nitrogen atmosphere, 3-bromo-8-[(4R,5R)-5-(tert-butyldimethylsilanyloxymethyl)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy]-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one (Compound T22-1, 40.0 mg, 65.2 mol) was dissolved in DMF (0.20 mL), added at 0 C. with methyl bromoacetate (30.5 L, 134.5 mol) and sodium hydride (4.5 mg, 132 mol), and then stirred at room temperature for 2 hr. The residues obtained from the reaction solution after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain the title compound (44.5 mg, 85%).

[3642] LCMS: m/z 686 [M+H].sup.+

[3643] HPLC retention time: 3.35 min (analysis condition D)

Example 677

Compound T22-6

{3-Bromo-8-[(4R,5R)-5-(tert-butyldimethylsilanyloxymethyl)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy]-6,6-dimethyl-11-oxo-6,11-dihydro-benzo[b]carbazol-5-yl}-acetic Acid

[3644] ##STR00692##

[3645] {3-Bromo-8-[(4R,5R)-5-(tert-butyl-dimethyl-silanyloxymethyl)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy]-6,6-dimethyl-11-oxo-6,11-dihydro-benzo[b]carbazol-5-yl}-acetic acid methyl ester (Compound T22-5, 40 mg, 60.0 mol) was dissolved in the mixture solvent of methanol (120 l) and water (30 l), added with lithium hydroxide monohydrate (10 mg, 240 mol), and then stirred 40 C. for 15 min. The residues obtained from the reaction solution after concentration under reduced pressure were purified by silica gel column chromatography (methylene chloride/methanol) to obtain the target compound (35.2 mg, 96%).

[3646] LCMS: m/z 672 [M+H].sup.+

[3647] HPLC retention time: 3.41 min (analysis condition D)

Example 678

Compound T22-7

[3-Bromo-6,6-dimethyl-11-oxo-8-((2R,3R)-2,3,4-trihydroxy-butoxy)-6,11-dihydro-benzo[b]carbazol-5-yl]-acetic Acid

[3648] ##STR00693##

[3649] Under the same conditions as the method for synthesizing Compound A7-14-2, the title compound was prepared from Compound T22-6 (6.2 mg, 31%).

[3650] LCMS: m/z 518 [M+H].sup.+

[3651] HPLC retention time: 1.30 min (analysis condition D)

Example 679

Compound T22-8

[3-Bromo-6,6-dimethyl-11-oxo-8-((2R,3R)-2,3,4-trihydroxy-butoxy)-6,11-dihydro-benzo[b]carbazol-5-yl]-acetic Acid Methyl Ester

[3652] ##STR00694##

[3-Bromo-6,6-dimethyl-11-oxo-8-((2R,3R)-2,3,4-trihydroxy-butoxy)-6,11-dihydro-benzo[b]carbazol-5-yl]-acetic acid (Compound T22-6, 15.0 mg, 29.0 mol) was dissolved in methanol (0.30 mL), added with trimethylsilyldiazomethane (0.10 mL), and then stirred at room temperature for 1 hr. The residues obtained from the reaction solution after concentration under reduced pressure were purified by silica gel column chromatography (methylene chloride/methanol) to obtain the target compound (15.2 mg, 96%).

[3653] LCMS: m/z 532 [M+H].sup.+

[3654] HPLC retention time: 1.80 min (analysis condition D)

Example 680

Compound T23-1

3-Bromo-5-((R)-1,2-dihydroxyethyl)-8-methoxy-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one

[3655] ##STR00695##

[3656] Under the same conditions as the method for synthesizing Compound T18-1 and Compound T18-2, the title compound was prepared from Compound A5-1 and toluene-4-sulfonic acid (R)-2,2-dimethyl-[1,3]dioxolan-4-yl methyl ester.

[3657] LCMS: m/z 366 [M+H].sup.+

[3658] HPLC retention time: 4.50 min (analysis condition H)

Example 681

Compound T23-2

3-Bromo-5-((S)-1,2-dihydroxyethyl)-8-methoxy-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one

[3659] ##STR00696##

[3660] Under the same conditions as the method for synthesizing Compound T18-1 and Compound T18-2, the title compound was prepared from Compound A4 and toluene-4-sulfonic acid (S)-2,2-dimethyl-[1,3]dioxolan-4-yl methyl ester.

[3661] LCMS: m/z 366 [M+H].sup.+

[3662] HPLC retention time: 4.50 min (analysis condition H)

Example 682

Compound T24-1

3-Bromo-8-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy)-5,6,6-trimethyl-5,6-dihydro-benzo[b]carbazol-11-one

[3663] ##STR00697##

[3664] Under nitrogen atmosphere, to the DMF (1 mL) suspension of 3-bromo-8-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy)-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one (Compound T18-1, 112.2 mg, 0.239 mmol) and sodium hydride (60%) (19 mg, 0.477 mmol), cooled in an ice bath, methyl iodide (37 mL, 0.596 mmol) was added. The reaction mixture was stirred at room temperature for 45 min, and then added with saturated aqueous solution of ammonium chloride and saturated aqueous solution of sodium thiosulfate under ice cooling. The mixture was extracted twice with ethyl acetate/diethyl ether/hexane. The organic layer was washed with water and subsequently with aqueous solution of ammonium chloride, dried over sodium sulfate, and then concentrated under reduced pressure. The resulting crude product was purified by flash column chromatography {Merck Kieselgel60, solution for elution: hexane/ethyl acetate (1:1)} to obtain the title compound (white solid, 107.3 mg, 93%).

[3665] .sup.1H-NMR (270 MHz, CDCl.sub.3) : 8.41 (1H, d, 8.6 Hz), 8.35 (1H, d, 8.9 Hz), 7.56 (1H, d, 1.7 Hz), 7.46 (1H, dd, 8.6 Hz, 1.7 Hz), 7.14 (1H, d, 2.3 Hz), 7.00 (1H, dd, 8.9 Hz, 2.3 Hz), 4.60-4.49 (1H, m), 4.20-3.90 (4H, m), 4.03 (3H, s), 1.88 (6H, s), 1.50 (3H, s), 1.43 (3H, s)

[3666] LCMS: m/z 484 [M+H].sup.+

[3667] HPLC retention time: 6.59 min (analysis condition B)

Example 683

Compound T24-2

3-Bromo-8-((R)-2,3-dihydroxy-propoxy)-5,6,6-trimethyl-5,6-dihydro-benzo[b]carbazol-11-one

[3668] ##STR00698##

[3669] Under nitrogen atmosphere, to the THF (0.15 mL)-MeOH (0.1 mL) solution of 3-bromo-8-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy)-5,6,6-trimethyl-5,6-dihydro-benzo[b]carbazol-11-one (Compound T24-1, 15.5 mg, 0.0320 mmol), 0.5 M aqueous solution of sulfuric acid (128 L, 0.0640 mmol) was added at room temperature. The reaction mixture was stirred at ambient temperature of 55 C. for 2 hr, cooled to room temperature, and then added with diethyl ether and subsequently with sodium hydrogen carbonate (11 mg). The mixture was extracted twice with diethyl ether/ethyl acetate, and the organic layer was washed with brine, dried over sodium sulfate and concentrated under reduced pressure to obtain the title compound (white solid, 11.9 mg, 84%).

[3670] .sup.1H-NMR (270 MHz, CD.sub.3OD) : 8.26 (1H, d, 8.6 Hz), 8.20 (1H, d, 8.9 Hz), 7.77 (1H, d, 1.7 Hz), 7.42 (1H, dd, 8.6 Hz, 1.7 Hz), 7.33 (1H, d, 2.3 Hz), 7.09 (1H, dd, 8.9 Hz, 2.3 Hz), 4.26-3.96 (3H, m), 4.10 (3H, s), 3.74-3.66 (1H, m), 1.92 (6H, s)

[3671] LCMS: m/z 444 [M+H].sup.+

[3672] HPLC retention time: 4.65 min (analysis condition B)

Example 684

Compound T25

3-Bromo-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one

[3673] ##STR00699##

[3674] Under the same conditions as the method for synthesizing Compound A3-1 and Compound A4, the title compound was prepared from 3,4-dihydro-1H-naphthalen-2-one (560 mg).

[3675] LCMS: m/z 340 [M+H].sup.+

[3676] HPLC retention time: 4.57 min (analysis condition H)

Example 685

Compound T26-1

8-[(4R,5R)-5-(Tert-butyldimethylsilanyloxymethyl)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy]-3-iodo-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one

[3677] ##STR00700##

[3678] Under nitrogen atmosphere, 3-bromo-8-[(4R,5R)-5-(tert-butyldimethylsilanyloxymethyl)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy]-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one (Compound T22-1, 300 mg, 0.47 mmol), sodium iodide (147 mg, 0.94 mmol) and copper iodide (9.40 mg, 0.047 mmol) were dissolved in dioxane (1.00 ml), added with (1R,2R)N,N,N,N-tetramethyl-cyclohexane-1,2-diamine (15.4 l, 0.094 mmol), and then stirred at 110 C. for 16 hr. The residues obtained from the reaction solution after concentration under reduced pressure were purified by silica gel column chromatography (methylene chloride/methanol) to obtain the title compound (220 mg, 70%).

[3679] LCMS: m/z 662 [M+H].sup.+

[3680] HPLC retention time: 3.40 min (analysis condition D)

Example 686

Compound T26-2

3-Iodo-6,6-dimethyl-8-((2R,3R)-2,3,4-trihydroxy-butoxy)-5,6-dihydro-benzo[b]carbazol-11-one

[3681] ##STR00701##

[3682] Under the same conditions as the method for synthesizing Compound A7-14-2, the title compound was prepared from Compound T26-1 (17.0 mg, 90%).

[3683] LCMS: m/z 508 [M+H].sup.+

[3684] HPLC retention time: 1.77 min (analysis condition D)

Example 687

Compound T27-1

3-Bromo-9-(2-fluoro-4-methoxy-phenyl)-8-methoxy-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one

[3685] ##STR00702##

[3686] To the mixture of 6-bromo-7-methoxy-1,1-dimethyl-3,4-dihydro-1H-naphthalen-2-one (Compound E1, 410 mg, 1.44 mmol), tetrakistriphenylphosphine palladium (80 mg, 0.05 eq.) and sodium carbonate (614 mg, 4 eq.), toluene (3 mL) and water (1 ml) were added and then stirred at room temperature and at 90 C. for 3 hr. The mixture was extracted by adding water and diethyl ether, and the organic layer was washed with brine, and dried over magnesium sulfate. The residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain 6-(2-fluoro-4-methoxy-phenyl)-7-methoxy-1,1-dimethyl-3,4-dihydro-1H-naphthalen-2-one (white solid, 320 mg).

[3687] Thus-obtained 6-(2-fluoro-4-methoxy-phenyl)-7-methoxy-1,1-dimethyl-3,4-dihydro-1H-naphthalen-2-one (320 mg, 0.1 mmol) and 3-bromophenylhydrazine (0.29 g, 1.3 eq.) were dissolved in acetic acid (1 mL), and stirred under nitrogen atmosphere at 90 C. for 8 hr. After cooling, the reaction solution was added with ethyl acetate, washed with water, saturated aqueous solution of sodium hydrogen carbonate, and saturated brine, dried over magnesium sulfate, and then filtered. The residues obtained after concentration under reduced pressure were dissolved in THF (3 mL) comprising 10% water, added with DDQ (227 mg, 3 eq.) at room temperature, and stirred at room temperature for 2 hr. To the reaction solution, the mixture solution of THF/diethyl ether (1:1) was added, and the reaction solution was washed with 0.5 N aqueous solution of sodium hydroxide and saturated brine, dried over sodium sulfate, and then filtered. The residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain the title compound (red solid, 75 mg).

[3688] LCMS: m/z 494, 496 [M+H].sup.+

[3689] HPLC retention time: 3.10 min (analysis condition C)

Example 688

Compound T27-2

3-Bromo-9-(2-fluoro-4-hydroxy-phenyl)-8-hydroxy-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one

[3690] ##STR00703##

[3691] Under the same conditions as the method for synthesizing Compound A6, the title compound was prepared from Compound T27-1.

[3692] LCMS: m/z 464, 466 [M+H].sup.+

[3693] HPLC retention time: 2.68 min (analysis condition C)

Example 689

Compound U5

4-Bromo-8-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[3694] ##STR00704##

[3695] 2-Bromo-3-nitro-benzonitrile (Compound U1, 678 mg, 2.987 mmol) was dissolved in ethanol (20.9 mL) and water (8.96 mL), added with acetic acid (2.39 mL, 41.81 mmol) and iron (1.17 g, 20.91 mmol), and stirred at 60 C. for 18 hr. The reaction solution was poured into aqueous solution of sodium hydroxide (1 M), extracted with ethyl acetate, washed with water and saturated brine, dried over sodium sulfate, and then filtered. After concentration under reduced pressure, 3-amino-2-bromo-benzonitrile (Compound U2) was obtained as a crude product.

[3696] The crude product obtained from the above was dissolved in 12 M aqueous solution of hydrochloric acid (4.00 mL), added slowly at 0 C. with aqueous solution in which sodium nitrite (247 mg, 3.584 mmol) is dissolved in water (3.58 mL), and then the mixture was stirred at 0 C. for 30 min. Under light-shielding conditions, aqueous solution in which tin chloride dihydrate (2.02 g, 8.961 mmol) is dissolved in 12 M aqueous solution of hydrochloric acid (4.00 mL) was slowly added to the reaction solution at 0 C., and then the mixture was stirred at 0 C. for 1 hr. The reaction solution was poured into 5 M aqueous solution of sodium hydroxide, extracted with ethyl acetate, washed with saturated brine, dried over sodium sulfate, and filtered. After concentration under reduced pressure, 2-bromo-3-hydrazino-benzonitrile (Compound U3) was obtained as a crude product. Under nitrogen atmosphere, the above crude product and 7-methoxy-1,1-dimethyl-3,4-dihydro-1H-naphthalen-2-one (Compound A2, 462 mg, 2.260 mmol) were added with TFA (6.78 mL) and stirred at 100 C. for 2 hr. After cooling, the reaction solution was poured into saturated aqueous solution of sodium bicarbonate, extracted with ethyl acetate, washed with water and saturated brine, dried over sodium sulfate, and filtered. After concentration under reduced pressure, 4-bromo-8-methoxy-6,6-dimethyl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (Compound U4) was obtained as a crude product. The above crude product was dissolved in THF (10.0 mL) and water (1.00 mL), added with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (1.54 g, 6.780 mmol), and stirred at room temperature for 20 hr. The reaction solution was poured into 1 M aqueous solution of sodium hydroxide, extracted with cyclopentylmethyl ether, washed with 1 M aqueous solution of sodium hydroxide, water and saturated brine, dried over sodium sulfate, and filtered. The residues obtained after concentration under reduced pressure were washed with cyclopentylmethyl ether to obtain the title compound (460 mg, 52%).

[3697] LCMS: m/z 395 [M+H].sup.+

[3698] HPLC retention time: 2.25 min (analysis condition D)

Example 690

Compound U6

8-Hydroxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[3699] ##STR00705##

[3700] 4-Bromo-8-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (Compound U5, 325 mg, 0.822 mmol) was added with pyridine hydrochloride salt (3.80 g, 32.89 mmol) and stirred at 160 C. for 28 hr. The reaction solution was poured into water, extracted with ethyl acetate, washed with water, dried over sodium sulfate, and filtered. After concentration under reduced pressure, the title compound was obtained as a crude product.

[3701] LCMS: m/z 381 [M+H].sup.+

[3702] HPLC retention time: 1.92 min (analysis condition D)

Example 691

Compound U7-1

4-Bromo-8-((R)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[3703] ##STR00706##

[3704] Under the same conditions as the method for synthesizing Compound A7-1, the title compound was prepared from the reaction between Compound U6 and (R)-()-2,2-dimethyl-1,3-dioxolane-4-methanol (354 mg, 87%).

[3705] LCMS: m/z 495 [M+H].sup.+

[3706] HPLC retention time: 2.35 min (analysis condition D)

Example 692

Compound U7-2

4-Bromo-8-((S)-2,3-dihydroxy-propoxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[3707] ##STR00707##

[3708] Under the same conditions as the method for synthesizing Compound A7-14-2, the title compound was prepared from Compound U7-1.

[3709] LCMS: m/z 455 [M+H].sup.+

[3710] HPLC retention time: 2.40 min (analysis condition C)

Example 693

Compound U8-2

8-((R)-2,3-Dihydroxy-propoxy)-5,6,6-trimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[3711] ##STR00708##

[3712] Under the same conditions as the method for synthesizing Compound U7-1 and Compound U7-2, the title compound was prepared from the reaction between Compound U6 and (S)-(+)-2,2-dimethyl-1,3-dioxolane-4-methanol (4.5 mg, 29%).

[3713] LCMS: m/z 455 [M+H].sup.+

[3714] HPLC retention time: 2.37 min (analysis condition C)

Example 694

Compound U8-3-1

8-((S)-2,2-Dimethyl-[1,3]dioxolan-4-yl methoxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3,4-dicarbonitrile

[3715] ##STR00709##

[3716] Under nitrogen atmosphere, 4-bromo-8-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (Compound U6, 20.0 mg, 40.37 mol) was dissolved in DMA (0.35 mL), added with copper (I) cyanide (18.1 mg, 201.9 mol), and stirred at 200 C. for 1 hr under irradiation with microwave. The reaction solution was poured into water, extracted with ethyl acetate, washed with water and saturated brine, dried over sodium sulfate, and then filtered. The residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain the title compound as a crude product.

[3717] LCMS: m/z 442 [M+H].sup.+

[3718] HPLC retention time: 2.30 min (analysis condition D)

Example 695

Compound U8-3-2

8-((R)-2,3-Dihydroxy-propoxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3,4-dicarbonitrile

[3719] ##STR00710##

[3720] Under the same conditions as the method for synthesizing Compound A7-14-2, the title compound was prepared from Compound U8-3-1 (9.5 mg, 59%).

[3721] LCMS: m/z 402 [M+H].sup.+

[3722] HPLC retention time: 2.40 min (analysis condition D)

Example 696

Compound U8-4-1

8-((R)-2,2-Dimethyl-[1,3]dioxolan-4-yl methoxy)-4-hydroxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[3723] ##STR00711##

[3724] Under the same conditions as the method for synthesizing Compound U9, the title compound was prepared as a crude product from Compound U8-1 (9.5 mg, 59%).

[3725] LCMS: m/z 433 [M+H].sup.+

[3726] HPLC retention time: 2.34 min (analysis condition A)

Example 697

Compound U8-4-2

8-((R)-2,3-Dihydroxy-propoxy)-4-hydroxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[3727] ##STR00712##

[3728] Under the same conditions as the method for synthesizing Compound A7-14-2, the title compound was prepared from Compound U8-4-1 (crude product) (9.7 mg, 52%).

[3729] LCMS: m/z 393 [M+H].sup.+

[3730] HPLC retention time: 1.69 min (analysis condition A)

Example 698

Compound U8-4-3

8-((R)-2,3-Dihydroxy-propoxy)-4-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[3731] ##STR00713##

[3732] Under nitrogen atmosphere, 8-((R)-2,3-dihydroxy-propoxy)-4-hydroxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (Compound U8-4-2, 8.0 mg, 20.39 mol) was dissolved in methanol (2.0 mL) and chloroform (2.00 mL), added with trimethylsilyldiazomethane (diethyl ether solution, 2 M, 15.3 L, 30.58 mol) and diisopropylethylamine (0.05 mL), and then stirred at room temperature for 31 hr. The residues obtained from the reaction solution after concentration under reduced pressure were purified by silica gel column chromatography (methanol/dichloromethane) to obtain the title compound (5.1 mg, 62%).

[3733] LCMS: m/z 407 [M+H].sup.+

[3734] HPLC retention time: 3.74 min (analysis condition A)

Example 699

Compound U8-5-1

8-((R)-2,2-Dimethyl-[1,3]dioxolan-4-yl methoxy)-6,6-dimethyl-11-oxo-4-trifluoromethyl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[3735] ##STR00714##

[3736] Under nitrogen atmosphere, 4-bromo-8-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (Compound U8-1, 25.0 mg, 50.47 mol) was dissolved in DMF (0.75 mL), added with copper iodide (I) (48.0 mg, 252.3 mol) and difluoro-fluorosulfonyl-acetic acid methyl ester (31.9 L, 252.3 mol), and then stirred at 100 C. for 2 days. The reaction solution was poured into hydrochloric acid (1 M), extracted with ethyl acetate, washed with water, saturated aqueous solution of sodium bicarbonate and saturated brine, dried over sodium sulfate, and then filtered. The residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain the title compound as a crude product.

[3737] LCMS: m/z 485 [M+H].sup.+

[3738] HPLC retention time: 2.88 min (analysis condition A)

Example 700

Compound U8-5-2

8-((R)-2,3-Dihydroxy-propoxy)-6,6-dimethyl-11-oxo-4-trifluoromethyl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[3739] ##STR00715##

[3740] Under the same conditions as the method for synthesizing Compound A7-14-2, the title compound was prepared from Compound U8-5-1 (4.0 mg, 30%).

[3741] LCMS: m/z 445 [M+H].sup.+

[3742] HPLC retention time: 2.17 min (analysis condition A)

Example 701

Compound U8-6-1

4-Cyclopropyl-8-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[3743] ##STR00716##

[3744] Under nitrogen atmosphere, 2-cyclopropyl-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (13.2 mg, 78.73 mol) and potassium phosphate (212.27 mg, 212.0 mol) were dissolved in water (0.20 mL), and the mixture was stirred at room temperature for 15 min. To the reaction solution, 4-bromo-8-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (Compound U8-1, 30.0 mg, 60.56 mol), palladium acetate (1.36 mg, 6.056 mol), and tricyclohexylphosphine (toluene solution, 20 wt %, 17.0 mg, 12.11 mol) were added and the mixture was stirred at 80 C. for 24 hr. The reaction solution was poured into hydrochloric acid (1 M), extracted with ethyl acetate, washed with saturated aqueous solution of sodium bicarbonate and saturated brine, dried over sodium sulfate, and then filtered. The residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain the title compound (13.6 mg, 49%).

[3745] LCMS: m/z 457 [M+H].sup.+

[3746] HPLC retention time: 2.38 min (analysis condition D)

Example 702

Compound U8-6-2

4-Cyclopropyl-8-((R)-2,3-dihydroxy-propoxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[3747] ##STR00717##

[3748] Under the same conditions as the method for synthesizing Compound A7-14-2, the title compound was prepared from Compound U8-6-1.

[3749] LCMS: m/z 417 [M+H].sup.+

[3750] HPLC retention time: 2.42 min (analysis condition A)

Example 703

Compound U8-7-1

(S)-8-((2,2-Dimethyl-1,3-dioxolan-4-yl)methoxy)-4,6,6-trimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[3751] ##STR00718##

[3752] Under nitrogen atmosphere, 4-bromo-8-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (Compound U8-1, 30.0 mg, 60.56 mol) and lithium chloride (7.70 mg, 181.7 mol) were dissolved in DMF (1.00 mL), added with tetramethyl tin (12.5 L, 90.84 mol), tetrakistriphenylphosphine palladium (3.50 mg, 6.056 mol) and tricyclohexylphosphine (toluene solution, 20 wt %, 17.0 mg, 3.028 mol), and the mixture was stirred at 100 C. for 24 hr. The reaction solution was poured into hydrochloric acid (1 M), extracted with ethyl acetate, washed with water, saturated aqueous solution of sodium bicarbonate and saturated brine, dried over sodium sulfate, and then filtered. The residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain 8-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy)-4,6,6-trimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile as a crude product (20.9 mg, 80%).

Example 704

Compound U8-7-2

8-((R)-2,3-Dihydroxy-propoxy)-4,6,6-trimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[3753] ##STR00719##

[3754] Under the same conditions as the method for synthesizing Compound A7-14-2, the title compound was prepared from Compound U8-7-1.

[3755] LCMS: m/z 391 [M+H].sup.+

[3756] HPLC retention time: 1.82 min (analysis condition A)

Example 705

Compound U8-8-1

3-Cyano-8-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-4-carboxylic Acid Amide

[3757] ##STR00720##

[3758] Under nitrogen atmosphere, 4-bromo-8-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (Compound U8-1, 30.0 mg, 60.56 mol), palladium acetate (1.36 mg, 6.056 mol), 1,1-bis(diphenylphosphino)ferrocene (3.36 mg, 6.056 mol), imidazole (4.12 mg, 60.56 mol) and tert-potassium butoxy (10.2 mg, 90.84 mol) were dissolved in formamide (3.00 mL) and the mixture was stirred at 180 C. for 5 min under irradiation with microwave. The reaction solution was poured into water, extracted with ethyl acetate, washed with water and saturated brine, dried over sodium sulfate, and then filtered. The residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (methanol/dichloromethane) to obtain the target compound (7.6 mg, 27%).

[3759] LCMS: m/z 460 [M+H].sup.+

[3760] HPLC retention time: 1.82 min (analysis condition A)

Example 706

Compound U8-8-2

3-Cyano-8-((R)-2,3-dihydroxy-propoxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-4-carboxylic Acid

[3761] ##STR00721##

[3762] Under the same conditions as the method for synthesizing Compound A7-14-2, the title compound was prepared from Compound U8-8-1.

[3763] LCMS: m/z 421 [M+H].sup.+

[3764] HPLC retention time: 1.57 min (analysis condition A)

Example 707

Compound U8-8-3

3-Cyano-8-((R)-2,3-dihydroxy-propoxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-4-carboxylic Acid Amide

[3765] ##STR00722##

[3766] The title compound was obtained as a by-product of the synthesis of Compound U8-8-2.

[3767] LCMS: m/z 420 [M+H].sup.+

[3768] HPLC retention time: 1.27 min (analysis condition A)

Example 708

Compound U9

4-Hydroxy-8-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[3769] ##STR00723##

[3770] Under nitrogen atmosphere, 4-bromo-8-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (Compound U5, 10.0 mg, 25.30 mol), X-phos (1.07 mg, 2.530 mol), sodium hydroxide (4.36 mg, 75.90 mol) and Pd.sub.2dba.sub.3.CHCl.sub.3 (1.31 mg, 1.265 mol) were dissolved in dioxane (0.50 mL) and water (0.50 mL) and the mixture was stirred at 100 C. for 1 hr. The reaction solution was poured into hydrochloric acid (1 M), extracted with ethyl acetate, washed with saturated brine, dried over sodium sulfate, and then filtered. The residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane) and washed with dichloromethane to obtain the title compound (5.4 mg, 64%).

[3771] LCMS: m/z 333 [M+H].sup.+

[3772] HPLC retention time: 1.62 min (analysis condition D)

Example 709

Compound U10-1

4-((R)-2,3-Dihydroxy-propoxy)-8-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[3773] ##STR00724##

[3774] Under the same conditions as the method for synthesizing Compound A7-1, the title compound was prepared from the reaction between Compound U9 and (S)-(+)-2,2-dimethyl-1,3-dioxolane-4-methanol.

[3775] LCMS: m/z 407 [M+H].sup.+

[3776] HPLC retention time: 2.06 min (analysis condition A)

Example 710

Compound U10-2

4-((S)-2,3-Dihydroxy-propoxy)-8-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[3777] ##STR00725##

[3778] Under the same conditions as the method for synthesizing Compound A7-1, the title compound was prepared from the reaction between Compound U9 and (R)-()-2,2-dimethyl-1,3-dioxolane-4-methanol.

[3779] LCMS: m/z 407 [M+H].sup.+

[3780] HPLC retention time: 2.06 min (analysis condition A)

Example 711

Compound U11

4-Amino-8-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[3781] ##STR00726##

[3782] Under nitrogen atmosphere, 4-bromo-8-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (Compound U5, 25.0 mg, 63.25 mol), copper iodide (2.41 mg, 12.65 mol), sodium azide (20.6 mg, 316.3 mol), (1S,2S)N,N-dimethyl-cyclohexane-1,2-diamine (2.70 mg, 18.98 mol), and sodium ascorbate (1.25 mg, 6.325 mol) were dissolved in ethanol (0.70 mL) and water (0.30 mL) and the mixture was stirred at 100 C. for 2 hr. The reaction solution was poured into aqueous solution of sodium hydroxide (1 M), extracted with ethyl acetate, washed with water and saturated brine, dried over sodium sulfate, and then filtered. The residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (methanol/dichloromethane) to obtain the title compound (5.6 mg, 27%).

[3783] LCMS: m/z 332 [M+H].sup.+

[3784] HPLC retention time: 2.16 min (analysis condition A)

Example 712

Compound V2

3-Fluoro-8-methoxy-6,6-dimethyl-6,11-dihydro-5H-benzo[b]carbazole

[3785] ##STR00727##

[3786] Under nitrogen atmosphere, the acetic acid (1 mL) suspension of 7-methoxy-1,1-dimethyl-3,4-dihydro-1H-naphthalen-2-one (Compound A2, 101.0 mg, 0.495 mmol) and (3-fluoro-phenyl)-hydrazine hydrochloric acid salt (Compound VI, 96.5 mg, 0.593 mmol) was stirred at ambient temperature of 95 C. for 3.75 hr. After cooling to room temperature, the reaction mixture was added with water (1 mL) and hexane/ethyl acetate (15:1) (0.5 mL), and stirred at room temperature for 15 min. The solid was filtered, washed with hexane/ethyl acetate (15:1), and then dried under reduced pressure to obtain the title compound (beige powder, 72.7 mg, 50%).

[3787] .sup.1H-NMR (270 MHz, CDCl.sub.3) : 7.92-7.82 (1H, b), 7.47 (1H, dd, 8.9 Hz, 5.6 Hz), 7.10-7.03 (2H, m), 6.95-6.81 (2H, m), 4.05 (2H, s), 3.86 (3H, s), 1.67 (6H, s)

Example 713

Compound V3

3-Fluoro-8-methoxy-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one

[3788] ##STR00728##

[3789] Under nitrogen atmosphere, to the THF (1.8 mL)-water (0.18 mL) solution of 3-fluoro-8-methoxy-6,6-dimethyl-6,11-dihydro-5H-benzo[b]carbazole (Compound V2, 72.4 mg, 0.245 mmol), DDQ (122.4 mg, 0.539 mmol) was added and the mixture was stirred at room temperature for 5 hr. The reaction mixture was added with diethyl ether and 0.5 N aqueous solution of sodium hydroxide (2 mL), and the resulting mixture was extracted twice with diethyl ether. The organic layer was washed twice with 0.5 N aqueous solution of sodium hydroxide (2 mL) and subsequently twice with brine (2 mL), and dried over sodium sulfate. After concentration under reduced pressure, hexane/ethyl acetate (5:1) and diethyl ether were added to the obtained crude product, and the solid was triturated. After removing the supernatant and drying under reduced pressure, the title compound was obtained (yellow solid, 57.0 mg, 75%).

[3790] .sup.1H-NMR (270 MHz, CDCl.sub.3) : 8.54-8.44 (1H, b), 8.43-8.33 (2H, m), 7.16-6.98 (4H, m), 3.93 (3H, s), 1.77 (6H, s)

Example 714

Compound V4

3-Fluoro-8-hydroxy-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one

[3791] ##STR00729##

[3792] Mixture of 3-fluoro-8-methoxy-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one (Compound V3, 56.6 mg, 0.183 mmol) and pyridinium chloride (0.65 g) was stirred at ambient temperature of 160 C. for 12 hr. The reaction mixture was cooled to room temperature, added with ethyl acetate and water, and the resulting mixture was extracted four times with ethyl acetate. The organic layer was washed with water three times, dried over sodium sulfate, and concentrated under reduced pressure. The obtained crude product was used for the next step without further purification (brown solid, 61.6 mg, 100%).

[3793] .sup.1H-NMR (270 MHz, CD.sub.3OD) : 8.20 (1H, dd, 8.9 Hz, 5.3 Hz), 8.15 (1H, d, 9.6 Hz), 7.17 (1H, dd, 9.6 Hz, 2.3 Hz), 7.12 (1H, d, 2.3 Hz), 7.05-6.95 (1H, m), 6.88 (1H, dd, 8.9 Hz, 2.3 Hz), 1.74 (6H, s)

Example 715

Compound V5-1

8-[(1R,5R)-5-(Tert-butyl-dimethyl-silanyloxymethyl)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy]-3-fluoro-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one

[3794] ##STR00730##

[3795] Under nitrogen atmosphere, to the THF (1.5 mL) solution of 3-fluoro-8-hydroxy-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one (Compound V4, 0.183 mmol), (4S,5R)-5-(tert-butyl-dimethyl-silanyloxymethyl)-2,2-dimethyl[1,3]dioxolan-4-ol (75.9 mg, 0.275 mmol) and triphenylphosphine (72 mg, 0.275 mmol), toluene solution (125 L, 0.275 mmol) of DEAD was added dropwise at room temperature. The reaction mixture was stirred at ambient temperature of 40 C. for 7 hr. After cooling to room temperature, the reaction mixture was concentrated under reduced pressure, and the resulting crude product was purified by preparative TLC (Merck 60 F254, 0.5 mm) {solution for elution: hexane/ethyl acetate (3:1)} to obtain the title compound (pale orange amorphous, 54.1 mg, 53.4%).

[3796] .sup.1H-NMR (270 MHz, CDCl.sub.3) : 8.54-8.45 (1H, b), 8.42-8.33 (2H, m), 7.17-6.99 (4H, m), 4.41-4.27 (2H, m), 4.25-4.15 (1H, m), 4.06-3.96 (1H, m), 3.96-3.88 (1H, m), 3.83-3.74 (1H, m), 1.76 (3H, s), 1.75 (3H, s), 1.48 (3H, s), 1.47 (3H, s), 0.87 (9H, s), 0.092 (6H, s)

Example 716

Compound V5-2

3-Fluoro-6,6-dimethyl-8-((3R,4R)-2,3,4-trihydroxy-butoxy)-5,6-dihydro-benzo[b]carbazol-11-one

[3797] ##STR00731##

[3798] Under nitrogen atmosphere, to the THF (0.3 mL)-MeOH (0.1 mL) solution of 8-[(1R,5R)-5-(tert-butyl-dimethyl-silanyloxymethyl)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy]-3-fluoro-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one (Compound V5-1, 52.8 mg, 0.0954 mmol), 0.5 M aqueous solution of sulfuric acid (0.19 mL, 0.0954 mmol) was added at room temperature. The reaction mixture was stirred at ambient temperature of 55 C. for 4 hr, cooled to room temperature, and then added with diethyl ether, sodium hydrogen carbonate (20 mg) and water in order. The mixture was extracted twice with diethyl ether and subsequently twice with ethyl acetate, and the organic layer was washed with brine, dried over sodium sulfate, and concentrated under reduced pressure. The resulting crude product was washed with dichloromethane, and dried under reduced pressure to obtain the title compound (white powder, 29.9 mg, 78%).

[3799] .sup.1H-NMR (270 MHz, CD.sub.3OD) : 8.24 (1H, d, 8.9 Hz), 8.19 (1H, dd, 8.6 Hz, 5.3 Hz), 7.30 (1H, d, 2.3 Hz), 7.18 (1H, dd, 9.2 Hz, 2.3 Hz), 7.09 (1H, dd, 8.9 Hz, 2.3 Hz), 7.06-6.96 (1H, m), 4.32-4.22 (1H, m), 4.21-4.12 (1H, m), 4.11-4.02 (1H, m), 3.84-3.75 (1H, m), 3.74-3.61 (2H, m), 1.77 (6H, s)

[3800] LCMS: m/z 400 [M+H].sup.+

[3801] HPLC retention time: 4.02 min (analysis condition H)

Example 717

Compound W2

7-((S)-2,3-Dihydroxy-propoxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[3802] ##STR00732##

[3803] To the toluene suspension of sodium t-butoxide (700 mg, 2.5 eq.), 8-methoxy-3,4-dihydro-1H-naphthalen-2-one (Compound W1, 500 mg, 2.9 mmol) was added dropwise at 0 C. After 15 minutes, the solution turned into blackish green color. The mixture solution was added dropwise with methyl iodide (1.03 g, 2.5 eq.) and stirred at 15 C. overnight. Brown solid precipitated. The reaction solution was added to saturated aqueous solution of ammonium chloride/diethyl ether under stirring and cooling. After that, the solution was extracted with diethyl ether, and dried over sodium sulfate. After removing the solvent under reduced pressure, the resulting residues were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain 8-methoxy-1,1-dimethyl-3,4-dihydro-1H-naphthalen-2-one (350 mg).

[3804] Thus-obtained 8-methoxy-1,1-dimethyl-3,4-dihydro-1H-naphthalen-2-one (250 mg, 1.23 mmol) and 3-cyanophenylhydrazine (0.2 g, 1.2 eq.) were dissolved in trifluoroacetic acid (1 mL), and stirred at 120 C. for 1 hr under irradiation with microwave. After cooling, the reaction solution was added with ethyl acetate, washed with water, saturated aqueous solution of sodium hydrogen carbonate, and saturated brine, dried over magnesium sulfate, and filtered. The residues obtained after concentration under reduced pressure were dissolved in THF (3 mL) comprising 10% water and added at room temperature with DDQ (227 mg, 3 eq.). The mixture was then stirred at room temperature for 2 hr. The reaction solution was added with mixture solution of THF/diethyl ether (1:1), washed with 0.5 N aqueous solution of sodium hydroxide and saturated brine, dried over sodium sulfate, and then filtered. The residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain 7-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (brown solid, 54 mg).

[3805] LCMS: m/z 317 [M+H].sup.+

[3806] HPLC retention time: 1.00 min (analysis condition I)

Example 718

Compound W3

7-Hydroxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[3807] ##STR00733##

[3808] Under the same conditions as Compound A6, the title compound was prepared from Compound W2.

[3809] LCMS: m/z 316 [M+H].sup.+

[3810] HPLC retention time: 0.93 min (analysis condition I)

Example 719

Compound W4-1

7-((R)-2,2-Dimethyl-[1,3]dioxolan-4-yl methoxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[3811] ##STR00734##

[3812] Under nitrogen atmosphere, 7-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (Compound W3, 15 mg, 0.05 mmol) and triphenylphosphine (40 mg, 3 eq.) were added with THF (1 ml), further added dropwise with ((R)-2,2-dimethyl-[1,3]dioxolan-4-yl)-methanol (20 mg, 3 eq.) and 2.19 N toluene solution of diethyl azodicarboxylate (68 L, 3 eq.), and the mixture was stirred at 50 C. for 2 hr. After cooling, the reaction solution was added with ethyl acetate, washed with brine, dried over sodium sulfate, and filtered. The residues obtained after concentration under reduced pressure were purified by preparative TLC (ethyl acetate/dichloromethane), and the resulting solid was washed with dichloromethane to obtain the target compound (brown powder, 5 mg).

[3813] LCMS: m/z 417 [M+H].sup.+

[3814] HPLC retention time: 1.04 min (analysis condition I)

Example 720

Compound W4-2

7-((S)-2,3-Dihydroxy-propoxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[3815] ##STR00735##

[3816] Under the same conditions as Compound S7-2, the title compound was prepared from Compound W4-1.

[3817] LCMS: m/z 377 [M+H].sup.+

[3818] HPLC retention time: 0.88 min (analysis condition I)

Example 721

Compound X1

1,1-Spiro-4-piperidine-N-paratoluenesulfonyl-7-methoxy-3,4-dihydro-1H-naphthalen-2-one

[3819] ##STR00736##

[3820] 7-Methoxy-3,4-dihydro-1H-naphthalen-2-one (Compound A1, 100 mg, 0.568 mmol) was dissolved in toluene (4 mL), added with NaH (60% in oil, 68 mg, 3 eq.), and stirred at room temperature for 10 min. The mixture solution was added with bis-(2-iodo-ethyl)-p-toluenesulfonamide (172 mg, 0.568 mmol), and stirred at 70 C. for 2 hr under nitrogen stream. After cooling, the reaction solution was added to saturated aqueous solution of ammonium chloride, extracted with ethyl acetate, washed with saturated brine, and then dried over magnesium sulfate. The residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (hexane:ethyl acetate/3:1) to obtain the title compound (colorless oily substance, 62 mg, 33%).

[3821] LCMS: m/z 400 [M+H].sup.+

[3822] HPLC retention time: 2.02 min (analysis condition B)

Example 722

Compound X2

1,1-Spiro-4-piperidine-N-paratoluenesulfonyl-7-methoxy-3,4-dihydro-1H-naphthalen-2-one

[3823] ##STR00737##

[3824] 1,1-Spiro-4-piperidine-N-paratoluenesulfonyl-7-methoxy-3,4-dihydro-1H-naphthalen-2-one (Compound X1, 400 mg, 1.0 mmol) and phenylhydrazine (217 mg, 1.5 eq.) were dissolved in acetic acid (6 mL), and the mixture was stirred at 120 C. for 4 hr under nitrogen atmosphere. After cooling, the reaction solution was added to water, extracted with ethyl acetate, washed with saturated brine, and then dried over magnesium sulfate. The residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (hexane:ethyl acetate/4:1) to obtain the title compound (brown solid, 185 mg, 43%).

[3825] LCMS: m/z 473 [M+H].sup.+

[3826] HPLC retention time: 7.23 min (analysis condition B)

Example 723

Compound X3

6,6-Spiro-4-piperidine-N-paratoluenesulfonyl-8-methoxy-5,6-dihydro-benzo[b]carbazol-11-one

[3827] ##STR00738##

[3828] 6,6-Spiro-4-piperidine-N-paratoluenesulfonyl-8-methoxy-5,6-dihydro-5H-benzo[b]carbazole (Compound X2, 400 mg, 0.848 mmol) and DDQ (770 mg, 4 eq.) were dissolved in THF (10 mL) and water (2 mL), and then the mixture was stirred at 50 C. for 5 hr. After cooling, the reaction solution was added to saturated aqueous solution of sodium hydrogen carbonate, extracted with ethyl acetate, washed with saturated brine, and then dried over magnesium sulfate. The residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (hexane:ethyl acetate/3:1) to give a solid, which was then washed with ethyl ether to obtain the title compound (yellow solid, 86 mg, 21%).

[3829] .sup.1H-NMR (400 MHz, DMSO-d.sub.6) : 11.9 (1H, s), 8.22 (2H, m), 7.75 (2H, d), 7.60 (4H, m) 7.30 (2H, m), 7.11 (1H, d), 3.81 (2H, m), 3.68 (3H, s), 3.62 (2H, m), 2.49 (3H, s), 2.21 (2H, m), 2.10 (2H, m),

[3830] LCMS: m/z 487 [M+H].sup.+

[3831] HPLC retention time: 6.05 min (analysis condition B)

Example 724

Compound X4

6,6-Spiro-4-piperidine-8-hydroxy-5,6-dihydro-benzo[b]carbazol-11-one

[3832] ##STR00739##

[3833] Mixture of 6,6-spiro-4-piperidine-N-paratoluenesulfonyl-8-methoxy-5,6-dihydro-benzo[b]carbazol-11-one (Compound X3, 35 mg, 0.072 mmol) and pyridine hydrochloride salt (800 mg) was stirred in a sealing tube at 160 C. for 10 hr. After cooling, the reaction solution was added to water, extracted with ethyl acetate, washed with saturated brine, and then dried over magnesium sulfate. The residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (dichloromethane:methanol/4:1) to obtain the title compound (yellow solid, 30 mg, 98%).

[3834] .sup.1H-NMR (400 MHz, DMSO-d.sub.6) : 8.20 (1H, m), 8.10 (1H, m), 7.53 (1H, m), 7.25 (3H, m), 6.80 (1H, m), 3.60 (2H, m), 3.45 (2H, m), 2.52 (2H, m), 2.05 (2H, m).

[3835] LCMS: m/z 319 [M+H].sup.+

[3836] HPLC retention time: 2.86 min (analysis condition B)

Example 725

Compound X5

8-(2-Diethylaminoethoxy)-6,6-spiro-4-piperidine-8-hydroxy-5,6-dihydro-benzo[b]carbazol-11-one

[3837] ##STR00740##

[3838] 6,6-Spiro-4-piperidine-8-hydroxy-5,6-dihydro-benzo[b]carbazol-11-one (Compound X4, 30 mg, 0.094 mmol), diethylaminoethanol (22 mg, 2 eq.), triphenylphosphine (50 mg, 2 eq.) and DIAD (39 mg, 2 eq.) were dissolved in THF (4 mL) and the mixture was stirred at room temperature for 4 hr. The reaction solution was added to water, extracted with ethyl acetate, washed with saturated brine, and then dried over magnesium sulfate. The residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (dichloromethane:methanol/4:1) to obtain the title compound (yellow oily substance, 6.8 mg, 17%).

[3839] LCMS: m/z 418 [M+H].sup.+

[3840] HPLC retention time: 2.75 min (analysis condition B)

Example 726

Compound Y2

2,3-Dichloro-8-methoxy-6,6-dimethyl-6,11-dihydro-5H-benzo[b]carbazole

[3841] ##STR00741##

[3842] Under nitrogen atmosphere, the acetic acid (1 mL) suspension of 7-methoxy-1,1-dimethyl-3,4-dihydro-1H-naphthalen-2-one (Compound A2, 92.3 mg, 0.452 mmol) and (3,4-dichlorophenyl)hydrazine hydrochloric acid salt (Compound Y1, 96.5 mg, 0.452 mmol) was stirred at ambient temperature of 90 C. for 3.5 hr. After cooling to room temperature, the reaction mixture was added with diethyl ether and water, and the resulting mixture was extracted twice with diethyl ether. The organic layer was washed three times with water, dried over sodium sulfate, and concentrated under reduced pressure. The resulting crude product was purified by flash column chromatography {Merck Kieselgel60, solution for elution: hexane/ethyl acetate (4:1)} to obtain the title compound (pale yellow solid, 62.1 mg, 40%).

[3843] .sup.1H-NMR (270 MHz, CDCl.sub.3) : 7.92-7.84 (1H, b), 7.62 (1H, s), 7.46 (1H, s), 7.05 (1H, d, 2.6), 6.84 (1H, dd, 8.6 Hz, 2.6 Hz), 4.01 (2H, s), 3.86 (3H, s), 1.67 (6H, s)

Example 727

Compound Y3

2,3-Dichloro-8-methoxy-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one

[3844] ##STR00742##

[3845] Under nitrogen atmosphere, to the 1,4-dioxane (1.7 mL)-water (0.1 mL) solution of 2,3-dichloro-8-methoxy-6,6-dimethyl-6,11-dihydro-5H-benzo[b]carbazole (Compound Y2, 61.0 mg, 0.176 mmol), DDQ (120 mg, 0.529 mmol) was added and the mixture was stirred at room temperature for 16 hr and 15 min. The reaction mixture was purified by flash column chromatography {Merck Kieselgel60, solution for elution: hexane/ethyl acetate (2:1)} to obtain the title compound (pale orange solid, 16.7 mg, 26%).

[3846] .sup.1H-NMR (270 MHz, CDCl.sub.3) : 8.55 (1H, s), 8.42-8.36 (1H, b), 8.39 (1H, d, 8.6 Hz), 7.54 (1H, s), 7.08 (1H, d, 2.3 Hz), 7.03 (1H, dd, 8.6 Hz, 2.3 Hz), 3.93 (3H, s), 1.76 (6H, s)

Example 728

Compound Y4

2,3-Dichloro-8-hydroxy-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one

[3847] ##STR00743##

[3848] Mixture of 2,3-dichloro-8-methoxy-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one (Compound Y3, 16.5 mg, 0.0457 mmol) and pyridinium chloride (0.2 g) was stirred at ambient temperature of 160 C. for 7 hr. The reaction mixture was cooled to room temperature and added with ethyl acetate and water. The mixture was extracted three times with ethyl acetate. The organic layer was washed twice with water, dried over sodium sulfate, and concentrated under reduced pressure. The resulting crude product was used for the next step without further purification (brown solid, 14.8 mg, 94%).

[3849] .sup.1H-NMR (270 MHz, CD.sub.3OD) : 8.34 (1H, s), 8.14 (1H, d, 8.6 Hz), 7.61 (1H, s), 7.10 (1H, d, 2.3 Hz), 6.89 (1H, dd, 8.6 Hz, 2.3 Hz), 1.75 (1H, s)

Example 729

Compound Y5-1

8-[(1R,5R)-5-(Tert-butyldimethylsilanyloxymethyl)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy]-2,3-dichloro-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one

[3850] ##STR00744##

[3851] Under nitrogen atmosphere, to the THF (0.3 mL) solution of 2,3-dichloro-8-hydroxy-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one (Compound Y4, 12.9 mg, 0.0373 mmol), (4S,5R)-5-(tert-butyldimethylsilanyloxymethyl)-2,2-dimethyl-[1,3]dioxolan-4-ol (15.5 mg, 0.0559 mmol) and triphenylphosphine (14.7 mg, 0.0559 mmol), toluene solution (25.4 L, 0.0559 mmol) of DEAD was added dropwise at room temperature. The reaction mixture was stirred at ambient temperature of 40 C. for 4 hr. After cooling to room temperature, the reaction mixture was concentrated under reduced pressure, and the resulting crude product was purified by preparative TLC (Merck 60 F254, 0.5 mm) {solution for elution: hexane/ethyl acetate (3:1)} to obtain the title compound (white solid, 15.1 mg, 67%).

[3852] .sup.1H-NMR (270 MHz, CDCl.sub.3) : 8.55 (1H, s), 8.44-8.37 (1H, b), 8.37 (1H, d, 8.6 Hz), 7.54 (1H, s), 7.15 (1H, d, 2.6 Hz), 7.03 (1H, dd, 8.6 Hz, 2.6 Hz), 4.41-4.26 (2H, m), 4.25-4.15 (1H, m), 4.06-3.86 (2H, m), 3.83-3.73 (1H, m), 1.76 (3H, s), 1.75 (3H, s), 1.48 (3H, s), 1.47 (3H, s), 0.90 (9H, s), 0.092 (6H, s)

Example 730

Compound Y5-2

2,3-Dichloro-6,6-dimethyl-8-((3R,4R)-2,3,4-trihydroxy-butoxy)-5,6-dihydro-benzo[b]carbazol-11-one

[3853] ##STR00745##

[3854] Under nitrogen atmosphere, to the THF (0.2 mL)-MeOH (0.1 mL) solution of 8-[(1R,5R)-5-(tert-butyldimethyl-silanyloxymethyl)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy]-2,3-dichloro-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one (Compound Y5-1, 14.6 mg, 0.0242 mmol), 0.5 M aqueous solution of sulfuric acid (96.6 L, 0.0483 mmol) was added at room temperature. The reaction mixture was stirred at ambient temperature of 55 C. for 3 hr, cooled to room temperature, and then added with diethyl ether and sodium hydrogen carbonate (10 mg) in order. The mixture was extracted twice with diethyl ether, and the organic layer was washed with water and brine, dried over sodium sulfate, and concentrated under reduced pressure. The resulting crude product was washed with dichloromethane, and dried under reduced pressure to obtain the title compound (white solid, 8.3 mg, 76%).

[3855] .sup.1H-NMR (270 MHz, CD.sub.3OD) : 8.35 (1H, s), 8.24 (1H, d, 8.9 Hz), 7.62 (1H, s), 7.31 (1H, d, 2.3 Hz), 7.10 (1H, dd, 8.9 Hz, 2.3 Hz), 4.31-4.23 (1H, m), 4.12-4.12 (1H, m), 4.11-4.02 (1H, m), 3.84-3.74 (1H, m), 3.73-3.61 (1H, m), 1.78 (6H, s)

[3856] LCMS: m/z 450 [M+H].sup.+

[3857] HPLC retention time: 4.92 min (analysis condition H)

Example 731

Compound Z3

2-[1-(2-Bromo-5-methoxy-phenyl)-1-methylethyl]-benzo[b]thiophene

[3858] ##STR00746##

[3859] 2-(2-Bromo-5-methoxyphenyl)-2-methyl-propionic acid (1.5 g, 5.5 mmol) was dissolved in methylene chloride (15 mL), added with oxalyl chloride (1.5 mL) and dimethylformamide (2 micro liter) at room temperature, and the mixture was stirred at room temperature for 30 min. After removing the solvent, the residues were dissolved in toluene, added at room temperature with 2-[(triphenyl-5-phosphanyl)-methyl]-benzenethiol hydrobromide (2.56 g, 5.5 mmol) and triethylamine (2.27 mL), and then the mixture was refluxed under heating for 30 min. Thereafter, the mixture was cooled to 0 C., added with lithium hexamethyldisilazide (1 M tetrahydrofuran solution, 5.5 mL), and refluxed under heating for 24 hr. The reaction mixture was extracted with ethyl acetate and washed with water. The organic layer was dried over magnesium sulfate. The residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain the title compound (0.55 g, 28%).

[3860] .sup.1H-NMR (270 MHz, CDCl.sub.3) : 6.61 (1H, s), 3.37 (3H, s), 1.83 (6H, s)

Example 732

Compound Z4

2-(1-Benzo[b]thiophen-2-yl-1-methyl-ethyl)-4-methoxy-benzoic Acid

[3861] ##STR00747##

[3862] 2-[1-(2-Bromo-5-methoxy-phenyl)-1-methylethyl]-benzo[b]thiophene (Compound Z3, 40 mg, 0.11 mmol) was dissolved in tetrahydrofuran (0.5 mL), cooled to 78 C., added with n-butyl lithium (1.57 M, hexane solution, 0.07 mL), and the mixture was stirred for 10 min. The reaction mixture was added with dry ice and then maintained for 1 hr. After that, the mixture was added with 0.5 N hydrochloric acid, extracted with ethyl acetate and washed with water. The organic layer was dried over magnesium sulfate. The residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain the title compound (22 mg, 55%).

[3863] .sup.1H-NMR (270 MHz, CDCl.sub.3) : 7.46 (1H, d), 7.44 (1H, d), 6.92 (s, 1H), 6.70 (d, 1H), 3.84 (s, 3H), 1.89 (6H, s)

Example 733

Compound Z5

8-Methoxy-6,6-dimethyl-6H-benzo[b]naphth[2,3-d]thiophen-11-one

[3864] ##STR00748##

[3865] To 2-(1-benzo[b]thiophen-2-yl-1-methylethyl)-4-methoxy-benzoic acid (Compound Z4, 68 mg, 0.22 mmol), polyphosphoric acid (3.5 g) was added, and the mixture was stirred for 1 hr at 100 C. under heating. The mixture was added with water, extracted with ethyl acetate and washed with water. The organic layer was dried over magnesium sulfate. The residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain the title compound (41 mg, 63%).

[3866] LCMS: m/z 309 [M+H].sup.+

[3867] HPLC retention time: 2.89 min (analysis condition C)

Example 734

Compound Z6

8-Hydroxy-6,6-dimethyl-6H-benzo[b]naphth[2,3-d]thiophen-11-one

[3868] ##STR00749##

[3869] Under the same conditions as Compound A6, the title compound was prepared from Compound Z5.

[3870] LCMS: m/z 295 [M+H].sup.+

[3871] HPLC retention time: 2.91 min (analysis condition F)

Example 735

Compound Z7

8-(2-Diethylamino-ethoxy)-6,6-dimethyl-6H-benzo[b]naphth[2,3-d]thiophen-11-one

[3872] ##STR00750##

[3873] According to the same method as the method for synthesizing Compound A7-17, the title compound was prepared from Compound Z6.

[3874] LCMS: m/z 394 [M+H].sup.+

[3875] HPLC retention time: 5.06 min (analysis condition F)

Example 736

Compound Z9

2-Bromo-1,3-dihydroxytetrahydropyranbenzene

[3876] ##STR00751##

[3877] To 4-bromo-benzene-1,3-diol (Compound Z8, 20 g, 105.8 mmol) and 3,4-dihydro-2H-pyran (38.6 mL), pyridium paratoluenesulfonate (266 mg) was added, and the mixture was stirred at 50 C. for 1 hr. The residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain the title compound (31.82 mg, 84%).

[3878] LCMS: m/z 358 [M+H].sup.+

[3879] HPLC retention time: 3.15 min (analysis condition C)

Example 737

Compound Z10

3-(2,4-Dihydroxy-phenyl)-7-methoxy-1,1-dimethyl-3,4-dihydro-1H-naphthalen-2-one

[3880] ##STR00752##

[3881] To 7-methoxy-1,1-dimethyl-3,4-dihydro-1H-naphthalen-2-one (Compound A2, 10 g), 2-bromo-1,3-dihydroxytetrahydropyranbenzene (Compound Z9, 20.98 g), sodium t-butoxide (5.88 g), palladium acetate (550 mg) and tri-t-butylphosphonium tetrafluoroborate (710 mg), toluene (40 mL) was added and the mixture was stirred and heated at 70 C. under nitrogen atmosphere for 6 hr. After cooling, the reaction mixture was added with methanol (38 mL) and trifluoroacetic acid (14.54 mL) at room temperature, and then stirred at room temperature overnight. To the resulting residues, methylene chloride and saturated dipotassium hydrogen phosphate were added and the organic layer was washed with saturated brine. Thereafter, the organic layer was dried over magnesium sulfate. The residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain the title compound (5.53 g, 36%).

[3882] LCMS: m/z 312 [M+H].sup.+

[3883] HPLC retention time: 2.39 min (analysis condition F)

Example 738

Compound Z11

Trifluoromethanesulfonic Acid 8-methoxy-6,6-dimethyl-6,11-dihydro-benzo[b]naphth[2,3-d]furan-3-yl Ester

[3884] ##STR00753##

[3885] 3-(2,4-Dihydroxy-phenyl)-7-methoxy-1,1-dimethyl-3,4-dihydro-1H-naphthalen-2-one (Compound Z10, 5.53 g) was dissolved in methylene chloride (40 mL), and added with trifluoromethanesulfonic anhydride (2.98 mL) at room temperature. After cooling to 5 C., diisopropylethylamine (9.25 mL) and trifluoromethanesulfonic anhydride (4.47 mL) were added thereto. To the reaction mixture, methylene chloride and saturated dipotassium hydrogen phosphate were added and the organic layer was washed with saturated brine. Thereafter, the organic layer was dried over magnesium sulfate. The residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain the title compound (4.82 g, 64%).

[3886] LCMS: m/z 427 [M+H].sup.+

[3887] HPLC retention time: 8.95 min (analysis condition H)

Example 739

Compound Z12

Trifluoromethanesulfonic Acid 8-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-benzo[b]naphth[2,3-d]furan-3-yl Ester

[3888] ##STR00754##

[3889] Trifluoromethanesulfonic Acid 8-methoxy-6,6-dimethyl-6,11-dihydro-benzo[b]naphth[2,3-d]furan-3-yl ester (Compound Z11, 4.82 g) was dissolved in acetonitrile (48 mL) and water (24 mL), added with sodium chlorite (2.55 g) and N hydroxyphthalimide (369 mg), and then the mixture was stirred at 40 C. for 1 hr. The reaction mixture was added with methylene chloride and the organic layer was washed with saturated brine. Thereafter, the organic layer was dried over magnesium sulfate. The residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain the title compound (2.80 g, 56%).

[3890] LCMS: m/z 441 [M+H].sup.+

[3891] HPLC retention time: 8.02 min (analysis condition H)

Example 740

Compound Z13

Trifluoromethanesulfonic Acid 8-hydroxy-6,6-dimethyl-11-oxo-6,11-dihydro-benzo[b]naphth[2,3-d]furan-3-yl Ester

[3892] ##STR00755##

[3893] Under the same conditions as Compound A6, the title compound was prepared as a crude product from Compound Z12.

Example 741

Compound Z14

Trifluoro-methanesulfonic Acid 8-[(4R,5R)-5-(tert-butyl-dimethyl-silanyloxymethyl)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy]-6,6 dimethyl-11-oxo-6,11-dihydro-benzo[b]naphth[2,3-d]furan-3-yl Ester

[3894] ##STR00756##

[3895] Under the same conditions as the method for synthesizing Compound A7-1, the title compound was obtained as a crude product from Compound Z13 and [5-(tert-butyldimethylsilanyloxymethyl)-2,2-dimethyl-[1,3]dioxolan-4-yl]-methanol (Compound T22-0).

Example 742

Compound Z15

8-[(4R,5R)-5-(Tert-butyl-dimethyl-silanyloxymethyl)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy]-6,6-dimethyl-11-oxo-6,11-dihydro-benzo[b]naphth[2,3-d] furane-3-carbonitrile

[3896] ##STR00757##

[3897] Trifluoro-methanesulfonic Acid 8-[(4R,5R)-5-(tert-butyl-dimethyl-silanyloxymethyl)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy]-6,6 dimethyl-11-oxo-6,11-dihydro-benzo[b]naphth[2,3-d]furan-3-yl ester (Compound Z14, 24 mg) was dissolved in DMF (0.5 mL), added with zinc (II) cyanide (8.2 mg) and palladium tetrakistriphenylphosphine (2.0 mg), and the mixture was stirred under heating at 200 C. for 20 min with microwave irradiation. To the reaction mixture, ethyl acetate was added and the organic layer was washed with saturated brine. Thereafter, the organic layer was dried over magnesium sulfate. The residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain the title compound (15 mg).

[3898] LCMS: m/z 562 [M+H].sup.+

[3899] HPLC retention time: 4.14 min (analysis condition F)

Example 743

Compound Z16

6,6-Dimethyl-11-oxo-8-((2R,3R)-2,3,4-trihydroxy-butoxy)-6,11-dihydro-benzo[b]naphth[2,3-d]furane-3-carbonitrile

[3900] ##STR00758##

[3901] Under the same conditions as Compound S7-2, the title compound was prepared from Compound Z15.

[3902] LCMS: m/z 408 [M+H].sup.+

[3903] HPLC retention time: 4.51 min (analysis condition H)

Example 744

Compound K7-5

4-(3-Cyano-9-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl)-3,6-dihydro-2H-pyridine-1-carboxylic Acid Tert-Butyl Ester

[3904] ##STR00759##

[3905] Under the same conditions as the method for synthesizing Compound B2-22-1, the title compound was prepared from Compound K6 and 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester.

[3906] LCMS: m/z 498 [M+H].sup.+

[3907] HPLC retention time: 4.24 min (analysis condition W)

Example 745

Compound K7-6

9-Methoxy-6,6-dimethyl-11-oxo-8-(1,2,3,6-tetrahydro-pyridin-4-yl)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[3908] ##STR00760##

[3909] Under the same conditions as the method for synthesizing Compound A8-1, the title compound was prepared from K7-5.

[3910] LCMS: m/z 398 [M+H].sup.+

[3911] HPLC retention time: 2.57 min (analysis condition W)

Example 746

Compound K8-1

8-(1-Cyclobutyl-1,2,3,6-tetrahydro-pyridin-4-yl)-9-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[3912] ##STR00761##

[3913] Under the same conditions as the method for synthesizing Compound B3-32, the title compound was prepared from Compound K7-6 and cyclobutanone.

[3914] LCMS: m/z 452 [M+H].sup.+

[3915] HPLC retention time: 2.72 min (analysis condition W)

Example 747

Compound K8-2

8-(1-Cyclobutyl-piperidin-4-yl)-9-methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[3916] ##STR00762##

[3917] Under the same conditions as the method for synthesizing Compound B3-13-1, the title compound was prepared from Compound K8-1.

[3918] LCMS: m/z 454 [M+H].sup.+

[3919] HPLC retention time: 2.76 min (analysis condition W)

Example 748

Compound K9-5

8-(1-Cyclobutyl-piperidin-4-yl)-9-hydroxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[3920] ##STR00763##

[3921] Under the same conditions as the method for synthesizing Compound E3-2, the title compound was prepared from Compound K8-2.

[3922] LCMS: m/z 440 [M+H].sup.+

[3923] HPLC retention time: 2.57 min (analysis condition W)

Example 749

Compound K10-8

8-(1-Cyclobutyl-piperidin-4-yl)-9-isopropoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[3924] ##STR00764##

[3925] Under the same conditions as the method for synthesizing Compound A7-17, the title compound was prepared from Compound K9-5 and isopropyl iodide.

[3926] LCMS: m/z 482 [M+H].sup.+

[3927] HPLC retention time: 1.74 min (analysis condition S)

[3928] The compounds described in the following Tables 2-3 were synthesized from the intermediates of Compound K or Compound L by alkylation of hydroxyl group according to Mitsunobu reaction used for preparing Compound A7-1 or the method used for the synthesis of Compound A7-17 (described in the Table).

TABLE-US-00002 TABLE 2 Example Comp. HPLC Retention No. No. Structure Compound Name Condition Time m/z Method 750 K10-9 [00765] 6,6-Dimethyl- 8-(4-morpholin- 4-yl-piperidin-1-yl)- 11-oxo- 9-(tetrahydro- pyran-4-yloxy)- 6,11-dihydro-5H- benzo[b]carbazole- 3-carbonitrile U 1.35 555 A7-1 751 K10-10 [00766] 9-(2-Methoxy- ethoxy)-5-(2- methoxy-ethyl)- 6,6-dimethyl-8-(4- morpholin-4-yl- piperidin-1-yl)-11- oxo-6,11-dihydro- 5H- benzo[b]carbazole- 3-carbonitrile S 1.50 587 A7-17 752 K10-11 [00767] 9-(2-Methoxy- ethoxy)-6,6- dimethyl-8-(4- morpholin-4-yl- piperidin-1-yl)-11- oxo-6,11-dihydro- 5H- benzo[b]carbazole- 3-carbonitrile S 1.37 529 A7-17 753 K10-12 [00768] 9-Ethoxy-6,6- dimethyl-8-(4- morpholin-4-yl- piperidin-1-yl)-11- oxo-6,11-dihydro- 5H- benzo[b]carbazole- 3-carbonitrile U 1.95 499 A7-17 754 K10-13 [00769] 6,6-Dimethyl-8-(4- morpholin-4-yl- piperidin-1-yl)-11- oxo-9-(tetrahydro- furan-3-yloxy)- 6,11-dihydro-5H- benzo[b]carbazole- 3-carbonitrile S 1.40 541 A7-1 755 K10-14 [00770] 9-(2-Diethylamino- ethoxy)-6,6- dimethyl-8-(4- morpholin-4-yl- piperidin-1-yl)-11- oxo-6,11-dihydro- 5H- benzo[b]carbazole- 3-carbonitrile S 1.13 570 A7-17 756 K10-15 [00771] 8-(4-Cyclobutyl- piperazin-1-yl)-9- (2-methoxy- ethoxy)-6,6- dimethyl-11-oxo- 6,11-dihydro-5H- benzo[b]carbazole- 3-carbonitrile S 1.45 499 A7-17 757 K10-16 [00772] 8-(4-Cyclobutyl- piperazin-1-yl)- 5,6,6-trimethyl-11- oxo-9-(tetrahydro- furan-3-yloxy)- 6,11-dihydro-5H- benzo[b]carbazole- 3-carbonitrile S 1.98 525 A7-1 758 K10-17 [00773] 8-(4-Cyclobutyl- piperazin-1-yl)-9- (1-ethyl-propoxy)- 5,6,6-trimethyl-11- oxo-6,11-dihydro- 5H- benzo[b]carbazole- 3-carbonitrile S 2.43 525 A7-1 759 K10-18 [00774] 8-(4-Cyclobutyl- piperazin-1-yl)- 6,6-dimethyl-11- oxo-9- (tetrahydro-furan- 3-yloxy)-6,11- dihydro-5 H- benzo[b]carbazole- 3-carbonitrile S 1.92 511 A7-1 760 K10-19 [00775] 8-(4-Cyclobutyl- piperazin-1-yl)-6,6- dimethyl-11-oxo-9- (tetrahydro-pyran- 4-yloxy)-6,11- dihydro-5H- benzo[b]carbazole- 3-carbonitrile U 1.97 525 A7-1 761 K10-20 [00776] 8-(4-Cyclobutyl- piperazin-1-yl)-9- (1-ethyl-propoxy)- 6,6-dimethyl-11- oxo-6,11-dihydro- 5H- benzo[b]carbazole- 3-carbonitrile S 1.32 511 A7-1 762 L10-3 [00777] 9-Isopropoxy-8-(2- methoxy-ethoxy)- 5-(2-methoxy- ethyl)-6,6- dimethyl-11-oxo- 6,11-dihydro-5H benzo[b]carbazole- 3-carbonitrile S 2.68 477 A7-17 763 L10-4 [00778] 9-Isopropoxy-8-(2- methoxy-ethoxy)- 6,6-dimethyl-11- oxo-6,11-dihydro- 5H- benzo[d]carbazole- 3-carbonitrile S 2.68 419 A7-17

TABLE-US-00003 TABLE 3 Example Comp. HPLC Retention No. No. Structure Compound Name Condition Time m/z Method 764 L10-5 [00779] 8-(1-Cyclobutyl- piperidin-4- ylmethoxy)-9- isopropoxy-6,6- dimethyl-11-oxo- 6,11-dihydro-5H- benzo[d]carbazole- 3-carbonitrile S 1.65 512 A7-1 765 L10-6 [00780] 9-Isopropoxy-8-(1- isopropyl-piperidin- 4-ylmethoxy)-6,6- dimethyl-11-oxo- 6,11-dihydro-5H- benzo[b]carbazole- 3-carbonitrile S 1.62 500 A7-1 766 L10-7 [00781] 8-(1-Cyclobutyl- piperidin-3-yloxy)- 9-isopropoxy-6,6- dimethyl-11-oxo- 6,11-dihydro-5H- benzo[b]carbazole- 3-carbonitrile S 1.65 498 A7-1 767 L10-8 [00782] 9-Isopropoxy-8-(1- isopropyl-piperidin- 3-yloxy)-6,6- dimethyl-11-oxo- 6,11-dihydro-5H- benzo[b]carbazole- 3-carbonitrile S 1.59 486 A7-1 768 L10-9 [00783] 8-(2-Diethylamino- ethoxy)-9- isopropoxy-6,6- dimethyl-11-oxo- 6,11-dihydro-5H- benzo[b]carbazole- 3-carbonitrile U 2.07 460 A7-17 769 L10-10 [00784] 9-Isopropoxy-6,6- dimethyl-11-oxo-8- (pyridin-4-yloxy)- 6,11-dihydro-5H- benzo[b]carbazole- 3-carbonitrile U 2.07 438 A7-17 770 L10-11 [00785] 9-Isopropoxy-6,6- dimethyl-11-oxo-8- vinyloxy-6,11- dihydro-5H- benzo[b]carbazole- 3-carbonitril U 2.77 387 A7-17 771 L10-12 [00786] 9-Isopropoxy-6,6- dimethyl-11-oxo-8- (tetrahydro-furan- 3-yloxy)-6,11- dihydro-5H- benzo[d]carbazole- 3-carbonitrile S 2.45 431 A7-1

[3929] The compounds described in the following Table 4 were synthesized from the intermediates of Compound B according to the method described in the Table.

TABLE-US-00004 TABLE 4 Example Comp. HPLC Retention No. No. Structure Compound Name Condition Time m/z Method 772 B3-39 [00787] 8-((3R,5S)-4- Cyclobutyl-3,5- dimethyl-piperazin-1- yl)-6,6-dimethyl-11- oxo-6,11-dihydro-5H- benzo[b]carbazole-3- carbonitrile U 1.90 453 B3-32 773 B3-40 [00788] 8-((3R,5S)-4-Ethyl- 3,5-dimethyl-piperazin- 1-yl)-6,6-dimethyl-11- oxo-6,11-dihydro-5H- benzo[b]carbazole-3- carbonitrile U 1.82 427 B3-32 774 B2-30 [00789] 6,6-Dimethyl-8-[4-(1- methyl-piperidin-4-yl)- piperazin-1-yl]-11-oxo- 6,11-dihydro-5H- benzo[b]carbazole-3- carbonitrile U 1.58 468 B2-1 775 B3-41 [00790] 8-(4- Cyclobutanecarbonyl- piperazin-1-yl)-6,6- dimethyl-11-oxo-6,11- dihydro-5H- benzo[b]carbazole-3- carbonitrile U 2.35 453 A9-10 776 B3-42 [00791] 8-(4- Cyclopropanecarbonyl- piperazin-1-yl)-6,6- dimethyl-11-oxo-6,11- dihydro-5H- benzo[b]carbazole-3- carbonitrile U 2.22 439 A9-10

Example 777

Compound E6-4

9-Ethyl-8-hydroxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[3930] ##STR00792##

[3931] Under the same conditions as the method for synthesizing Compound E3-2, the title compound was prepared from Compound E5-1.

[3932] LCMS: m/z 331 [M+H].sup.+

[3933] HPLC retention time: 3.42 min (analysis condition W)

Example 778

Compound E7

Trifuloro-methanesulfonic acid 3-cyano-9-ethyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazol-8-yl Ester

[3934] ##STR00793##

[3935] Under the same conditions as the method for synthesizing Compound B1, the title compound was prepared from Compound E6-4.

[3936] LCMS: m/z 463 [M+H].sup.+

[3937] HPLC retention time: 4.39 min (analysis condition W)

Example 779

Compound E8-1

9-Ethyl-6,6-dimethyl-11-oxo-8-piperazin-1-yl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[3938] ##STR00794##

[3939] The title compound was prepared from Compound E7 and piperazine in the same manner as the method for synthesizing Compound B2-1.

[3940] LCMS: m/z 399 [M+H].sup.+

[3941] HPLC retention time: 1.88 min (analysis condition U)

Example 780

Compound E8-2

9-Ethyl-6,6-dimethyl-8-((S)-3-methyl-piperazin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[3942] ##STR00795##

[3943] Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound E7 and 2-(S)-methylpiperazine.

[3944] LCMS: m/z 413 [M+H].sup.+

[3945] HPLC retention time: 2.76 min (analysis condition W)

Example 781

Compound E8-3

8-((3R,5S)-3,5-Dimethyl-piperazin-1-yl)-9-ethyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[3946] ##STR00796##

[3947] Under the same conditions as the method for synthesizing Compound B2-1, the title compound was prepared from Compound E7 and cis-2,6-dimethylpiperazine.

[3948] LCMS: m/z 427 [M+H].sup.+

[3949] HPLC retention time: 2.00 min (analysis condition U)

Example 782

Compound E8-4

8-(1-Cyclobutyl-1,2,3,6-tetrahydro-pyridin-4-yl)-9-ethyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[3950] Compound 7 was converted in the same manner as Compound B2-22-1 and Compound 2, and subsequently subjected to reductive amination in the same manner as Compound B3-32 to obtain the title compound.

##STR00797##

[3951] LCMS: m/z 450 [M+H].sup.+

[3952] HPLC retention time: 2.12 min (analysis condition U)

Example 783

Compound E9-1

8-((S)-4-Cyclobutyl-3-methyl-piperazin-1-yl)-9-ethyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[3953] ##STR00798##

[3954] Under the same conditions as the method for synthesizing Compound B3-32, the title compound was prepared from Compound E8-2 and cyclobutanone.

[3955] LCMS: m/z 467 [M+H].sup.+

[3956] HPLC retention time: 2.90 min (analysis condition W)

[3957] The compounds described in the following Table 5 were prepared by acylation from Compound E8-1 in the same manner as the method for synthesizing Compound A9-10.

TABLE-US-00005 TABLE 5 Example Comp. HPLC Retention No. No. Structure Compound Name Condition Time m/z 784 E9-2 [00799] 8-(4- Cyclopropanecarbonyl- piperazin-1-yl)-9-ethyl- 6,6-dimethyl-11-oxo- 6,11-dihydro-5H- benzo[b]carbazole-3- carbonitrile U 2.58 467 785 E9-3 [00800] 8-(4- Cyclobutanecarbonyl- piperazin-1-yl)-9-ethyl- 6,6-dimethyl-11-oxo- 6,11-dihydro-5H- benzo[b]carbazole-3- carbonitrile U 2.74 481 786 E9-4 [00801] 8-[4-(2- Dimethylamino-acetyl)- piperazin-1-yl]-9-ethyl- 6,6-dimethyl-11-oxo- 6,11-dihydro-5H- benzo[b]carbazole-3- carbonitrile U 1.98 484 787 E9-5 [00802] 9-Ethyl-8-(4-isobutyryl- piperazin-1-yl)-6,6- dimethyl-11-oxo-6,11- dihydro-5H- benzo[b]carbazole-3- carbonitrile U 2.67 469 788 E9-6 [00803] 8-(4-Acetyl-piperazin- 1-yl)-9-ethyl-6,6- dimethyl-11-oxo-6,11- dihydro-5H- benzo[b]carbazole-3- carbonitrile U 2.35 441 789 E9-7 [00804] 8-(4- Cyclopentanecarbonyl- piperazin-1-yl)-9-ethyl- 6,6-dimethyl-11-oxo- 6,11-dihydro-5H- benzo[b]carbazole-3- carbonitrile S 2.87 495 790 E9-8 [00805] 8-(4- Cyclohexanecarbonyl- piperazin-1-yl)-9-ethyl- 6,6-dimethyl-11-oxo- 6,11-dihydro-5H- benzo[b]carbazole-3- carbonitrile S 2.97 509

Example 791

Compound E9-9

8-[4-(1-Cyano-cyclohexyl)-piperazin-1-yl]-9-ethyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[3958] ##STR00806##

[3959] 9-Ethyl-6,6-dimethyl-11-oxo-8-piperazin-1-yl-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (45 mg) and cyclohexanone (25 mg) were suspended in chloroform (2 ml), added with trimethylsilyl cyanide (30 mg) and zinc iodide (5 mg), and the mixture was stirred at 60 C. for 17 hrs. The reaction mixture was diluted with ethyl acetate (20 ml) and the organic layer was washed with 10% brine solution and concentrated under reduced pressure. The resulting residues were purified by silica gel column (dichloromethane/methanol (=99/1)) to obtain the title compound (12 mg, yield 30%).

[3960] LCMS: m/z 506 [M+H].sup.+

[3961] HPLC retention time: 3.00 min (analysis condition U)

[3962] The compounds described in the following Table 6 were synthesized from Compound E8-1 or Compound PR10-1 in the same manner as the method for Compound E9-9.

TABLE-US-00006 TABLE 6 Example Comp. HPLC Retention No. No. Structure Compound Name Condition Time m/z 792 E9-10 [00807] 8-[4-(1-Cyano- cyclobutyl)-piperazin- 1-yl]-9-ethyl-6,6- dimethyl-11-oxo-6,11- dihydro-5H- benzo[b]carbazole-3- carbonitrile U 2.88 478 793 PR11-20 [00808] 8-(4-Cyano-4- hydroxy-piperidine-1- yl)-9-ethyl-6,6- dimethyl-11-oxo-6,11- dihydro-5H- benzo[b]carbazole-3- carbonitrile Y 3.05 439 794 PR11-21 [00809] 8-(4-Cyano-4- morpholine-4-yl- piperidine-1-yl)-9- ethyl-6,6-dimethyl-11- oxo-6,11-dihydro-5H- benzo[b]carbazole-3- carbonitrile Y 3.35 508

[3963] With respect to the compounds described in the following Table 7, Compound F2 was subjected to amination in the same manner as Compound B2-1. Subsequently, the preparation was carried out by reductive amination in the same manner as the method for Compound B3-32.

TABLE-US-00007 TABLE 7 Example Comp. HPLC Retention No. No. Structure Compound Name Condition Time m/z Method 795 F3-12 [00810] 9-Bromo-8-((3R,5S)- 3,5-dimethyl- piperazin-1-yl)-6,6- dimethyl-11-oxo-6,11- dihydro-5H- benzo[b]carbazole-3- carbonitrile U 2.05 477,479 B2-1 796 F4-11 [00811] 9-Bromo-8-((3R,5S)- 4-cyclobutyl-3,5- dimethyl-piperazin-1- yl)-6,6-dimethyl-11- oxo-6,11-dihydro-5H- benzo[b]carbazole-3- carbonitrile U 2.28 531,533 B3-32

Example 797

Compound PR1

2-(4-Vinylphenyl)-2-methylpropanoic Acid

[3964] ##STR00812##

[3965] 2-(4-Bromophenyl)-2-methylpropanoic acid (30 g), PPh.sub.3 (5.0 g), potassium vinyltrifluoroborate (24.8 g), potassium carbonate (51.2 g), and palladium acetate (1.43 g) were dissolved in 1-propanol (198 ml) and distilled water (99 ml). After deaeration, the mixture was stirred under reflux for 6 hrs under nitrogen atmosphere. Insoluble matters were removed by filtration and washed with 1-propanol (210 ml). The filtrate was then concentrated under reduced pressure. Concentrated residues were partitioned between CPME (300 ml) and distilled water (150 ml, comprising 4.17 ml of ethylenediamine). The organic layer was removed and the aqueous layer was adjusted to pH 5 by using 2 N hydrochloric acid. The aqueous layer was extracted with a mixture of isopropyl acetate (240 ml) and heptane (240 ml). The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. Ethanol (300 ml) was added thereto for suspending and washing the resultant. The solid was removed by Celite filtration, and the filtrate was concentrated under reduced pressure to obtain the title compound (21.7 g, 93%).

[3966] .sup.1H-NMR (400 MHz CDCl.sub.3) ppm 7.49-7.34 (4H, m), 6.69 (1H, dd, J=17.6, 11.0 Hz), 5.72 (1H, d, J=17.6 Hz), 5.23 (1H, d, 11.0 Hz), 1.59 (s, 6H)

[3967] HPLC retention time: 2.05 min (analysis condition S)

Example 798

Compound PR2

2-(4-Ethylphenyl)-2-methylpropanoic Acid

[3968] ##STR00813##

[3969] 2-(4-Vinylphenyl)-2-methylpropanoic acid (58 g) was dissolved in ethanol, and then stirred for 3 hrs under atmospheric hydrogen pressure in the presence of 10% palladium carbon (5.8 g). The catalyst was removed by filtration, and the filtrate was concentrated to obtain a crude product, which was then suspended and washed with hexane to give the title compound (56.5 g, 94.8%).

[3970] .sup.1H-NMR (270 MHz DMSO-d.sub.6) ppm 12.28 (1H, s), 7.27-7.22 (2H, m), 7.18-7.14 (2H, m), 2.56 (2H, q, J=7.6 Hz), 1.45 (6H, s), 1.16 (3H, t, J=7.6 Hz)

[3971] LCMS: m/z 193 [M+H].sup.+

[3972] HPLC retention time: 2.18 min (analysis condition S)

Example 799

Compound PR3

2-(4-Ethyl-3-iodophenyl)-2-methylpropanoic Acid

[3973] ##STR00814##

[3974] 2-(4-Ethylphenyl)-2-methylpropanoic acid (58.1 g, 302.2 mmol) was dissolved in acetic acid (175 ml), added with N-iodosuccinimide (71.4 g, 317.3 mmol, 1.05 eq.) and conc. sulfuric acid (75 ml) at 0 C. Thereafter, the mixture was stirred at room temperature for 2 hrs. After cooling the reaction solution to 0 C., 10% aqueous solution of sodium hydrogen sulfite (100 ml) was added and the mixture was stirred for 1 hr. H.sub.2O (450 ml) was added to the mixture and the precipitated solid was filtered to obtain the title compound as a crude product. Ethanol (150 ml) and 10% aqueous solution of sodium hydrogen sulfite (50 ml) were added to the crude product, and the mixture was dissolved under heating at 50 C. After confirming the dissolution, the solution was cooled to room temperature, added with H.sub.2O (300 ml), and then stirred at 0 C. for 1 hr. The precipitated solid was filtered to obtain the title compound (95.8 g, 99%).

[3975] .sup.1H-NMR (270 MHz DMSO-d.sub.6) ppm 12.46 (1H, s), 7.70 (1H, d, J=1.8 Hz), 7.32 (1H, dd, J=8.1, 1.8 Hz), 7.26 (1H, d, J=8.1 Hz), 2.64 (2H, q, J=7.5 Hz), 1.43 (6H, s), 1.12 (3H, t, J=7.5 Hz)

[3976] HPLC retention time: 2.53 min (analysis condition S)

Example 800

Compound PR4

Tert-butyl 4-(4-ethyl-3-iodophenyl)-4-methyl-3-oxopentanoic Acid

[3977] ##STR00815##

[3978] Mono-tert-butyl malonic acid (72.5 g) was dissolved in DME (360 ml), added with TEA (189 ml) and magnesium chloride (29.63 g) and the mixture was stirred for 2 hrs. In a separate vessel, CDI (52.75 g) was added to the DME (360 ml) solution of 2-(4-ethyl-3-iodophenyl)-2-methylpropanoic acid (90 g) and stirred at room temperature for 1 hr to prepare a solution. This solution was then added dropwise to the aforementioned mixture, and the resulting solution was washed with DME (90 ml) and stirred at 70 C. for 3 hrs. The reaction mixture was diluted with isopropyl acetate (225 ml) and heptane (225 ml), and the organic layer was washed with 2 N hydrochloric acid (684 ml), 0.17 N hydrochloric acid (540 ml), 15% aqueous solution of ammonium chloride (540 ml), 1 N aqueous solution of sodium hydroxide (540 ml) and 15% brine (540 ml) in order. The organic layer was concentrated under reduced pressure to obtain the title compound as a crude product, which was used for the next step without further purification.

[3979] .sup.1H-NMR (270 MHz DMSO-d.sub.6) : 7.64 (1H, d, J=2.0 Hz), 7.30 (1H, d, J=8.1 Hz), 7.24 (1H, d, J=8.0, 2.0 Hz), 3.32 (2H, s), 2.65 (2H, q, J=7.4 Hz), 1.40 (6H, s), 1.34 (9H, s), 1.13 (3H, t, J=7.4 Hz)

Example 801

Compound PR5-1

Tert-butyl 6-cyano-2-(2-(4-ethyl-3-iodophenyl)propan-2-yl)-1H-indole-3-carboxylic Acid

[3980] ##STR00816##

[3981] 4-(4-Ethyl-3-iodophenyl)-4-methyl-3-oxopentanoic acid tert-butyl (117.76 g) was dissolved in DMF (471 ml) and added with cesium carbonate (276.5 g). DMF solution (176.6 ml) of 4-chloro-3-nitrobenzonitrile (63.9 g) was added dropwise thereto (washed with DMF 58.8 ml), and the mixture was stirred at 35 C. for 6 hrs. To the mixture, THF (588.8 ml), ethyl acetate (588.8 ml), acetic acid (72.87 ml) and distilled water (588.8 ml) were added for distribution, and the aqueous layer was removed. The organic layer was added with THF (588.8 ml) and water (588.8 ml), and under stirring sodium hydrosulfite (80%, 147.76 g) was added in small portions and the mixture was stirred at room temperature for 3 hrs. After removing the aqueous layer, the organic layer was washed with 15% brine (588.8 ml). The organic layer was added with 1 N hydrochloric acid (94.2 ml), stirred for 1 hr, and then added with 1 N aqueous solution of sodium hydroxide (329.7 ml). The aqueous layer was removed and the organic layer was concentrated under reduced pressure. The concentrated residues were dissolved in ethanol (824.3 ml) and added dropwise with distilled water (247.3 ml). The resulting precipitated crystals were filtered and collected, washed with water:ethanol (=1:2 mixture solution, 588.8 ml), and then dried to obtain the title compound (98.12 g, two-step 63.5%).

[3982] .sup.1H-NMR (270 MHz DMSO-d.sub.6) : 12.04 (1H, br. s), 8.01 (1H, d, J=8.4 Hz), 7.91 (1H, d, J=0.8 Hz), 7.55 (1H, d, J=1.8 Hz), 7.49 (1H, dd, J=1.5, 8.4 Hz), 7.16 (1H, d, J=8.1 Hz), 7.07 (1H, dd, J=2.0, 8.1 Hz), 2.58 (2H, q, J=7.4 Hz), 1.79 (6H, s), 1.23 (9H, s), 1.06 (3H, t, J=7.4 Hz)

[3983] LCMS: m/z 459, 515 [M+H].sup.+

Example 802

Compound PR5-2

Methyl 6-cyano-2-(2-(4-ethyl-3-iodophenyl)propan-2-yl)-1H-indole-3-carboxylic Acid

[3984] ##STR00817##

[3985] The title compound was prepared from monomethyl malonate and 2-(4-ethyl-3-iodophenyl)-2-methylpropanoic acid in the same manner as the method for Compound PR4 and Compound PR5-1.

[3986] .sup.1H-NMR (270 MHz DMSO-D.sub.6) : 12.20 (s, 1H), 8.06-8.03 (m, 1H), 7.95-7.94 (m, 1H), 7.58-7.57 (m, 1H), 7.53-7.49 (m, 1H), 7.17-7.14 (m, 1H), 7.06-7.02 (m, 1H), 3.46 (s, 3H), 2.65-2.56 (q, 2H, J=7.5 Hz), 1.78 (s, 6H), 1.12-1.07 (t, 3H, J=7.5 Hz)

[3987] LCMS: m/z 473 [M+H].sup.+

Example 803

Compound PR6

Tert-Butyl 6-cyano-2-(2-(4-ethyl-3-(4-morpholin-4-yl-piperidin-1-yl)phenyl)propan-2-yl)-1H-indole-3-carboxylic Acid Hydrochloric Acid Salt

[3988] ##STR00818##

[3989] Tert-butyl 6-cyano-2-(2-(4-ethyl-3-iodophenyl)propan-2-yl)-1H-indole-3-carboxylic acid (390.5 g), 4-morpholin-4-yl piperidine (158 g), and 1,3-bis-(2,6-diisopropylphenyl)-imidazoyl-2-ylidene (allyl) palladium (II) chloride (8.83 g) were dissolved in a mixture of NaHMDS (1.9 M, THF solution 1.32 L) and DME (1.95 L) under nitrogen stream, and the mixture was stirred at 40 C. for 1 hr. The reaction mixture was then partitioned between isopropyl acetate (1.95 L) and 20% aqueous solution of ammonium chloride (1.95 L). The organic layer was washed twice with 10% brine (1.56 L), and then concentrated under reduced pressure. The resulting residues were dissolved in a mixture of DME (3.9 L) and water (78.1 ml), added with N-acetylcysteine (12.39 g), and stirred at 45 C. for 1 hr. After that, the insoluble matters were filtered and washed with DME (1.95 L). The filtrate was concentrated under reduced pressure. The resulting residues were dissolved in acetone (5.5 L) and added with the solution in which pyridinium chloride (96.5 g) is dissolved in acetone (195 ml) and ethanol (78 ml). The precipitated solid was filtered, collected, washed with acetone (1.95 L) and dried to obtain the title compound (373 g, 83%).

[3990] .sup.1H-NMR (400 MHz DMSO-D.sub.6) : 12.03 (1H, s), 10.75-10.88 (1H, m), 7.99 (1 H, d, J=8.3 Hz), 7.93 (1H, d, J=1.3 Hz), 7.46 (1H, dd, J=1.3, 8.1 Hz), 7.10 (1H, d, J=7.9 Hz), 6.88 (1H, dd, J=1.7, 7.9 Hz), 6.79 (1H, d, J=1.7 Hz), 3.91-4.01 (2H, m), 3.76-3.87 (2H, m), 3.37-3.46 (2H, m), 3.22 (1H, m), 2.94-3.11 (4H, m), 2.57 (2H, q, J=7.5 Hz), 2.45-2.53 (2H, m), 2.09-2.16 (2H, m), 1.80 (6H, s), 1.71-1.77 (2H, m), 1.19 (9H, s), 1.14 (3H, t, J=7.5 Hz)

[3991] LCMS: m/z 557 [M+H].sup.+

Example 804

Compound PR7

6-Cyano-2-(2-(4-ethyl-3-(4-morpholin-4-yl-piperidin-1-yl)phenyl)propan-2-yl)-1H-indole-3-carboxylic Acid

[3992] ##STR00819##

[3993] Tert-butyl 6-cyano-2-(2-(4-ethyl-3-(4-morpholin-4-yl-piperidin-1-yl)phenyl)propan-2-yl)-1H-indole-3-carboxylic acid hydrochloric acid salt (1400 g) was suspended in TFE (7 L) under nitrogen stream, and added dropwise with TMSCl (554 ml) at 8 C. After stirring for 3 hrs, the reaction solution was added with acetone (5.6 L) and aqueous solution of NaOH (1 N, 4.39 L), and 10% aqueous solution of K.sub.2HPO.sub.4 (1.4 L) was added thereto for neutralization. The precipitated solid was filtered and collected, washed twice with a mixture solution of water:acetone (=1:1, 2.8 L), and dried to obtain the title compound (1061 g, 96.6%).

[3994] .sup.1H-NMR (270 MHz DMSO-D.sub.6) : 11.95 (1H, s), 11.92 (1H, bs), 8.04 (1H, d, J=8.4 Hz), 7.89 (1H, d, J=1.3 Hz), 7.44 (1H, J=dd, 1.3, 8.4 Hz), 7.00 (1H, d, J=8.4 Hz), 6.88 (1H, d, J=1.8 Hz), 6.71 (1H, dd, J=2.2, 7.9 Hz), 3.50-3.55 (4H, m), 2.92-2.96 (2H, m), 2.54 (2H, q, 7.5 Hz), 2.39-2.50 (6H, m), 2.15-2.22 (1H, m), 1.74-1.85 (8H, m), 1.43-1.52 (2H, m), 1.13 (3H, t, J=7.5 Hz)

[3995] LCMS: m/z 501 [M+H].sup.+

[3996] HPLC retention time: 1.53 min (analysis condition U)

Example 805

Compound F6-20

9-Ethyl-6,6-dimethyl-8-(4-morpholin-4-yl-piperidin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[3997] ##STR00820##

[3998] 6-Cyano-2-(2-(4-ethyl-3-(4-morpholin-4-yl-piperidin-1-yl)phenyl)propan-2-yl)-1H-indole-3-carboxylic acid (500 g) was dissolved in a mixture of DMA (9.4 L), acetic anhydride (270 ml) and DIPEA (1170 ml) under nitrogen stream. The mixture was stirred at 90 C. for 1 hr. After cooling to room temperature, the mixture was added with methanol (3.525 L) and subsequently with distilled water (5.875 L). The precipitated solid was filtered, collected, washed twice with the mixture solution (methanol:water=3:5, 1.41 L), and then dried to obtain the title compound (389.6 g, 85%).

[3999] .sup.1H-NMR (400 MHz, DMSO-d.sub.6) : 12.70 (1H, s), 8.32 (1H, d, J=7.9 Hz), 8.04 (1H, s), 8.00 (1H, s), 7.61 (1H, d, J=8.5 Hz), 7.34 (1H, s), 3.64-3.57 (4H, m), 3.27-3.18 (2H, m), 2.82-2.66 (4H, m), 2.39-2.28 (1H, m), 1.96-1.87 (2H, m), 1.76 (6H, s), 1.69-1.53 (2H, m), 1.29 (3H, t, J=7.3 Hz)

[4000] LCMS: m/z 483 [M+H].sup.+

[4001] HPLC retention time: 1.98 min (analysis condition U)

[4002] Hydrochloric Acid Salt of Compound F6-20

[4003] 9-Ethyl-6,6-dimethyl-8-(4-morpholin-4-yl-piperidin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (400 g) was dissolved in a mixture solvent of methylethyl ketone (4.8 L), acetic acid (1.44 L) and distilled water (1.68 L) at room temperature. The resulting solution was added dropwise to the mixture of ethanol (12 L) and 2 N hydrochloric acid (0.8 L). The precipitated solid was filtered, washed with ethanol (2 L), and dried to obtain hydrochloric acid salt of Compound F6-20 (357 g).

[4004] .sup.1H-NMR (400 MHz, DMSO-d.sub.6) : 12.83 (1H, s), 10.78 (1H, s), 8.32 (1H, d, J=8.1 Hz), 8.06 (1H, s), 8.01 (1H, s), 7.61 (1H, d, J=8.1 Hz), 7.37 (1H, s), 4.02 (2H, m), 3.85 (2H, m), 3.51 (2H, m), 3.34 (1H, m), 3.32 (2H, m), 3.15 (2H, m), 2.81 (2H, dd, J=11.98, 11.7 Hz), 2.72 (2H, q, J=7.5 Hz), 2.23 (2H, m), 1.89 (2H, m), 1.77 (6H, s), 1.29 (3H, t, J=7.5 Hz)

[4005] FABMS: m/z 483.4 [M+H].sup.+

Example 806

Compound F6-22

9-Ethyl-6,6-dimethyl-10-(4-morpholin-4-yl-piperidin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[4006] ##STR00821##

[4007] From the filtrate solution obtained from the synthesis of Compound F6-20, the title compound was obtained.

[4008] .sup.1H-NMR (400 MHz DMSO-D.sub.6) : 12.56 (1H, s), 8.32 (1H, d, J=7.9 Hz), 7.96 (1H, s), 7.45-7.59 (3H, m), 3.55-3.62 (4H, m), 3.36-3.50 (2H, m), 2.75-2.86 (2H, m), 2.71 (2H, q, J=7.5 Hz), 2.45-2.56 (4H, m), 2.27-2.38 (1H, m), 1.73-1.84 (2H, m), 1.69 (6H, s), 1.43-1.58 (2H, m), 1.21 (3H, t, J=7.5 Hz).

[4009] LCMS: m/z 483 [M+H].sup.+

[4010] HPLC retention time: 1.52 min (analysis condition U)

Example 807

[4011] Compound PR8

9-Ethyl-6,6-dimethyl-8-iodo-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[4012] ##STR00822##

[4013] Tert-butyl 6-cyano-2-(2-(4-ethyl-3-iodophenyl)propan-2-yl)-1H-indole-3-carboxylic acid (11 g) was dissolved in Eaton's reagent (200 g) and stirred at room temperature for 30 min. The reaction solution was diluted with acetonitrile (200 ml) and distilled water (400 ml). The precipitated solid was collected by filtration, washed with distilled water, and then dried. The crude product was dissolved in DMA (45 ml), diluted with acetonitrile (20 ml) and distilled water (18 ml), and re-precipitated to obtain the title compound (6.62 g, 70%).

[4014] .sup.1H-NMR (400 MHz DMSO-D.sub.6) : 12.79 (1H, s), 8.32-8.29 (2H, m), 8.06 (1H, s), 8.01 (1H, s), 7.62 (1H, dd, J=1.3, 7.9 Hz), 2.78 (2H, q, J=7.5 Hz), 1.75 (6H, s), 1.20 (3H, t, J=7.5 Hz)

[4015] LCMS: m/z 441 [M+H].sup.+

[4016] HPLC retention time: 3.17 min (analysis condition U)

Example 808

Compound PR9-1

8-(1,4-Dioxa-8-aza-spiro[4.5]dec-8-yl)-9-ethyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[4017] ##STR00823##

[4018] The dioxane solution (50 ml) of 9-ethyl-6,6-dimethyl-8-iodo-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (5.0 g), 1,4-dioxa-8-aza-spiro[4.5]decane (2.08 ml), Pd.sub.2(dba).sub.3 (520 mg), and S-Phos (963 mg) was flushed with nitrogen gas, added with NaHMDS (1M, THF solution 40 ml), and stirred at 60 C. for 1 hr. The resulting mixture was diluted with ethyl acetate (200 ml). The organic layer was washed three times with 10% brine, and then concentrated under reduced pressure to obtain the title compound as a crude product. This crude product was used for the next step without further purification.

[4019] LCMS: m/z 456 [M+H].sup.+

[4020] HPLC retention time: 2.78 min (analysis condition U)

Example 809

Compound PR9-2

9-Ethyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[4021] ##STR00824##

[4022] As a by-product of Compound PR9-1, the target compound was obtained according to silica gel column separation of Example 810.

[4023] LCMS: m/z 315 [M+H].sup.+

[4024] HPLC retention time: 2.77 min (analysis condition U)

Example 810

Compound PR10-1

9-Ethyl-6,6-dimethyl-11-oxo-8-(4-oxopiperidin-1-yl)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[4025] ##STR00825##

[4026] 8-(1,4-Dioxa-8-aza-spiro[4.5]dec-8-yl)-9-ethyl-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile, which had been prepared in Example 809, was dissolved in THF (10 ml), added with 5 N hydrochloric acid (50 ml), and the mixture was stirred for 17 hrs. The reaction mixture was neutralized with 5 N aqueous solution of sodium hydroxide and diluted with ethyl acetate (200 ml). The organic layer was washed with 10% brine, and then concentrated under reduced pressure. The resulting residues were purified by silica gel column (dichloromethane/methanol=99/1 to 90/10) to obtain the title compound (2.9 g, two step yield 64%).

[4027] .sup.1H-NMR (400 MHz DMSO-D.sub.6) : 12.70 (1H, s), 8.32 (1H, d, J=8.4), 8.07 (1H, s), 7.99 (1H, s), 7.60 (1H, dd, J=1.3, 7.9 Hz), 7.42 (1H, s), 3.28 (4H, t, J=5.7), 2.80 (q, 2H, J=7.5 Hz), 2.55 (4H, t, J=5.7), 1.75 (6H, s), 1.31 (3H, t, J=7.5 Hz)

[4028] LCMS: m/z 412 [M+H].sup.+

[4029] HPLC retention time: 2.57 min (analysis condition U)

Example 811

Compound PR11-1

9-Ethyl-6,6-dimethyl-11-oxo-8-[4-(3-oxo-piperazin-1-yl)-piperidin-1-yl]-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[4030] ##STR00826##

[4031] 9-Ethyl-6,6-dimethyl-11-oxo-8-(4-oxopiperidin-1-yl)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (30 mg) and 2-ketopiperazine (10 mg) were dissolved in THF (2 ml), added with sodium triacetoxy borohydride (30 mg), and the mixture was stirred at 30 C. for 6 hrs. The reaction mixture was diluted with ethyl acetate (20 ml). The organic layer was washed with 10% brine, and then concentrated under reduced pressure. The resulting residues were purified by silica gel column (dichloromethane/methanol=99/1 to 90/10) to obtain the title compound (11.5 mg, yield 32%).

[4032] LCMS: m/z 496 [M+H].sup.+

[4033] HPLC retention time: 1.90 min (analysis condition U)

Example 812

Compound PR11-2

9-Ethyl-8-(4-hydroxy-piperidin-1-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[4034] ##STR00827##

[4035] As a by-product of Compound PR11-1, the target compound was obtained.

[4036] LCMS: m/z 414 [M+H].sup.+

[4037] HPLC retention time: 2.13 min (analysis condition S)

[4038] The compounds described in the following Tables 8-10 were synthesized by introducing a corresponding amine to 9-ethyl-6,6-dimethyl-8-iodo-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile according to the method used for the synthesis of Compound PR9-1. Although the relevant literatures are not entirely known, some amines in which a tertiary alkyl group is attached to the nitrogen atom were prepared according to the method described in Journal of Medicinal Chemistry, 45 (14), 3143-3160, 2002. Alternatively, the preparation was carried out by introducing a corresponding amine to 9-ethyl-6,6-dimethyl-11-oxo-8-(4-oxopiperidin-1-yl)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile based on the method that is used for the synthesis of Compound PR11-1 (i.e., reductive amination).

TABLE-US-00008 TABLE 8 Example HPLC Retention No. Comp. No. Structure Compound Name Condition Time m/z 813 PR9-3 [00828] 8-(4-tert-Butyl- piperazin-1-yl)-9- ethyl-6,6-dimethyl- 11-oxo-6,11- dihydro-5H- benzo[b]carbazole- 3-carbonitrile S 1.63 455 814 PR9-4 [00829] 9-Ethyl-6,6- dimethyl-11-oxo-8- (4-pyrrolidin-1-yl- piperidin-1-yl)- 6,11-dihydro-5H- benzo[b]carbazole- 3-carbonitrile U 2.13 467 815 PR9-5 [00830] 9-Ethyl-8-(4- isopropyl- piperazin-1-yl)-6,6- dimethyl-11-oxo- 6,11-dihydro-5H- benzo[b]carbazole- 3-carbonitrile U 2.08 441 816 PR9-6 [00831] 9-Ethyl-6,6- dimethyl-8-(4- methyl-piperazin- 1-yl)-11-oxo-6,11- dihydro-5H- benzo[b]carbazole- 3-carbonitrile U 1.97 413 817 PR9-7 [00832] 9-Ethyl-8-(4-ethyl- piperazin-1-yl)-6,6- dimethyl-11-oxo- 6,11-dihydro-5H- benzo[b]carbazole- 3-carbonitrile U 2.03 427 818 PR9-8 [00833] 9-Ethyl-6,6- dimethyl-8- morpholin-4-yl-11- oxo-6,11-dihydro- 5H- benzo[b]carbazole- 3-carbonitrile U 2.65 400 819 PR11-3 [00834] 8-[4-((2R,6S)-2,6- Dimethyl- morpholin-4-yl)- piperidin-1-yl]-9- ethyl-6,6-dimethyl- 11-oxo-6,11- dihydro-5H- benzo[b]carbazole- 3-carbonitrile S 1.65 511 820 PR11-4 [00835] 8- [1,4]Bipiperidinyl- 1-yl-9-ethyl-6,6- dimethyl-11-oxo- 6,11-dihydro-5H- benzo[b]carbazole- 3-carbonitrile S 1.63 481 821 PR11-5 [00836] 8-(4,4-Difluoro- [1,4]bipiperidinyl- 1-yl)-9-ethyl-6,6- dimethyl-11-oxo- 6,11-dihydro-5H- benzo[b]carbazole- 3-carbonilrile S 1.70 517 822 PR11-6 [00837] 8-(4-Azetidin-1-yl- piperidin-1-yl)-9- ethyl-6,6-dimethyl- 11-oxo-6,11- dihydro-5H- benzo[b]carbazole- 3-carbonitrile S 1.55 453 823 PR11-7 [00838] 9-Ethyl-8-(4- hydroxy- [1,4]bipiperidinyl- 1-yl)-6,6-dimethyl- 11-oxo-6,11- dihydro-5H- benzo[b]carbazole- 3-carbonitrile U 1.95 497 824 PR9-9 [00839] 8-(4-Cyclopropyl- 4-hydroxy- piperidin-1-yl)-9- ethyl-6,6-dimethyl- 11-oxo-6,11- dihydro-5H- benzo[b]carbazole- 3-carbonitrile U 2.53 454 825 PR11-8 [00840] 9-Ethyl-8-(4- fluoro- [1,4]bipiperidinyl- 1-yl)-6,6-dimethyl- 11-oxo-6,11- dihydro-5H- benzo[b]carbazole- 3-carbonitrile U 2.13 499 826 PR9-10 [00841] 9-Ethyl-6,6- dimethyl-8-(3- morpholin-4-yl- azetidin-1-yl)-11- oxo-6,11-dihydro- 5H- benzo[b]carbazole- 3-carbonitrile S 1.48 455

TABLE-US-00009 TABLE 9 Example Comp. HPLC Retention No. No. Structure Compound Name Condition Time m/z 827 PR9-11 [00842] 9-Ethyl-6,6- dimethyl-11-oxo-8- (3-piperidin-1-yl- azetidin-1-yl)-6,11- dihydro-5H- benzo[b]carbazole- 3-carbonitrile S 1.57 453 828 PR9-12 [00843] 9-Ethyl-6,6- dimethyl-8-[4-(1- methyl-piperidin-4- yl)-piperazin-1-yl]- 11-oxo-6,11- dihydro-5H- benzo[b]carbazole- 3-carbonitrile U 1.70 496 829 PR9-13 [00844] 9-Ethyl-6,6- dimethyl-8-[4-(4- methyl-piperazin- 1-yl)-piperidin-1- yl]-11-oxo-6,11- dihydro-5H- benzo[d]carbazole- 3-carbonitrile U 1.73 496 830 PR11-9 [00845] 8-(4-Cyclopentyl- piperazin-1-yl)-9- ethyl-6,6-dimethyl- 11-oxo-6,11- dihydro-5H- benzo[b]carbazole- 3-carbonitrile U 2.12 467 831 PR11-10 [00846] 9-Ethyl-8-[4-(2- hydroxy- ethylamino)- piperidin-1-yl]-6,6- dimethyl-11-oxo- 6,11-dihydro-5H- benzo[b]carbazole- 3-carbonitrile U 1.90 457 832 PR11-11 [00847] 9-Ethyl-8-[4-(3- hydroxy- propylamino)- piperidin-1-yl]-6,6- dimethyl-11-oxo- 6,11-dihydro-5H- benzo[d]carbazole- 3-carbonitrile S 1.90 471 833 PR9-14 [00848] 9-Ethyl-6,6- dimethyl-8-(4- methyl-4- morpholine-4-yl- piperidine-1-yl)-11- oxo-6,11-dihydro- 5H- benzo[b]carbazole- 3-carbonitrile U 2.00 497 834 PR9-15 [00849] 9-Ethyl-8-[4-(1- ethyl-cyclobutyl)- piperazine-l-yl]- 6,6-dimethyl-11- oxo-6,11-dihydro- 5H- benzo[b]carbazole- 3-carbonitrile Y 2.25 481 835 PR9-16 [00850] 9-Ethyl-8-(4- ethyl-4- morpholine-4-yl- piperidine-1-yl) 6,6-dimethyl-11- oxo-6,11-dihydro- 5H- benzo[b]carbazole- 3-carbonitrile Y 2.17 511 836 PR9-17 [00851] 3-Ethyl-8-(4- isopropyl-4- morpholine-4-yl- piperidine-1-yl)- 6.6-dimethyl-11- oxo-6,11-dihydro- 5H- benzo[b]carbazole- 3-carbonitrile U 2.12 525 837 PR9-18 [00852] 9-Ethyl-6,6- dimethyl-11-oxo-8- [4-(1-propyl- cyclobutyl)- piperazine-1-yl]- 6,11-dihydro-5H- benzo[b]carbazole- 3-carbonitrile U 2.23 495 838 PR9-19 [00853] 9-Ethyli-8-[4-(1- isopropyl- cyclobutyl)- piperazine-1-yl]- 6,6-dimethyl-11- oxo-6,11-dihydro- 5H- benzo[b]carbazole- 3-carbonrtrile U 2.25 495 839 PR9-20 [00854] 9-Ethyl-6,6- dimethyl-8-(2- morpholine-4-yl- ethylamino)-11- oxo-6,11-dihydro- 5H- benzo[b]carbazole- 3-carbonitrile Y 1.85 443 840 PR9-21 [00855] 9-Ethyl-6,6- dimethyl-11-oxo-8- (2-piperidine-1-yl- ethylamino)-6,11- dihydro-5H- benzo[b]carbazole- 3-carbonitrile Y 1.85 441

TABLE-US-00010 TABLE 10 Example Comp. HPLC Retention No. No. Structure Compound Name Condition Time m/z 841 PR11-12 [00856] 8-(4-Amino- piperidine-1-yl)-9- ethyl-6,6-dimethyl- 11-oxo-6,11-dihydro- 5H- benzo[b]carbazole-3- carbonitrile U 1.92 413 842 PR11-13 [00857] 9-Ethyl-6,6- dimethyl-8-(4- 2,2,3,3,5,5,6,6-d8- morpholine-4-yl- piperidine-1-yl)- 11-oxo-6,11- dihydro-5H-benzo [b]carbazole-3- carbonitrile U 1.98 491 843 PR9-22 [00858] 9-Ethyl-8-[4-(2- methoxy-ethoxy)- piperidine-1-yl]-6,6- dimethyl-11-oxo- 6,11-dihydro-5H- benzo[b]carbazole-3- carbonitrile Y 3.23 472 844 PR9-23 [00859] 8-[4-(2-Ethoxy- ethoxy)-piperidine-1- yl]-9-ethyl-6,6- dimethyl-11-oxo- 6,11-dihydro-5H- benzo[b]carbazole-3- carbonitrile Y 3.35 486 845 PR9-24 [00860] 8-(4- Cyclopropylmethoxy- piperidine-1-yl)-9- ethyl-6,6-dimethyl- 11-oxo-6,11-dihydro- 5H- benzo[b]carbazole-3- carbonitrile Y 3.50 463 846 PR9-25 [00861] 8-[4-(2-Cyclohexyl- ethoxy)-piperidine-1- yl]-9-ethyl-6,6- dimethyl-11-oxo- 6,11-dihydro-5H- benzo[b]carbazole-3- carbonitrile Y 4.00 524 847 PR11-14 [00862] 8-(4- Cyclohexylamino- piperidine-1-yl)-9- ethyl-6,6-dimethyl- 11-oxo-6,11-dihydro- 5H- benzo[b]carbazole-3- carbonitrile Y 2.33 495 848 PR11-15 [00863] 8-(4- Cyclopentylamino- piperidine-1-yl)-9- ethyl-6,6-dimethyl- 11-oxo-6,11-dihydro- 5H- benzo[b]carbazole-3- carbonitrile Y 2.15 481 849 PR11-16 [00864] 8-[4- (Cyclopropylmethyl- amino)-piperidine-1- yl]-9-ethyl-6,6- dimethyl-11-oxo- 6,11-dihydro-5H- benzo[b]carbazole-3- carbonitrile Y 2.15 467 850 PR11-17 [00865] 8-(4- Cyclopropylamino- piperidine-1-yl)-9- ethyl-6,6-dimethyl- 11-oxo-6,11-dihydro- 5H- benzo[b]carbazole-3- carbonitrile Y 2.08 453 851 PR11-18 [00866] 8-(4- Cyclobutylamino- piperidine-1-yl)-9- ethyl-6,6-dimethyl- 11-oxo-6,11-dihydro- 5H- benzo[b]carbazole-3- carbonitrile Y 2.13 457 852 PR11-19 [00867] 8-[4- (Cyclohexylmethyl- amino)-piperidine-1- yl]-9-ethyl-6,6- dimethyl-11-oxo- 6,11-dihydro-5H- benzo[b]carbazole-3- carbonitrile Y 2.42 509

Example 853

Compound PR11-22

9-Ethyl-8-(4-hydroxyimino-piperidin-1-yl)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[4039] ##STR00868##

[4040] 9-Ethyl-6,6-dimethyl-11-oxo-8-(4-oxopiperidin-1-yl)-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (30 mg) and hydroxylamine hydrochloric acid salt (10 mg) were dissolved in ethanol (5 ml) and stirred at 60 C. for 6 hrs. The reaction mixture was diluted with ethyl acetate (20 ml). The organic layer was washed with 10% brine and concentrated under reduced pressure. The resulting residues were purified by silica gel column (dichloromethane/methanol=99/1 to 90/10) to obtain the title compound (23.5 mg, yield 74%).

[4041] LCMS: m/z 427 [M+H].sup.+

[4042] HPLC retention time: 3.08 min (analysis condition Y)

Example 854

Compound PR10-2

9-Ethyl-6,6-dimethyl-5-(2-morpholin-4-yl-ethyl)-8-(2-morpholin-4-yl-ethylamino)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[4043] ##STR00869##

[4044] 9-Ethyl-6,6-dimethyl-8-(2-morpholin-4-yl-ethylamino)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (10 mg) was dissolved in DMF (1 ml), added with K.sub.2CO.sub.3 (10 mg) and 1-(2-chloroethyl)morpholine (8 mg), and then stirred at 90 C. for 17 hrs. The reaction mixture was diluted with ethyl acetate (10 ml). The organic layer was washed with 10% brine and concentrated under reduced pressure. The resulting residues were purified by silica gel column (dichloromethane/methanol=99/1 to 90/10) to obtain the title compound (6.4 mg, yield 58%).

[4045] LCMS: m/z 556 [M+H].sup.+

[4046] HPLC retention time: 1.78 min (analysis condition Y)

Example 855

Compound F7

9-Ethyl-6,6-dimethyl-11-oxo-8-[4-(4-oxy-morpholin-4-yl)-piperidin-1-yl]-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile

[4047] ##STR00870##

[4048] 9-Ethyl-6,6-dimethyl-8-(4-morpholin-4-yl-piperidin-1-yl)-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (400 mg) was dissolved in trifluoroethanol (80 ml), added with 30% hydrogen peroxide solution (0.8 ml), and the mixture was stirred at 60 C. for 17 hrs. The reaction mixture was concentrated to 30 ml and diluted with water (20 ml). The precipitated matter was collected by filtration and dried to obtain the title compound (375 mg, yield 90%).

[4049] LCMS: m/z 499 [M+H].sup.+

[4050] HPLC retention time: 2.05 min (analysis condition U)

Example 856

Compound FR1

6-Cyano-2-[1-(4-ethyl-3-iodophenyl)-1-methyl-ethyl]-benzofuran-3-carboxylic Acid Tert-Butyl Ester

[4051] ##STR00871##

[4052] 4-(4-Ethyl-3-iodo-phenyl)-4-methyl-3-oxo-pentanoic acid tert-butyl ester (1.00 g, 2.40 mmol) was dissolved in NMP (4 ml), added with cesium carbonate (1.56 g, 4.80 mmol, 2.0 eq.), and the mixture was stirred for 5 min. The NMP solution (2 ml) of 4-chloro-3-nitro-benzonitrile (542 mg, 2.88 mmol, 1.2 eq.) was added thereto, and the mixture was stirred at 50 C. for 64 hrs under nitrogen atmosphere. After cooling to room temperature, ethyl acetate (20 ml) was added and the organic layer was washed with saturated aqueous solution of ammonium chloride (20 ml). The organic layer was further washed with saturated brine and dried over sodium sulfate. The drying agent was removed by filtration and the residues obtained after concentration under reduced pressure were purified by silica gel column chromatography (ethyl acetate/hexane) to obtain the title compound (white amorphous, 320 mg, 26%).

[4053] LCMS: m/z 516 [M+H].sup.+

Example 857

Compound FR2

6-Cyano-2-{1-[4-ethyl-3-(4-morpholin-4-yl-piperidin-1-yl)-phenyl]-1-methyl-ethyl}-benzofuran-3-carboxylic Acid Tert-Butyl Ester

[4054] ##STR00872##

[4055] 6-Cyano-2-[1-(4-ethyl-3-iodophenyl)-1-methyl-ethyl]-benzofuran-3-carboxylic acid tert-butyl ester was converted to obtain the title compound in the same manner as the method for Compound PR6.

[4056] LCMS: m/z 558 [M+H].sup.+

Example 858

Compound FR3

6-Cyano-2-{1-[4-ethyl-3-(4-morpholin-4-yl-piperidin-1-yl)-phenyl]-1-methyl-ethyl}-benzofuran-3-carboxylic Acid Hydroiodic Acid Salt

[4057] ##STR00873##

[4058] To obtain the title compound, 6-Cyano-2-{1-[4-ethyl-3-(4-morpholin-4-yl-piperidin-1-yl)-phenyl]-1-methyl-ethyl}-benzofuran-3-carboxylic acid tert-butyl ester was deprotected by using trimethylsilyl iodide in the same manner as the method for Compound PR7.

[4059] LCMS: m/z 502 [M+H].sup.+

Example 859

Compound FR4

9-Ethyl-6,6-dimethyl-8-(4-morpholin-4-yl-piperidin-1-yl)-11-oxo-6,11-dihydro-benzo[b]naphtho[2,3-d]furan-3-carbonitrile

[4060] ##STR00874##

[4061] 6-Cyano-2-{1-[4-ethyl-3-(4-morpholin-4-yl-piperidin-1-yl)-phenyl]-1-methyl-ethyl}-benzofuran-3-carboxylic acid hydroiodic acid salt was converted in the same method as Example 805 to obtain the target compound.

[4062] LCMS: m/z 484 [M+H].sup.+

Example 860

Compound LB1

2-[4-Ethyl-3-(4-morpholin-4-yl-piperidin-1-yl)-phenyl]-2-methyl-propionic Acid

[4063] ##STR00875##

[4064] The title compound was prepared from 2-(4-ethyl-3-iodophenyl)-2-methylpropanoic acid by carrying out amination in the same manner as the method for synthesizing Compound PR6.

[4065] LCMS: m/z 361 [M+H].sup.+

Example 861

Compound LB2

2-{1-[4-Ethyl-3-(4-morpholin-4-yl-piperidin-1-yl)-phenyl]-1-methyl-ethyl}-6-iodo-1H-indole-3-carboxylic Acid Tert-Butyl Ester

[4066] ##STR00876##

[4067] 2-[4-Ethyl-3-(4-morpholin-4-yl-piperidin-1-yl)-phenyl]-2-methyl-propionic acid was converted in the same manner as the method for synthesizing Compound PR5-1 to obtain the title compound.

[4068] LCMS: m/z 658 [M+H].sup.+

[4069] HPLC retention time: 2.76 min (analysis condition U)

Example 862

Compound LB3

2-{1-[4-Ethyl-3-(4-morpholin-4-yl-piperidin-1-yl)-phenyl]-1-methyl-ethyl}-6-iodo-1H-indole-3-carboxylic Acid

[4070] ##STR00877##

[4071] 2-{1-[4-Ethyl-3-(4-morpholin-4-yl-piperidin-1-yl)-phenyl]-1-methyl-ethyl}-6-iodo-1H-indole-3-carboxylic acid tert-butyl ester was deprotected in the same manner as the method for preparing Compound PR7 to obtain the title compound.

[4072] LCMS: m/z 602 [M+H].sup.+

[4073] HPLC retention time: 2.17 min (analysis condition U)

Example 863

Compound LB4

9-Ethyl-3-iodo-6,6-dimethyl-8-(4-morpholin-4-yl-piperidin-1-yl)-5,6-dihydro-benzo[b]carbazol-11-one

[4074] ##STR00878##

[4075] 2-{1-[4-Ethyl-3-(4-morpholin-4-yl-piperidin-1-yl)-phenyl]-1-methyl-ethyl}-6-iodo-1H-indole-3-carboxylic acid was converted in the same manner as Example 805 to obtain the title compound.

[4076] LCMS: m/z 584 [M+H].sup.+

[4077] HPLC retention time: 2.25 min (analysis condition U)

[4078] The compounds described in the following Table 11 were converted and prepared from 9-ethyl-3-iodo-6,6-dimethyl-8-(4-morpholin-4-yl-piperidin-1-yl)-5,6-dihydro-benzo[b]carbazol-11-one according to the method described in the Table.

TABLE-US-00011 TABLE 11 Example Comp. HPLC Retention No. No. Structure Compound Name Condition Time m/z Method 864 LB5-1 [00879] N-[9-Ethyl-6,6- dimethyl-8-(4- morpholine-4-yl- piperidine-1-yl)-11- oxo-6,11-dihydro- 5H- benzo[b]carbazole- 3-yl]-benzamide Y 1.78 577 B2-10 865 LB5-2 [00880] 9-Ethyl-3- ethylsulfanyl-6,6- dimethyl-8-(4- morpholine-4-yl- piperidine-1-yl)-5,6- dihydro- benzo[b]carbazole- 11-one Y 2.28 518 B2-17 866 LB5-3 [00881] N-[9-Ethyl-6,6- dimethyl-8-(4- morpholine-4-yl- piperidine-1-yl)-11- oxo-6,11-dihydro- 5H- benzo[b]carbazole- 3-yl]-acetamide Y 1.50 515 B2-10

Example 867

Compound AZ1

Methanesulfonic Acid (2-fluoropyridin-4-yl)methyl Ester

[4079] ##STR00882##

[4080] (2-Fluoropyridin-4-yl) methanol (1 g) was dissolved in DCM (40 ml), added with TEA (3.3 ml) and mesyl chloride (0.67 ml), and the mixture was stirred at 0 C. for 1 hr. The mixture was concentrated and then purified by silica gel column (n-hexane/ethyl acetate=4/1) to obtain the title compound (1.18 g, 77%).

[4081] .sup.1H-NMR (270 MHz DMSO-d.sub.6) : 3.21 (3H, s), 5.38 (2H, s), 7.22 (1H, s), 7.39 (1H, d, J=5.0), 8.29 (1H, d, J=5.0)

Example 868

Compound AZ2

(2-Fluoropyridin-4-yl)acetonitrile

[4082] ##STR00883##

[4083] To the DMF (28 ml) solution of methanesulfonic acid (2-fluoropyridin-4-yl)methyl ester (1.16 g), sodium cyanide (0.42 g) was added and the mixture was stirred at 80 C. for 1 hr. The mixture was diluted with ethyl acetate (100 ml), and washed with 15% brine and distilled water in order. The organic layer was concentrated and purified by silica gel column (n-hexane/ethyl acetate=5/1) to obtain the title compound (278 mg, 36%).

[4084] .sup.1H-NMR (270 MHz DMSO-d.sub.6) : 4.22 (2H, s), 7.18 (1H, s), 7.36 (1H, d, J=5.0), 8.27 (1H, d, J=5.0)

Example 869

Compound AZ3

(2-Fluoropyridin-4-yl)2-methylpropionitrile

[4085] ##STR00884##

[4086] The title compound was prepared from (2-fluoropyridin-4-yl) acetonitrile in the same manner as the method for Compound K2.

[4087] .sup.1H-NMR (270 MHz DMSO-d.sub.6) : 1.72 (6H, s), 7.34 (1H, s), 7.53 (1H, d, J=5.3), 8.31 (1H, d, J=5.3)

Example 870

Compound AZ4

4-(2-Fluoropyridin-4-yl)-4-methyl-3-oxopentanoic Acid Ethyl Ester

[4088] ##STR00885##

[4089] The title compound was prepared from (2-fluoropyridin-4-yl) 2-methylpropionitrile in the same manner as the method for Compound K3.

[4090] .sup.1H-NMR (270 MHz DMSO-d.sub.6) : 1.13 (3H, t, J=7.3), 1.48 (6H, s), 3.57 (2H, s), 4.01 (2H, q, J=7.3), 7.12 (1H, s), 7.25 (1H, d, J=5.3), 8.22 (1H, d, J=5.3)

Example 871

Compound AZ5

6-Cyano-2-[1-(2-fluoropyridin-4-yl)-1-methyl-ethyl]-1H-indole-3-carboxylic Acid Ethyl Ester

[4091] ##STR00886##

[4092] The title compound was prepared from 4-(2-fluoropyridin-4-yl)-4-methyl-3-oxopentanoic acid ethyl ester in the same manner as the method for Compound K4 and Compound K5.

[4093] LCMS: m/z 352 [M+H].sup.+

[4094] .sup.1H-NMR (270 MHz DMSO-d.sub.6) : 1.05 (3H, t, J=7.3), 1.82 (6H, s), 3.98 (2H, q, J=7.3), 6.99-7.02 (2H, m), 7.16 (1H, dd, J=8.4, 1.5), 7.97 (1H, s), 8.05-8.11 (2H, m)

Example 872

Compound AZ6

6-Cyano-2-[1-(2-(4-morpholin-4-yl-piperidin-1-yl))pyridin-4-yl)-1-methyl-ethyl]-1H-indole-3-carboxylic Acid Ethyl Ester

[4095] ##STR00887##

[4096] 6-Cyano-2-[1-(2-fluoropyridin-4-yl)-1-methyl-ethyl]-1H-indole-3-carboxylic acid ethyl ester (110 mg) was dissolved in NMP (3.3 ml), added with 4-morpholin-4-yl-piperidine (319 mg), and stirred in a sealing tube at 120 C. for 1 hr. The reaction mixture was diluted with ethyl acetate (50 ml) and washed with 15% brine and distilled water in order. The organic layer was concentrated and purified by silica gel column (DCM/methanol=20/1) to obtain the title compound (120 mg, 76%).

[4097] LCMS: m/z 502 [M+H].sup.+

Example 873

Compound AZ7-1

5,5-Dimethyl-3-(4-morpholin-4-yl-piperidin-1-yl)-11-oxo-6,11-dihydro-5H-pyrido[4,3-b] carbazole-8-carboxylic Acid Amide

[4098] ##STR00888##

[4099] 6-Cyano-2-[1-(2-(4-morpholin-4-yl-piperidin-1-yl))pyridin-4-yl)-1-methyl-ethyl]-1H-indole-3-carboxylic acid ethyl ester (110 mg) was dissolved in Eaton's reagent (2.5 ml) and stirred at 55 C. for 17 hrs. The reaction mixture was neutralized with saturated aqueous solution of sodium bicarbonate. The precipitated matters were collected by filtration, and then washed with water to obtain the title compound (72 mg, 70%).

[4100] LCMS: m/z 474 [M+H].sup.+

[4101] HPLC retention time: 1.17 min (analysis condition U)

[4102] .sup.1H-NMR (270 MHz DMSO-d.sub.6) : 1.38 (2H, m), 1.75 (6H, s), 1.88 (2H, m), 2.44 (5H, m), 2.94 (2H, m), 3.57 (4H, m), 4.58 (2H, m), 7.10 (1H, s), 7.32 (1H, s), 7.75 (1 H, d, J=8.4), 8.00 (2H, m), 8.15 (1H, d, J=8.4), 8.85 (1H, s), 12.3 (1H, s)

Example 874

Compound AZ7-2

5,5-Dimethyl-3-(4-morpholin-4-yl-piperidin-1-yl)-11-oxo-6,11-dihydro-5H-pyrido[4,3-b] carbazole-8-carbonitrile

[4103] ##STR00889##

[4104] 5,5-Dimethyl-3-(4-morpholin-4-yl-piperidin-1-yl)-11-oxo-6,11-dihydro-5H-pyrido[4,3-b]carbazole-8-carboxylic acid amide (54 mg) was dissolved in DMF (1 ml), added with thionyl chloride (25 L), and the mixture was stirred at room temperature for 1 hr. The reaction mixture was diluted with water. The precipitated matters were collected by filtration to obtain the title compound (25 mg, 49%).

[4105] LCMS: m/z 456 [M+H].sup.+

[4106] HPLC retention time: 1.55 min (analysis condition U) .sup.1H-NMR (270 MHz DMSO-d.sub.6) : 1.36 (2H, m), 1.76 (6H, s), 1.89 (2H, m), 2.44 (5H, m), 2.95 (2H, m), 3.57 (4H, m) 4.58 (2H, m), 7.10 (1H, s), 7.59 (1H, d, J=8.0), 7.99 (1H, s), 8.29 (1H, d, J=8.0), 8.86 (1H, s), 12.7 (1H, s)

[4107] The compounds described in the following Tables 12-13 were synthesized by introducing a corresponding amino group to 6-cyano-2-[1-(2-fluoropyridin-4-yl)-1-methyl-ethyl]-1H-indole-3-carboxylic acid ethyl ester and forming a ring according to the method that is used for the synthesis of Compound AZ7-1. Furthermore, the preparation was carried out by converting the substituent group at position 3 from a carboxamide group to a cyano group according to the method that is used for the synthesis of Compound AZ7-2.

TABLE-US-00012 TABLE 12 HPLC Reten- Example Comp. Con- tion No. No. Structure Compound Name dition Time m/z 875 AZ7-3 [00890] 3-[4-((2R,6S)-2,6- Dimethyl-morpholine- 4-yl)-piperidine-1- yl]-5,5-dimethyl-11- oxo-6,11-dihydro-5H- pyrido[4,3- b]carbazole-8- carboxylic acid amide U 1.32 502 876 AZ7-4 [00891] 3-[4-((2R,6S)-2,6- Dimethyl-morpholine- 4-yl)-piperidine-1- yl]-5,5-dimethyl-11- oxo-6,11-dihydro-5H- pyrido[4,3- b]carbazole-8- carbonitrile U 1.70 484 877 AZ7-5 [00892] 3-[1,4]Bipiperidinyl- 1-yl-5,5-dimethyl- 11-oxo-6,11-dihydro- 5H-pyrido[4,3- b]carbazole-8- carboxylic acid amide U 1.30 472 878 AZ7-6 [00893] 5,5-Dimethyl-3-(4- methyl-4-morpholine- 4-yl-piperidine-1-yl)- 11-oxo-6,11-dihydro- 5H-pyrido[4,3- b]carbazole-8- carboxylic acid amide Y 1.00 488 879 AZ7-7 [00894] 5,5-Dimethyl-3-(4- methyl-4-morpholine- yl-piperidine-1-yl)- 11-oxo-6,11-dihydro- 5H-pyrido[4,3- b]carbazole-8- carbonitrile Y 1.62 470 880 AZ7-8 [00895] 3-(4-Cyclobutyl- piperazine-1-yl)-5,5- dimethyl-11-oxo- 6,11-dihydro-5H- pyrido[4,3- b]carbazole-8- carboxylic acid amide Y 1.22 444 881 AZ7-9 [00896] 3-(4-Cyclobutyl- piperazine-1-y)-5,5- dimethyl-11-oxo- 6,11-dihydro-5H- pyrido[4,3- b]carbazole-8- carbonitrile Y 1.55 426 882 AZ7-10 [00897] 3-[1,4]Bipiperidinyl- 1-yl-5,5-dimethyl- 11-oxo-6,11-dihydro- 5H-pyrido[4,3- b]carbazole-8- carbonitrile Y 1.73 454 883 AZ7-11 [00898] 5.5-Dimethyl-3- morpholine-4-yl-11- oxo-6,11-dihydro-5H- pyrido[4,3- b]carbazole-8- carboxylic acid amide U 1.33 391 884 AZ7-12 [00899] 5,5-Dimethyl-3- morpholine-4-yl-11- oxo-6,11-dihydro-5H- pyrido[4,3- b]carbazole-8- carbonitrile U 1.77 373 885 AZ7-13 [00900] 3-[4-(1-Ethyl- cyclobutyl)- piperazine-1-yl]-5,5- dimethyl-11-oxo- 6,11-dihydro-5H- pyrido[4,3- b]carbazole-8- carbonitrile Y 1.93 464 886 AZ7-14 [00901] 3-(4-Ethyl-4- morpholine-4-yl- piperidine-1-yl)-5,5- dimethyl-11-oxo- 6,11-dihydro-5H- pyrido[4,3- b]carbazole-8- carboxylic acid amide Y 1.18 502 887 AZ7-15 [00902] 3-(4-Ethyl-4- morpholine-4-yl- piperidine-1-yl)-5,5- dimethyl-11-oxo- 6,11-dihydro-5H- pyrido[4,3- b]carbazole-8- carbonitrile Y 1.78 484 888 AZ7-16 [00903] 3-[4-(1-Ethyl- cyclobutyl)- piperazine-1-yl]-5,5- dimetbyl-11-oxo- 6,11-dihydro-5H- pyrido[4,3- b]carbazole-8- carboxylic acid amide Y 1.25 472

TABLE-US-00013 TABLE 13 HPLC Reten- Example Comp. Con- tion No. No. Structure Compound Name dition Time m/z 889 AZ7-17 [00904] 3-(4-Isopropyl- 4-morpholine-4- yl-piperidine-1- yl)-5,5-dimethyl- 11-oxo-6,11- dihydro-5H- pyrido[4,3- b]carbazole-8- carboxylic acid amide U 1.27 516 890 AZ7-18 [00905] 5,5-Dimethyl-3- (4-morpholine-4- yl-4-propyl- piperidine-1-yl)- 11-oxo-6,11- dihydro-5H- pyrido[4.3- b]carbazole-8- carboxylic acid amide U 1.36 516 891 AZ7-19 [00906] 5,5-Dimethyl-3- (4-morpholine-4- yl-4-propyl- piperidine-1-yl)- 11-oxo-6,11- dihydro-5H- pyrido[4,3- b]carbazole-8- carbonitrile U 1.68 498 892 AZ7-20 [00907] 3-(4-isopropyl- 4-morpholine-4- yl-piperidine-1- yl)-5,5-dimethyl- 11-oxo-6,11- dihydro-5H- pyrido[4,3- b]carbazole-8- carbonitrile U 1.60 498 893 AZ7-21 [00908] 5,5-Dimethyl- 11-oxo-3-[4-(1- propyl- cyclobutyl)- piperazine-1-yl]- 6,11-dihydro-5H- pyrido[4,3- b]carbazole-8- carboxylic acid amide U 1.58 486 894 AZ7-22 [00909] 5,5-Dimethyl- 11-oxo-3-[4-(1- propyl- cyclobutyl)- piperazine-1-yl]- 6,11-dihydro-5H- pyrido[4,3- b]carbazole-8- carbonitrile U 1.97 468

[4108] The compounds described in the following Table 14 were synthesized from (2-chloro-3-fluoropyridin-4-yl)methanol according to the method that is used for the synthesis of Compound AZ1 to AZ7-2.

TABLE-US-00014 TABLE 14 HPLC Reten- Example Comp. Con- tion No. No. Structure Compound Name dition Time m/z 895 AZ7-23 [00910] 4-Fluoro-5,5- dimethyl-3-(4- morpholine-4-yl- piperidine-1-yl)-11- oxo-6,11-dihydro- 5H-pyrido[4,3- b]carbazole-8- carboxylic acid amide U 1.37 492 896 AZ7-24 [00911] 4-Fluoro-5,5- dimethyl-3-(4- morpholin-4-yl- piperidin-1-yl)-11- oxo-6,11-dihydro- 5H-pyrido[4,3- b]carbazole-8- carbonitrile U 1.74 474 897 AZ7-25 [00912] 4-Fluoro-5,5- dimethyl-11-oxo-3- [4-(3-oxo- piperazin-1-yl)- piperidin-1-yl]-6,11- dihydro-5H- pyrido[4,3- b]carbazole-8- carboxylic acid amide U 1.32 505 898 AZ7-26 [00913] 3- [1,4]Bipiperidinyl- 1-yl-4-fluoro-5,5- dimethyl-11-oxo- 6,11-dihydro-5H- pyrido[4,3- b]carbazole-8- carboxylic acid amide U 1.45 490 899 AZ7-27 [00914] 3- [1,4]Bipiperidinyl- 1-yl-4-fluoro-5,5- dimethyl-11-oxo- 6,11-dihydro-5H- pyrido[4,3- b]carbazole-8- carbonitrile U 1.87 472

Example 900

Compound BZ1

2-Cyano-4-hydrazinopyridine

[4109] ##STR00915##

[4110] 4-Chloro-2-cyanopyridine (1 g) was dissolved in hydrazine monohydrate (1 ml) and 1,4-dioxane (10 ml), and stirred overnight under reflux. The reaction solution was diluted with water (30 ml) and extracted repeatedly with ethyl acetate. The organic layer was concentrated to obtain the title compound as a crude product, which was used for the next step without further purification.

[4111] LCMS: m/z 135 [M+H].sup.+

Example 901

Compound BZ2-1

8-Methoxy-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[f]pyrido[4,3-b]indol-3-carbonitrile

[4112] ##STR00916##

[4113] According to the method used for synthesizing Compound A3-1, the intermediate was prepared from 2-cyano-4-hydrazinopyridine and 7-methoxy-1,1-dimethyl-3,4 dihydro-1H-naphthalen-2-one. Without any purification, the intermediate was subjected to oxidation according to the method used for synthesizing Compound A4 to obtain the title compound.

[4114] LCMS: m/z 318 [M+H].sup.+

[4115] HPLC retention time: 2.10 min (analysis condition U)

Example 902

Compound BZ2-2

3-Chloro-8-methoxy-6,6-dimethyl-5,6-dihydro-benzo[f]pyrido[4,3-b]indol-11-one

[4116] ##STR00917##

[4117] According to the method used for synthesizing Compound A3-1, the intermediate was prepared from 2-chloro-4-hydrazinopyridine and 7-methoxy-1,1-dimethyl-3,4 dihydro-1H-naphthalen-2-one. Without any purification, the intermediate was subjected to oxidation according to the method used for synthesizing Compound A4 to obtain the title compound.

[4118] LCMS: m/z 327, 329 [M+H].sup.+

[4119] HPLC retention time: 1.80 min (analysis condition S)

Example 903

Compound CZ1

2-Bromo-8-methoxy-10,10-dimethyl-10,11-dihydro-1,11-diaza-benzo[b]fluoren-5-one

[4120] ##STR00918##

[4121] According to the method used for synthesizing Compound A3-1, the intermediate was prepared from 2-bromo-6-hydrazinopyridine and 7-methoxy-1,1-dimethyl-3,4 dihydro-1H-naphthalen-2-one. Without any purification, the intermediate was subjected to oxidation according to the method used for synthesizing Compound A4 to obtain the title compound.

[4122] LCMS: m/z 371, 373 [M+H].sup.+

[4123] HPLC retention time: 2.85 min (analysis condition U)

Example 904

Compound CZ2

8-Methoxy-10,10-dimethyl-5-oxo-10,11-dihydro-5H-1,11-diaza-benzo[b]fluorene-2-carbonitrile

[4124] ##STR00919##

[4125] According to the method 1 for Compound A5-2, 2-bromo-8-methoxy-10,10-dimethyl-10,11-dihydro-1,11-diaza-benzo[b]fluoren-5-one was subjected to cyanation to obtain the title compound.

[4126] LCMS: m/z 318 [M+H].sup.+

[4127] HPLC retention time: 2.35 min (analysis condition U)

Example 905

Compound CZ3

8-Hydroxy-10,10-dimethyl-5-oxo-10,11-dihydro-5H-1,11-diaza-benzo[b]fluorene-2-carbonitrile

[4128] ##STR00920##

[4129] According to the method used for synthesizing Compound A6, 8-methoxy-10,10-dimethyl-5-oxo-10,11-dihydro-5H-1,11-diaza-benzo[b]fluorene-2-carbonitrile was subjected to demethylation to obtain the title compound.

[4130] LCMS: m/z 304 [M+H].sup.+

[4131] HPLC retention time: 1.72 min (analysis condition S)

Example 906

Compound CZ4

Trifuloromethanesulfonic Acid 2-cyano-10,10-dimethyl-5-oxo-10,11-dihydro-5H-1,11-diaza-benzo[b]fluoren-8-yl Ester

[4132] ##STR00921##

[4133] According to the method used for synthesizing Compound B1, 8-hydroxy-10,10-dimethyl-5-oxo-10,11-dihydro-5H-1,11-diaza-benzo[b]fluorene-2-carbonitrile was subjected to trifluoromethanesulfone esterification to obtain the title compound.

[4134] LCMS: m/z 436 [M+H].sup.+

[4135] HPLC retention time: 3.32 min (analysis condition Y)

Example 907

Compound CZ5-1

10,10-Dimethyl-5-oxo-8-piperazin-1-yl-10,11-dihydro-5H-1,11-diaza-benzo[b]fluorene-2-carbonitrile

[4136] ##STR00922##

[4137] According to the method used for synthesizing Compound B2-1, trifluoromethanesulfonic acid 2-cyano-10,10-dimethyl-5-oxo-10,11-dihydro-5H-1,11-diaza-benzo[b]fluoren-8-yl ester was introduced with piperazine to obtain the title compound.

[4138] LCMS: m/z 372 [M+H].sup.+

[4139] HPLC retention time: 1.17 min (analysis condition S)

Example 908

Compound CZ5-2

10,10-Dimethyl-8-(4-morpholin-4-yl-piperidin-1-yl)-5-oxo-10,11-dihydro-5H-1,11-diaza-benzo[b]fluorene-2-carbonitrile

[4140] ##STR00923##

[4141] According to the method used for synthesizing Compound B2-1, trifluoromethanesulfonic acid 2-cyano-10,10-dimethyl-5-oxo-10,11-dihydro-5H-1,11-diaza-benzo[b]fluoren-8-yl ester was introduced with 4-morpholin-4-yl piperidine to obtain the title compound.

[4142] LCMS: m/z 456 [M+H].sup.+

[4143] HPLC retention time: 1.68 min (analysis condition U)

Example 909

Compound CZ6

8-(4-Cyclobutyl-piperazin-1-yl)-10,10-dimethyl-5-oxo-10,11-dihydro-5H-1,11-diaza-benzo[b]fluorene-2-carbonitrile

[4144] ##STR00924##

[4145] According to the method used for synthesizing Compound B3-32, 10,10-dimethyl-5-oxo-8-piperazin-1-yl-10,11-dihydro-5H-1,11-diaza-benzo[b]fluorene-2-carbonitrile was subjected to reductive amination with cyclobutanone to obtain the title compound.

[4146] LCMS: m/z 426 [M+H].sup.+

[4147] HPLC retention time: 1.60 min (analysis condition U)

Example 910

Compound DZ1

6-Ethynyl-7-methoxy-1,1-dimethyl-3,4-dihydro-1H-naphthalen-2-one

[4148] ##STR00925##

[4149] 6-Bromo-7-methoxy-1,1-dimethyl-3,4-dihydro-1H-naphthalen-2-one (1 g) was dissolved in acetonitrile (50 ml), added with PdCl.sub.2(CH.sub.3CN).sub.2 (45 mg), X-phos (168 mg), CsCO.sub.3 (1.2 g) and trimethylsilylacetylene (0.9 ml), and the mixture was stirred at 85 C. for 2 hrs. The reaction mixture was diluted with ethyl acetate (100 ml). The organic layer was washed twice with 10% brine and concentrated under reduced pressure. The resulting residues were dissolved in THF (10 ml), added with the THF solution (4 ml) comprising tetrabutylammonium fluoride and stirred at room temperature for 1 hr. The reaction mixture was diluted with ethyl acetate (100 ml). The organic layer was washed twice with 10% brine and concentrated under reduced pressure. The resulting residues were purified by silica gel column (n-hexane/ethyl acetate=9/1) to obtain the title compound (346 mg, two step yield 43%).

[4150] LCMS: m/z 229 [M+H].sup.+

Example 911

Compound DZ2

6-Ethyl-7-methoxy-1,1-dimethyl-3,4-dihydro-1H-naphthalen-2-one

[4151] ##STR00926##

[4152] 6-Ethynyl-7-methoxy-1,1-dimethyl-3,4-dihydro-1H-naphthalen-2-one (346 mg) was dissolved in ethanol:THF (=2:1 mixture solvent, 20 ml), added with 10% Pd/C (170 mg), and then the mixture was stirred at room temperature for 1 hr under hydrogen atmosphere. The catalyst was removed by filtration and the organic layer was concentrated under reduced pressure to obtain the title compound (322 mg, yield 91%).

[4153] LCMS: m/z 233 [M+H].sup.+

Example 912

Compound DZ3

2-Bromo-7-ethyl-8-methoxy-10,10-dimethyl-10,11-dihydro-1,11-diaza-benzo[b]fluoren-5-one

[4154] ##STR00927##

[4155] According to the method used for synthesizing Compound A3-1, the intermediate was prepared from 2-bromo-6-hydrazinopyridine and 6-ethyl-7-methoxy-1,1-dimethyl-3,4-dihydro-1H-naphthalen-2-one. Without any purification, the intermediate was subjected to oxidation according to the method used for synthesizing Compound A4 to obtain the title compound.

[4156] LCMS: m/z 399, 401 [M+H].sup.+

[4157] HPLC retention time: 3.35 min (analysis condition Y)

Example 913

Compound DZ4

7-Ethyl-8-methoxy-10,10-dimethyl-5-oxo-10,11-dihydro-5H-1,11-diaza-benzo[b]fluorene-2-carbonitrile

[4158] ##STR00928##

[4159] According to the method 1 for Compound A5-2, 2-bromo-7-ethyl-8-methoxy-10,10-dimethyl-10,11-dihydro-1,11-diaza-benzo[b]fluoren-5-one was subjected to cyanation to obtain the title compound.

[4160] LCMS: m/z 346 [M+H].sup.+

[4161] HPLC retention time: 3.05 min (analysis condition Y)

Example 914

Compound DZ5

7-Ethyl-8-hydroxy-10,10-dimethyl-5-oxo-10,11-dihydro-5H-1,11-diaza-benzo[b]fluorene-2-carbonitrile

[4162] ##STR00929##

[4163] According to the method used for synthesizing Compound A5, 7-ethyl-8-methoxy-10,10-dimethyl-5-oxo-10,11-dihydro-5H-1,11-diaza-benzo[b]fluorene-2-carbonitrile was subjected to demethylation to obtain the title compound.

[4164] LCMS: m/z 332 [M+H].sup.+

[4165] HPLC retention time: 2.60 min (analysis condition Y)

Example 915

Compound DZ6-1

Trifuloro-Methanesulfonic Acid 2-cyano-7-ethyl-10,10-dimethyl-5-oxo-10,11-dihydro-5H-1,11-diaza-benzo[b]fluoren-8-yl Ester

[4166] ##STR00930##

[4167] According to the method used for synthesizing Compound B1, 7-ethyl-8-hydroxy-10,10-dimethyl-5-oxo-10,11-dihydro-5H-1,11-diaza-benzo[b]fluorene-2-carbonitrile was subjected to trifluoromethanesulfone esterification to obtain the title compound.

[4168] LCMS: m/z 464 [M+H].sup.+

[4169] HPLC retention time: 3.50 min (analysis condition Y)

[4170] The compounds described in the following Table 15 were prepared from trifluoro-methanesulfonic acid 2-cyano-7-ethyl-10,10-dimethyl-5-oxo-10,11-dihydro-5H-1,11-diaza-benzo[b]fluoren-8-yl ester and corresponding amine according to the method that is used for the synthesis of Compound B2-10. The compounds of Example 919 and Example 920 were obtained as a by-product of the reaction.

TABLE-US-00015 TABLE 15 HPLC Reten- Example Comp. Con- tion No. No. Structure Compound Name dition Time m/z 916 DZ7-1 [00931] 6-(4-Cyclobutyl- piperazine-1-yl)-7-ethyl- 10,10-dimethyl-5-oxo- 10,11-dihydro-5H-1,11- diaza-benzo[b]fluorene- 2-carbonitrile Y 1.83 454 917 DZ7-2 [00932] 7-Ethyl-10,10-dimethyl- 8-(4-morpholine-4-yl- piperidine-1-yl)-5-oxo- 10,11-dihydro-5H-1,11- diaza-benzo[b]fluorene- 2-carbontrile Y 1.85 484 918 DZ7-3 [00933] 7-Ethyl-10,10-dimethyl- 8-morpholine-4-yl-5- oxo-10,11-dihydro-5H- 1,11-diaza- benzo[b]fluorene-2- carbonitrile Y 3.0.2 401 919 DZ7-4 [00934] 7-Ethy-10,10-dimethyl- 5-oxo-10,11-dihydro-5H- 1,11-diaza- benzo[b]fluorene-2- carbonitrile Y 3.07 316 920 DZ7-5 [00935] 7-Ethy-10,10-dimethyl- 2-(morpholine-4- carbonyl)-8-morpholine- 4-yl-10,11-dihydro-1,11- diaza-benzo[b]fluorene- 5-one Y 2.70 489

Example 921

Compound DZ6-2

8-(2-Diethylamino-ethoxy)-11-(2-diethylamino-ethyl)-7-ethyl-10,10-dimethyl-5-oxo-10,11-dihydro-5H-1,11-diaza-benzo[b]fluorene-2-carbonitrile

[4171] ##STR00936##

[4172] According to the method used for synthesizing Compound A7-17, 7-ethyl-8-hydroxy-10,10-dimethyl-5-oxo-10,11-dihydro-5H-1,11-diaza-benzo[b]fluorene-2-carbonitrile was alkylated to obtain the title compound.

[4173] LCMS: m/z 530 [M+H].sup.+

[4174] HPLC retention time: 1.38 min (analysis condition Y)

Example 922

Compound EZ1

2-(6-Methoxy-pyridin-2-yl)-2-methyl-propionic Acid Ethyl Ester

[4175] ##STR00937##

[4176] 2-Bromo-6-methoxypyridine (7.0 g), ethyl isobutyrate (4.75 g), tri t-butylphosphine (300 mg) and Pd.sub.2(dba).sub.3 (680 mg) were dissolved in toluene (200 ml) under nitrogen atmosphere, added with THF solution of LiHMDS (1.6 M, 24 ml), and the mixture was stirred at 100 C. for 6 hrs. The reaction mixture was diluted with ethyl acetate (300 ml), and washed three times with 15% brine (200 ml). The organic layer was concentrated under reduced pressure and the resulting residues were purified by silica gel column (n-hexane/ethyl acetate=4/1) to obtain the title compound (5.353 g, yield 60%).

[4177] LCMS: m/z 224 [M+H].sup.+

Example 923

Compound EZ2

2-(6-Methoxy-pyridin-2-yl)-2-methyl-propionic Acid

[4178] ##STR00938##

[4179] 2-(6-Methoxy-pyridin-2-yl)-2-methyl-propionic acid ethyl ester (5.33 g) was dissolved in methanol (200 ml), added with 5 N aqueous solution of potassium hydroxide (25 ml), and then stirred under reflux. The reaction mixture was concentrated and neutralized with 2 N hydrochloric acid. The precipitated matters were collected by filtration and dried to obtain the title compound (3.55 g).

[4180] LCMS: m/z 196 [M+H].sup.+

Example 924

Compound EZ3

4-(6-Methoxy-pyridin-2-yl)-4-methyl-3-oxo-pentanoic acid tert-butyl ester

[4181] ##STR00939##

[4182] The title compound was synthesized from 2-(6-methoxy-pyridin-2-yl)-2-methyl-propionic acid and mono-tert-butyl malonic acid according to the method used for the synthesis of Compound PR4. The resultant was used for the next step without further purification.

Example 925

Compound EZ4-1

6-Cyano-2-[1-(6-methoxy-pyridin-2-yl)-1-methyl-ethyl]-1H-indole-3-carboxylic Acid Tert-Butyl Ester

[4183] ##STR00940##

[4184] According to the method that is used for the preparation of Compound PR5-1, the title compound was synthesized from 4-(6-methoxy-pyridin-2-yl)-4-methyl-3-oxo-pentanoic acid tert-butyl ester and 4-chloro-3-nitrobenzonitrile

[4185] LCMS: m/z 392 [M+H].sup.+

Example 926

Compound EZ4-2

6-Cyano-2-[1-(6-methoxy-pyridin-2-yl)-1-methyl-ethyl]-benzofuran-3-carboxylic Acid Tert-Butyl Ester

[4186] ##STR00941##

[4187] According to the method that is used for the preparation of Compound FR1, the title compound was synthesized from 4-(6-methoxy-pyridin-2-yl)-4-methyl-3-oxo-pentanoic acid tert-butyl ester and 4-chloro-3-nitrobenzonitrile.

[4188] LCMS: m/z 393 [M+H].sup.+

Example 927

Compound EZ5-1

6-Cyano-2-[1-(6-methoxy-pyridin-2-yl)-1-methyl-ethyl]-1H-indole-3-carboxylic Acid

[4189] ##STR00942##

[4190] According to the method that is used for the preparation of Compound PR7, the title compound was synthesized from 6-cyano-2-[1-(6-methoxy-pyridin-2-yl)-1-methyl-ethyl]-1H-indole-3-carboxylic acid tert-butyl ester.

[4191] LCMS: m/z 336 [M+H].sup.+

Example 928

Compound EZ5-2

6-Cyano-2-[1-(6-methoxy-pyridin-2-yl)-1-methyl-ethyl]-benzofuran-3-carboxylic acid

[4192] ##STR00943##

[4193] According to the method that is used for the preparation of Compound PR7, the title compound was synthesized from 6-cyano-2-[1-(6-methoxy-pyridin-2-yl)-1-methyl-ethyl]-benzofuran-3-carboxylic acid tert-butyl ester.

[4194] LCMS: m/z 337 [M+H].sup.+

Example 929

Compound EZ6-1

2-Methoxy-11,11-dimethyl-5-oxo-10,11-dihydro-5H-pyrido[2,3-b] carbazole-8-carboxylic Acid Amide

[4195] ##STR00944##

[4196] According to the method that is used for the preparation of Compound AZ7-1, the title compound was synthesized from 6-cyano-2-[1-(6-methoxy-pyridin-2-yl)-1-methyl-ethyl]-1H-indole-3-carboxylic acid.

[4197] LCMS: m/z 336 [M+H].sup.+

[4198] HPLC retention time: 1.98 min (analysis condition S)

Example 930

Compound EZ6-2

2-Methoxy-11,11-dimethyl-5-oxo-5,11-dihydro-benzo[4,5] furo[3,2-g] quinoline-8-carboxylic Acid Amide

[4199] ##STR00945##

[4200] According to the method that is used for the preparation of Compound AZ7-1, the title compound was synthesized from 6-cyano-2-[1-(6-methoxy-pyridin-2-yl)-1-methyl-ethyl]-benzofuran-3-carboxylic acid.

[4201] LCMS: m/z 337 [M+H].sup.+

[4202] HPLC retention time: 2.38 min (analysis condition S)

Example 931

Compound EZ7-1

2-Methoxy-11,11-dimethyl-5-oxo-10,11-dihydro-5H-pyrido[2,3-b] carbazole-8-carbonitrile

[4203] ##STR00946##

[4204] According to the method that is used for the preparation of Compound AZ7-2, the title compound was synthesized from 2-methoxy-11,11-dimethyl-5-oxo-10,11-dihydro-5H-pyrido[2,3-b]carbazole-8-carboxylic acid amide.

[4205] LCMS: m/z 318 [M+H].sup.+

[4206] HPLC retention time: 2.60 min (analysis condition S)

Example 932

Compound EZ7-2

2-Methoxy-11,11-dimethyl-5-oxo-5,11-dihydro-benzo[4,5] furo[3,2-g] quinoline-8-carbonitrile

[4207] ##STR00947##

[4208] According to the method that is used for the preparation of Compound AZ7-2, the title compound was synthesized from 2-methoxy-11,11-dimethyl-5-oxo-5,11-dihydro-benzo[4,5]furo[3,2-g]quinoline-8-carboxylic acid amide.

[4209] LCMS: m/z 319 [M+H].sup.+

[4210] HPLC retention time: 3.18 min (analysis condition S)

Example 933

Compound EZ8-1

2-Hydroxy-11,11-dimethyl-5-oxo-10,11-dihydro-5H-pyrido[2,3-b] carbazole-8-carbonitrile

[4211] ##STR00948##

[4212] According to the method that is used for the preparation of Compound A5, 2-methoxy-11,11-dimethyl-5-oxo-10,11-dihydro-5H-pyrido[2,3-b] carbazole-8-carbonitrile was demethylated to synthesize the title compound.

[4213] LCMS: m/z 304 [M+H].sup.+

[4214] HPLC retention time: 1.70 min (analysis condition U)

Example 934

Compound EZ8-2

2-Hydroxy-11,11-dimethyl-5-oxo-5,11-dihydro-benzo[4,5]furo[3,2-g]quinoline-8-carbonitrile

[4215] ##STR00949##

[4216] According to the method that is used for the preparation of Compound A5, 2-methoxy-11,11-dimethyl-5-oxo-5,11-dihydro-benzo[4,5]furo[3,2-g] quinoline-8-carbonitrile was demethylated to synthesize the title compound.

[4217] LCMS: m/z 305 [M+H].sup.+

[4218] HPLC retention time: 2.17 min (analysis condition U)

[4219] The compounds described in the following Table 16 were synthesized from 2-hydroxy-11,11-dimethyl-5-oxo-10,11-dihydro-5H-pyrido[2,3-b] carbazole-8-carbonitrile or from 2-hydroxy-11,11-dimethyl-5-oxo-5,11-dihydro-benzo[4,5]furo[3,2-g]quinoline-8-carbonitrile according to the method described in the Table.

TABLE-US-00016 TABLE 16 HPLC Reten- Example Comp. Con- tion No. No. Structure Compound Name dition Time m/z Method 935 EZ9-1 [00950] Trifluoro- methanesulfonic acid 8-cyano- 11,11-dimethyl-5- oxo-10,11- dihydro-5H- pyrido[2,3- b]carbazol-2-yl ester U 2.93 436 B1 936 EZ9-2 [00951] 11,11-Dimethyl- 5-oxo-2- (tetrahydro-pyran- 4-yloxy)-10,11- dihydro-5H- pyrido[2,3- b]carbazole-8- carbonitrile U 2.57 388 A7-1 937 EZ9-3 [00952] 2-(2- Diethylamino- ethoxy)-11,11- dimethyl-5-oxo- 10,11-dihydro-5H- pyrido[2,3- b]carbazole-8- carbonitrile Y 1.63 403 A7-17 938 EZ9-4 [00953] 2-(2- Diethylamino- ethoxy)-10-(2- diethylamino- ethyl)-11,11- dimethyl-5-oxo- 10,11-dihydro-5H- pyrido[2,3- b]carbazole-8- carbonitrile Y 1.82 502 A7-17 939 EZ9-5 [00954] 2-(2- Diethylamino- ethoxy)-11,11- dimethyl-5-oxo- 5,11-dihydro- benzo[4,5]furo[3,2- g]quinoline-8- carbonitrile Y 1.77 404 A7-17

[4220] The compounds described in the following Table 17 were synthesized from Compound W3 and corresponding halide by alkylation of hydroxyl group according to the method that is used for the synthesis of Compound A7-17.

TABLE-US-00017 TABLE 17 Example Comp. HPLC Retention No. No. Structure Compound Name Condition Time m/z 940 W4-3 [00955] 7-(2-Dimethylamino- ethoxy)-6,6-dimethyl- 11-oxo-6,11-dihydro- 5H-benzo[b]carbazole- 3-carbonitrile I 0.96 374.0 941 W4-4 [00956] 7-(3-Dimethylamino- propoxy)-6,6-dimethyl- 11-oxo-6,11-dihydro- 5H-benzo[b]carbazole- 3-carbonitrile I 0.92 338.0

[4221] The compounds described in the following Table 18 were synthesized according to the method shown below. Specifically, Compound GT1-1 was prepared from Compound J2 and phenylhydrazine according to the method that is used for the synthesis of Compound A3 and Compound A4. Subsequently, in accordance with the methylation carried out in the same manner as Compound A10-1, Compound GT1-2 was prepared.

TABLE-US-00018 TABLE 18 Example Comp. HPLC Retention No. No. Structure Compound Name Condition Time m/z Method 942 GT1-1 [00957] 9-Methoxy-6,6- dimethyl-5,6- dihydro- benzo[b]carbazol- 11-one A 2.36 292.0 A3 A4 943 GT1-2 [00958] 9-Methoxy-5,6,6- trimethyl-5,6- dihydro- benzo[b]carbazol- 11-one A 2.53 306.0 A10-1

[4222] The compounds described in the following Table 19 were synthesized according to the method shown below. Specifically, Compound GT2-1 was prepared from Compound A2 and phenylhydrazine according to the method that is used for the synthesis of Compound A3 and Compound A4.

[4223] Subsequently, by carrying out the alkylation in the same manner as Compound A10-1, Compound GT2-2 and Compound GT2-8 were prepared.

[4224] To obtain the compounds of the Table, chemical conversion of Compound GT2-1 or the 5-alkylate of Compound GT2-1 was achieved by using in combination the functional group modifications (e.g., demethylation according to the method used for the preparation of Compound A6 and subsequent introduction of a functional group, etc.) as explained before and described in the Table.

TABLE-US-00019 TABLE 19 Exam- HPLC Reten- ple Comp. Condi- tion No. No. Structure Compound Name tion Time m/z Method 944 GT2-1 [00959] 8-Methoxy-6,6- dimethyl-5,6- dihydro- benzo[b]carbazol- 11-one A 2.30 292.0 A3 A4 945 GT2-2 [00960] 8-Methoxy-5,6,6- trimethyl-5,6 dihydro- benzo[b]carbazol- 11-one A 2.55 306.0 A10-1 946 GT2-3 [00961] 8-(2- Diethylamino- ethoxy)-5,6,6- trimethyl-5,6- dihydro- benzo[b]carbazol- 11-one A 1.90 391.0 A6 A7-17 A10-1 947 GT2-4 [00962] 8-((R)-2,3- Dihydroxy- propoxy)-5,6,6- trimethyl-5,6- dihydro- benzo[b]carbazol- 11-one A 1.90 366.0 A6 A7-17 A10-1 948 GT2-5 [00963] 8-(2- Diethylamino- ethoxy)-6,6- dimethyl-5,6- dihydro- benzo[b]carbazol- 11-one F 1.93 377.3 A6 A7-17 949 GT2-6 [00964] 8-(2- Diethylamino- ethoxy)-6,6- dimethyl-5- propyl-5,6- dihydro- benzo[b]carbazol- 11-one A 2.09 419.0 A6 A7-17 A10-1 950 GT2-7 [00965] 5-Benzyl-8-(2- diethylamino- ethoxy)-(6,6- dimethyl-5,6- dihydro- benzo[b]carbazol- 11-one B 4.83 467.3 A6 A7-17 A10-1 951 GT2-8 [00966] 5-Ethyl-8- methoxy-6,6- dimethyl-5,6- dihydro- benzo[b]carbazol- 11-one F 2.94 320.0 A10-1 952 GT2-9 [00967] 8-(2- Diethylamino- ethoxy)-5-ethyl- 6,6-dimethyl-5,6- dihydro- benzo[b]carbazol- 11-one F 2.16 405.0 A6 A7-17 A10-1 953 GT2-10 [00968] 8-(2- Diethylamino- ethoxy)-5- isopropyl-6,6- dimethyl-5,6- dihydro- benzo[b]carbazol- 11-one A 2.02 419.0 A6 A7-17 A10-1 954 GT2-11 [00969] 8-((R)-2,3- Dihydroxy- propoxy)-6,6- dimethyl-5,6- dihydro- benzo[b]carbazol- 11-one C 2.17 352.2 A6 A7-17 A7-14-2 955 GT2-12 [00970] 5- Methanesulfonyl- 8-methoxy-6,6- dimethyl-5,6- dihydro- benzo[b]carbazol- 11-one C 2.87 370.1 A9-1 956 GT2-13 [00971] 8-(2- Diethylamino- ethoxy)-5- methanesulfonyl- 6,6-dimethyl-5,6- dihydro- benzo[b]carbazol- 11-one F 2.20 455.1 A6 A7-17 A9-1 957 GT2-14 [00972] 8-(2- Diethylamino- ethoxy)-5-(2- hydroxy-ethyl)- 6,6-dimethyl-5,6- dihydro- benzo[b]carbazol- 11-one H 3.73 421.0 A.6 A7-17 A10-1 958 GT2-15 [00973] 6,6-Dimethyl-8- ((2R,3R)-2,3,4- trihydroxy- butoxy)-5,6- dihydro- benzo[b]carbazol- 11-one H 3.73 332.4 A7-1 A7-14-2

[4225] The compounds described in the following Table 20 were synthesized according to the method shown below. Specifically, by using Compound A2 and phenylhydrazine having a corresponding substituent group, 2 (or 3)-substituted-8-methoxy-6,6-dimethyl-6,11-dihydro-5H-benzo[b]carbazol-11-one was prepared according to the method that is used for the synthesis of Compound A3 and Compound A4. Subsequently, to obtain the compounds of the Table, chemical conversion of the above compounds was achieved by using in combination the functional group modifications as explained before and described in the Table.

TABLE-US-00020 TABLE 20 Exam- HPLC Reten- ple Comp. Condi- tion No. No. Structure Compound Name tion Time m/z Method 959 GT3-1 [00974] 8-Methoxy-3,6,6- trimethyl-5,6- dihydro- benzo[b]carbazol- 11-one A 2.39 306.0 A3 A4 960 GT3-2 [00975] 8-(2-Diethylamino- ethoxy)-3,5,6,6- tetramethyl-5,6- dihydro- benzo[b]carbazol- 11-one A 1.97 405.0 A6 A7-17 A10-1 961 GT3-3 [00976] 8-(2-Diethylamino- ethoxy)-6,6- dimethyl-3-nitro- 5,6-dihydro- benzo[b]carbazol- 11-one B 3.86 422.2 A6 A7-17 962 GT3-4 [00977] 8-(2-Diethylamino- ethoxy)-6,6- dimethyl-3- trifluoromethyl-5,6- dihydro- benzo[b]carbazol- 11-one A 2.03 445.0 A6 A7-17 963 GT3-5 [00978] 8-(2-Diethylamino- ethoxy)-5-(2- diethylamino- ethyl)-6,6- dimethyl-3-nitro- 5,6-dihydro- benzo[b]carbazol- 11-one F 1.74 521.3 A6 A7-17 A10-1 964 GT3-6 [00979] 2,6,6-Trimethyl-8- ((2R,3R)-2,3,4- trihydroxy-butoxy)- 5,6-dihydro- benzo[b]carbazol- 11-one F 2.03 396.0 A6 A7-17 A7-14- 2 965 GT3-7 [00980] 2-Fluoro-6,6- dimethyl-8- ((2R,3R)-2,3,4- trihydroxy-butoxy)- 5,6-dihydro- benzo[b]carbazol- 11-one F 1.99 400.0 A6 A7-17 A7-14- 2 966 GT3-8 [00981] 2-Chloro-6,6- dimethyl-8- ((2R,3R)-2,3,4- trihydroxy-butoxy)- 5,6-dihydro- benzo[b]carbazol- 11-one F 2.14 416.0 A6 A7-17 A7-14- 2 967 GT3-9 [00982] 6,6-Dimethyl-11- oxo-8-((2R,3R)- 2,3,4-trihydroxy- butoxy)-6,11- dihydro-5H- benzo[b]carbazole- 2-carbonitrile F 1.90 407.4 A6 A7-17 A7-14- 2 968 GT3- 10 [00983] 6,6-Dimethyl-3- trifluoromethoxy-8- ((2R,3R)-2,3,4- trihydroxy-butoxy)- 5,6-dihydro- benzo[b]carbazol- 11-one F 2.31 466.4 A6 A7-17 A7-14- 2 969 GT3- 11 [00984] 8-((R)-2,3- Dihydroxy- propoxy)-6,6- dimethyl-3- trifluoromethoxy- 5,6-dihydro- benzo[b]carbazol- 11-one F 2.43 436.4 A6 A7-17 A7-14- 2 970 GT3- 12 [00985] 8-((R)-2,3- Dihydroxy- propoxy)-3- methoxy-5,6,6- trimethyl-5,6- dihydro- benzo[b]carbazol- 11-one B 3.79 396.5 A6 A7-17 A10-1 A7-14- 2 971 GT3- 13 [00986] 8-((R)-2,3- Dihydroxy- propoxy)-3- methoxy-6,6- dimethyl-5,6- dihydro- benzo[b]carbazol- 11-one B 3.40 382.4 A6 A7-17 A7-14- 2

[4226] The compounds described in the following Table 21 were synthesized according to the method shown below. Specifically, by using Compound E1 and phenylhydrazine having a corresponding substituent group, 9-bromo-1-chloro-8-methoxy-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one or 9-bromo-8-methoxy-6,6-dimethyl-3-trifluoromethoxy-5,6-dihydro-benzo[b]carbazol-11-one was prepared according to the method used for the synthesis of Compound A3 and Compound A4. Subsequently, to obtain the compounds of the Table, chemical conversion of the above compounds was achieved by using in combination the functional group modifications as explained before and described in the Table.

TABLE-US-00021 TABLE 21 Exam- HPLC Reten- ple Comp. Condi- tion No. No. Structure Compound Name tion Time m/z Method 972 GT4-1 [00987] 9-Bromo-8-((R)- 2,3-dihydroxy- propoxy)-6,6- dimethyl-3- trifluoromethoxy- 5,6-dihydro- benzo[b]carbazol- 11-one C 2.68 514.0 A6 A7-17 A7-14-2 973 GT4-2 [00988] 9-Bromo-1- chloro-8-((R)-2,3- dihydroxy- propoxy)-6,6- dimethyl-5,6- dihydro- benzo[b]carbazol- 11-one C 2.58 464.0 A6 A7-17 A7-14-2

[4227] The compounds described in the following Tables 22-23 were synthesized according to the method shown below. Specifically, catalytic reduction of Compound GT3-3 was carried out according to the method used for the preparation of Compound D2 to prepare Compound GT5-1.

[4228] Reductive alkylation of Compound GT5-1 was carried out according to the method used for the preparation of Compound B3-32 for the introduction of a methyl group or a benzyl group (Compound GT5-2, Compound GT5-3).

[4229] Catalytic reduction of Compound GT5-3 was carried out according to the method used for the preparation of Compound D2, and then processed to prepare Compound GT5-4.

[4230] The resulting amino derivatives of Compound GT5-1 to 4 were reacted with corresponding acyl chloride, isocynate, or chloroformate according to the method used for the preparation of Compound A9-1 to obtain the compounds of the Table.

TABLE-US-00022 TABLE 22 Exam- HPLC Reten- ple Comp. Condi- tion No. No. Structure Compound Name tion Time m/z Method 974 GT5-1 [00989] 3-Amino-8-(2- diethylamino- ethoxy)-6,6- dimethyl-5,6- dihydro- benzo[b]carbazol- 11-one A 1.15 392.3 D2 975 GT5-2 [00990] 8-(2-Diethylamino- ethoxy)-3- dimethylamino-6,6- dimethyl-5,6- dihydro- benzo[b]carbazol- 11-one A 1.18 420.2 B3-32 976 GT5-3 [00991] 3-(Benzyl-methyl- amino)-8-(2- diethylamino- ethoxy)-6,6- dimethyl-5,6- dihydro- benzo[b]carbazol- 11-one B 3.05 496.4 B3-32 977 GT5-4 [00992] 8-(2-Diethylamino- ethoxy)-6,6- dimethyl-3- methylamino-5,6- dihydro- benzo[b]carbazol- 11-one B 2.46 406.3 B3-32 D2 978 GT5-5 [00993] Pentanoic acid [8- (2-diethylamino- ethoxy)-6,6- dimethyl-11-oxo- 6,11-dihydro-5H- benzo[b]carbazol- 3-yl]amide C 2.52 476.5 A9-1 979 GT5-6 [00994] N-[8-(2- Diethylamino- ethoxy)-6,6- dimethyl-11-oxo- 6,11-dihydro-5H- benzo[b]carbazol- 3-yl]-2,2-dimethyl- propionamide A 1.74 476.4 A9-1 980 GT5-7 [00995] [8-(2- Diethylamino- ethoxy)-6,6- dimethyl-11-oxo- 6,11-dihydro-5H- benzo[b]carbazol- 3-yl]-carbamic acid 2-methoxy-ethyl A 1.55 494.3 A9-1 ester 981 GT5-8 [00996] 1-[8-(2- Diethylamino- ethoxy)-6,6- dimethyl-11-oxo- 6,11-dihydro-5H- benzo[b]carbazol- 3-yl]-3-phenyl-urea B 3.79 511.3 A9-1 982 GT5-9 [00997] N-[8-(2- Diethylamino- ethoxy)-6,6- dimethyl-11-oxo- 6,11-dihydro-5H- benzo[b]carbazol- 3-yl]-2-phenyl- acetamide B 3.81 510.4 A9-1 983 GT5-10 [00998] N-[8-(2- Diethylamino- ethoxy)-6,6- dimethyl-11-oxo- 6,11-dihydro-5H- benzo[b]carbazol- 3-yl]-3- trifluoromethyl- benzamide B 4.47 564.4 A9-1 984 GT5-11 [00999] 1-[8-(2- Diethylamino- ethoxy)-6,6- dimethyl-11-oxo- 6,11-dihydro-5H- benzo[b]carbazol- 3-yl]-3-(3- trifluoromethyl- phenyl)-urea B 4.55 579.4 A9-1 985 GT5-12 [01000] [8-(2- Diethylamino- ethoxy)-6,6- dimethyl-11-oxo- 6,11-dihydro-5H- benzo[b]carbazol- 3-yl]-carbamic acid 3-trifluoromethyl- H 5.17 580.1 A9-1 phenyl ester 986 GT5-13 [01001] N-[8-(2- Diethylamino- ethoxy)-6,6- dimethyl-11-oxo- 6,11-dihydro-5H- benzo[b]carbazol- 3-yl]-2-phenoxy- acetamide C 2.57 526.1 A9-1 987 GT5-14 [01002] 1-[8-(2- Diethylamino- ethoxy)-6,6- dimethyl-11-oxo- 6,11-dihydro-5H- benzo[b]carbazol- 3-yl]-1-methyl-3- phenyl-urea B 3.83 525.6 A9-1

TABLE-US-00023 TABLE 23 Exam- HPLC Reten- ple Comp. Condi- tion No. No. Structure Compound Name tion Time m/z Method 988 GT5-15 [01003] 1-[8-(2- Diethylamino- ethoxy)-6,6- dimethyl-11-oxo- 6,11-dihydro-5H- benzo[b]carbazol- 3-yl]-1-methyl-3- (3-trifluoromethyl- phenyl)-urea B 4.58 593.4 A9-1 989 GT5-16 [01004] 3-Benzyl-1-[8-(2- diethylamino- ethoxy)-6,6- dimethyl-11-oxo- 6,11-dihydro-5H- benzo[b]carbazol- 3-yl]-1-methyl- urea B 3.81 539.4 A9-1 990 GT5-17 [01005] N-[8-(2- Diethylamino- ethoxy)-6,6- dimethyl-11-oxo- 6,11-dihydro-5H- benzo[b]carbazol- 3-yl]N-methyl-3- trifluoromethyl- benzamide B 4.15 578.3 A9-1 991 GT5-18 [01006] N-[8-(2- Diethylamino- ethoxy)-6,6- dimethyl-11-oxo- 6,11-dihydro-5H- benzo[b]carbazol- 3-yl]N-methyl-2- phenoxy- acetamide C 2.62 540.4 A9-1 992 GT5-19 [01007] 3-(4-tert-Butyl- phenyl)-1-[8-(2- diethylamino- ethoxy)-6,6- dimethyl-11-oxo- 6,11-dihydro-5H- benzo[b]carbazol- 3-yl]-1-methyl- urea F 2.45 581.6 A9-1 993 GT5-20 [01008] 1-[8-(2- Diethylamino- ethoxy)-6,6- dimethyl-11-oxo- 6,11-dihydro-5H- benzo[b]carbazol- 3-yl]-3-(4- methoxy-phenyl)- 1-methyl-urea B 3.77 555.4 A9-1 994 GT5-21 [01009] [8-(2- Diethylamino- ethoxy)-6,6- dimethyl-11-oxo- 6,11-dihydro-5H- benzo[b]carbazol- 3-yl]carbamic acid phenyl ester A 1.89 512.2 A9-1

[4231] The compounds described in the following Table 24 were synthesized according to the method shown below. Specifically, having Compound T22-1 as a starting material, 8-[(4R,5R)-5-(tert-butyl-dimethylsilanyloxymethyl)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy]-6,6-dimethyl-5,6-dihydro-11-oxo-benzo[b]carbazole-3-carboxylic acid was prepared according to the method that is used for the preparation of Compound B2-28.

[4232] The resulting carboxylic acid was subjected to dehydrating condensation with corresponding amine, alcohol according to the method that is used for the preparation of Compound A9-10. Subsequently, deprotection was carried out according to the method used for the preparation of Compound T22-1-1 and Compound T22-1-2 to obtain the compounds described in the Table.

TABLE-US-00024 TABLE 24 Exam- HPLC Reten- ple Comp. Condi- tion No. No. Structure Compound Name tion Time m/z Method 995 GT6-1 [01010] 6,6-Dimethyl-11-oxo-8- ((2R,3R)-2,3,4- trihydroxy-butoxy)-6,11- dihydro-5H-benzo[b] carbazole-3-carboxylic acid phenylamide A 1.79 501.0 A8-10 996 GT6-2 [01011] 6,6-Dimethyl-11-oxo-8- ((2R,3R)-2,3,4- trihydroxy-butoxy)-6,11- dihydro-5H-benzo[b] carbazole-3-carboxylic acid dimethylamide D 1.33 453.0 A9-10 997 GT6-3 [01012] 6,6-Dimethyl-11-oxo-8- ((2R,3R)-2,3,4- trihydroxy-butoxy)-6,11- dihydro-5H-benzo[b] carbazole-3-carboxylic acid 2-hydroxy-ethyl ester A 1.40 470.0 A9-10 998 GT6-4 [01013] 6,6-Dimethyl-11-oxo-8- ((2R,3R)-2,3,4- trihydroxy-butoxy)-6,11- dihydro-5H-benzo[b] carbazole-3-carboxylic acid butylamide D 1.55 481.0 A9-10 999 GT6-5 [01014] 6,6-Dimethyl-11-oxo-8- ((2R,3R)-2,3,4- trihydroxy-butoxy)-6,11- dihydro-5H-benzo[b] carbazole-3-carboxylic acid (2-methoxy-ethyl)- amide D 1.30 483.0 A9-10 1000 GT6-6 [01015] 6,6-Dimethyl-11-oxo-8- ((2R,3R)-2,3,4- trihydroxy-butoxy)-6,11- dihydro-5H-benzo[b] carbazole-3-carboxylic acid methylamide D 1.24 439.0 A9-10 1001 GT6-7 [01016] 6,6-Dimethyl-11-oxo-8- ((2R,3R)-2,3,4- trihydroxy-butoxy)-6,11- dihydro-5H-benzo[b] carbazole-3-carboxylic acid benzylamide D 1.58 515.0 A9-10 1002 GT6-8 [01017] 6,6-Dimethyl-11-oxo-8- ((2R,3R)-2,3,4- trihydroxy-butoxy)-6,11- dihydro-5H-benzo[b] carbazole-3-carboxylic acid amide D 1.18 425.0 A9-10 1003 GT6-9 [01018] 6,6-Dimethyl-11-oxo-8- ((2R,3R)-2,3,4- trihydroxy-butoxy)-6,11- dihydro-5H-benzo[b] carbazole-3-carboxylic acid pyridin-4-ylamide D 1.40 502.0 A9-10 1004 GT6-10 [01019] 6,6-Dimethyl-11-oxo-8- ((2R,3R)-2,3,4- trihydroxy-butoxy)-6,11- dihydro-5H-benzo[b] carbazole-3-carbolic acid D 1.01 426.0 E2-28 1005 GT6-11 [01020] 6,6-Dimethyl-11-oxo-8- ((2R,3R)-2,3,4- trihydroxy-butoxy)-6,11- dihydro-5H-benzo[b] carbazole-3-carboxylic acid pyridin-2-ylamide D 1.52 502.0 A9-10 1006 GT6-12 [01021] 6,6-Dimethyl-11-oxo-8- ((2R,3R)-2,3,4- trihydroxy-butoxy)-6,11- dihydro-5H-benzo[b] carbazole-3-carboxylic acid pyridin-3-ylamide D 1.34 502.0 A9-10 1007 GT6-13 [01022] 6,6-Dimethyl-11-oxo-8- ((2R,3R)-2,3,4- trihydroxy-butoxy)-6,11- dihydro-5H-benzo[b] carbazole-3-carboxylic acid phenethyl-amide D 1.67 529.0 A9-10 1008 GT6-14 [01023] N-[6,6-Dimethyl-11- oxo-8-((2R,3R)-2,3,4- trihydroxy-butoxy)-6,11- dihydro-5H-benzo[b] carbazole-3-carbonyl]- benzenesulfonamide D 1.23 565.0 A9-10

[4233] To the compounds described in the following Table 25, a hydroxyl group was introduced from Compound T17-3 according to the method described in JACS 2006, Vol. 128, page 10964. Subsequently, deprotection was carried out according to the method used for Compound A7-14-2 and Compound T22-2 to obtain the compounds shown below.

TABLE-US-00025 TABLE 25 Exam- HPLC Reten- ple Comp. Condi- tion No. No. Structure Compound Name tion Time m/z 1009 GT7-1 [01024] 8-((R)-2,3-Dihydroxy- propoxy)-3- hydroxy-6,6-dimethyl- 5,6-dihydro- benzo[b]carbazol-11-one B 2.59 368.4 1010 GT7-2 [01025] 8-((R)-2,3-Dihydroxy- propoxy)-3- hydroxy-5,6,6-trimethyl- 5,6-dihydro- benzo[b]carbazol-11-one C 1.90 382.4

[4234] The compounds described in the following Table 26 were prepared by alkylation according to the method used for the preparation of Compound A7-1 from Compound GT7-1 or Compound GT7-2, or by carbamation according to the method used for the preparation of A9-1.

TABLE-US-00026 TABLE 26 Exam- HPLC Reten- ple Comp. Condi- tion No. No. Structure Compound Name tion Time m/z Method 1011 GT8-1 [01026] 8-((R)-2,3- Dihydroxy-propoxy)- 3-ethoxy- 5,6,6-trimethyl- 5,6-dihydro- benzo[b]carbazol- 11-one C 2.43 410.5 A7-1 1012 GT8-2 [01027] 8-((R)-2,3- Dihydroxy- propoxy)-3- ethoxy-6,6-dimethyl- 5,6-dihydro- benzo[b]carbazol- 11-one C 2.30 386.5 A7-1 1013 GT8-3 [01028] 8-((R)-2,3- Dihydroxy- propoxy)-5,6,6- trimethyl-3-(oxetan- 3-yloxy)-5,6- dihydro-benzo[b] carbazol- 11-one B 1.72 438.5 A7-1 1014 GT8-4 [01029] Phenyl-carbamic acid 8-((R)- 2,3-dihydroxy- propoxy)-6,6- dimethyl-11- oxo-6,11- dihydro-5H- benzo[b]carbazol- 3-yl ester E 4.23 487.0 A8-1

Example 1015

Compound GT9-1

8-((R)-2,3-Dihydroxy-propoxy)-6,6-dimethyl-3-(2H-tetrazol-5-yl)-5,6-dihydro-benzo[b]carbazol-11-one

[4235] ##STR01030##

[4236] 8-((S)-2,2-Dimethyl-[1,3]dioxolan-4-yl methoxy)-6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazole-3-carbonitrile (20.0 mg, 0.048 mmol), ammonium chloride (1.28 mg, 0.024 mmol) and NaN.sub.3 (6.24 mg, 0.096 mmol) were dissolved in DMF, and the mixture was stirred at 120 C. for 14 hrs. NaN.sub.3 (6.24 mg, 0.096 mmol) was further added to the mixture, which was then stirred at 120 C. for 30 hrs. The reaction solution was added with 1 N aqueous solution of hydrochloric acid and extracted with ethyl acetate. The organic layer was washed with saturated brine and concentrated under reduced pressure. The resultant solid obtained after concentration was washed with hexane:ethyl acetate=1:1 to obtain 8-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy)-6,6-dimethyl-3-(2H-tetrazol-5-yl)-5,6-dihydro-benzo[b]carbazol-11-one as a white solid.

[4237] The product was suspended in MeOH (1.0 ml), added with 1 N aqueous solution of hydrochloric acid, and then stirred at 60 C. for 1 hr and 30 min. After cooling to room temperature, the reaction solution was concentrated under reduced pressure, and the resulting solid was washed with DCM to obtain the title compound as a pale yellow solid (13.4 mg, 66.3%).

[4238] LCMS: m/z 420 [M+H].sup.+

Example 1016

Compound GT9-2

8-((R)-2,3-Dihydroxy-propoxy)-6,6-dimethyl-3-thiophen-3-yl-5,6-dihydro-benzo[b]carbazol-11-one

[4239] ##STR01031##

[4240] 3-Bromo-8-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy)-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one (20.0 mg, 0.043 mmol), thiophene-3-boronic acid (10.9 mg, 0.085 mmol), K.sub.3PO.sub.4 (40 mg) and Pd (PPh.sub.3).sub.4 (9.9 mg, 0.0086 mmol) were dissolved in DMA (0.8 ml) and water (0.2 ml), and stirred at 140 C. for 10 min under microwave irradiation. The reaction solution was diluted with ethyl acetate and washed with saturated brine. The organic layer was concentrated under reduced pressure, and the resulting residues were purified by column chromatography (hexane/ethyl acetate) to obtain 8-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy)-6,6-dimethyl-3-thiphen-3-yl-5,6-dihydro-benzo[b]carbazol-11-one.

[4241] This product was suspended in MeOH (1.0 ml), added with 1 N hydrochloric acid, and then stirred at 60 C. for 1 hr and 30 min. The reaction solution was concentrated under reduced pressure, and the resulting solid was washed with DCM to obtain the title compound as a yellow solid (12.6 mg, 67.1%).

[4242] LCMS: m/z 434 [M+H].sup.+

[4243] Using the combination of Compound T18-1 and corresponding boronic acid or the combination of (S)-8-((2,2-dimethyl-1,3-dioxolan-4-yl)methoxy)-6,6-dimethyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5H-benzo[b]carbazol-11 (6H)-one and corresponding bromide, the reaction was carried out in the same manner as Compound GT9-2 to obtain the compounds of the following Table 27.

TABLE-US-00027 TABLE 27 Exam- HPLC Reten- ple Comp. Condi- tion No. No. Structure Compound Name tion Time m/z 1017 GT9-3 [01032] 8-((R)-2,3- Dihydroxy-propoxy)- 6,6-dimethyl-3- thiophen-2-yl- 5,6-dihydro- benzo[b]carbazol- 11-one B 4.59 434.0 1018 GT9-4 [01033] 8-((R)-2,3- Dihydroxy-propoxy)- 6,6-dimethyl-3- (1H-pyrazol- 4-yl)-5,6-dihydro- benzo[b]carbazol- 11-one B 4.04 418.0 1019 GT9-5 [01034] 8-((R)-2,3- Dihydroxy-propoxy)- 6,6-dimethyl-3- (2H-pyrazol-3-yl)- 5,6-dihydro-benzo[b] carbazol-11-one A 1.51 418.0 1020 GT9-6 [01035] 8-((R)-2,3- Dihydroxy-propoxy)- 6,6-dimethyl-3- thiazol-5- yl-5,6-dihydro- benzo[b] carbazol-11-one F 1.97 435.0 1021 GT9-7 [01036] 8-((R)-2,3- Dihydroxy-propoxy)- 3-(3H-imidazol- 4-yl)-6,6- dimethyl-5,6- dihydro-benzo[b] carbazol-11-one H 2.91 418.0

Example 1022

Compound GT10-1

8-((2R,3R)-2,3,4-Trihydroxybutoxy)-2,3,5,6-tetrahydrospiro[benzo[b]carbazole-6,4-pyran]-11 (5H)-one

[4244] ##STR01037##

[4245] Preparation was carried out in the same manner as Compound N6-1-2.

[4246] LCMS: m/z 434 [M+H].sup.+

[4247] HPLC retention time: 1.56 min (analysis condition A)

[4248] The compounds described in the following Table 28were synthesized according to the method shown below. Specifically, by using the method for the preparation of Compound Z10, Z11, Z12 and Z13, 8-hydroxy-6,6-dimethyl-6H-benzo[b]naphtho[2,3-d]furan-11-one was prepared from Compound A2 and bromophenol. To the resulting compound, a side chain or a synthetic equivalent thereof was introduced according to Mitsunobu reaction that is used for the preparation of Compound A7-1 or the method that is used for A7-17, etc. After that, if necessary, functional group modification such as deprotection, etc. was carried out to prepare the compounds listed below.

TABLE-US-00028 TABLE 28 Exam- HPLC Reten- ple Comp. Condi- tion No. No. Structure Compound Name tion Time m/z 1023 GT11-1 [01038] (R)-5-(6,6-Dimethyl- 11-oxo-6,11-dihydro- benzo[b]naphtho[2,3-d] furan-8-yloxy)-4-hydroxy- pentanoic acid H 5.37 395.0 1024 GT11-2 [01039] (R)-5-(6,6-Dimethyl- 11-oxo-6,11-dihydro- benzo[b]naphtho[2,3-d] furan- 8-yloxymethyl)- pyrrolidin-2-one H 5.50 376.0 1025 GT11-3 [01040] 8-(3-Hydroxy-propoxy)- 6,6-dimethyl- 6H-benzo[b]naphtho [2,3-d]furan-11-one H 5.97 337.0 1026 GT11-4 [01041] 8-(3-Ethyl-3-hydroxy- pentyloxy)-6,6- dimethyl-6H-benzo[b] naphtho[2,3- d]furan-11-one H 9.29 393.0 1027 GT11-5 [01042] (6,6-Dimethyl-11-oxo- 6,11-dihydro- benzo[b]naphtho[2,3-d] furan-8-yloxy)- acetic acid H 5.65 336.0 1028 GT11-6 [01043] 4-(6,6-Dimethyl-11-oxo- 6,11-dihydro- benzo[b]naphtho[2,3-d] furan-8-yloxy)- butyric acid H 6.15 365.0 1029 GT11-7 [01044] 5-(6,6-Dimethyl-11- oxo-6,11-dihydro- benzo[b]naphtho[2,3-d] furan-8-yloxy)- pentanoic acid H 6.44 379.0 1030 GT11-8 [01045] 6-(6,6-Dimethyl-11- oxo-6,11-dihydro- benzo[b]naphtho[2,3-d] furan-8-yloxy)- hexanoic acid H 6.77 393.0 1031 GT11-9 [01046] 2-(6,6-Dimethyl-11- oxo-6,11-dihydro- benzo[b]naphtho[2,3-d] furan-8-yloxy)- N,N-diethyl-acetamide H 6.39 392.0 1032 GT11-10 [01047] 6,6-Dimethyl-8- (2-morpholin-4-yl- ethoxy)-6H-benzo[b] naphtho[2,3- d]furan-11-one H 4.45 392.0 1033 GT11-11 [01048] 8-(2-Dimethylamino- ethoxy)-6,6- dimethyl-6H-benzo[b] naphtho[2,3- d]furan-11-one H 4.59 350.0

TABLE-US-00029 TABLE 29 Example Comp. HPLC Retention No. No. Structure Compound Name Condition Time m/z 1034 GT11- 12 [01049] 8-((S)-2,3-Dihydroxy- propoxy)-6,6- dimethyl-6H- benzo[b]naphtho[2,3-d] furan-11-one F 2.40 353.0 1035 GT11- 13 [01050] 8-((R)-2,3-Dihydroxy- propoxy)-6,6- dimethyl-6H- benzo[b]naphtho[2,3-d] furan-11-one H 5.07 353.0 1036 GT11- 14 [01051] 6,6-Dimethyl-8- (2-pyrrolidin-1-yl-ethoxy)- 6H-benzo[b]naphtho [2,3-d]furan-11-one C 3.03 375.9 1037 GT11- 15 [01052] 6,6-Dimethyl-8- (2-piperidin-1-yl-ethoxy)- 6H-benzo[b]naphtho[2,3-d] furan-11-one C 3.15 389.9 1038 GT11- 16 [01053] 8-(3-Dimethylamino- propoxy)-6,6-dimethyl- 6H-benzo[b]naphtho[2,3-d] furan-11-one C 3.30 364.2 1039 GT11- 17 [01054] 8-(2-Azepan-1-yl-ethoxy)- 6,6-dimethyl-6H- benzo[b]naphtho[2,3-d] furan-11-one F 2.35 404.3 1040 GT11- 18 [01055] (6,6-Dimethyl-11-oxo- 6,11-dihydro- benzo[b]naphtho[2,3-d] furan-8-yloxy)- acetic acid methyl ester D 2.38 351.0 1041 GT11- 19 [01056] 2-(6,6-Dimethyl-11-oxo- 6,11-dihydro- benzo[b]naphtho [2,3-d]furan-8-yloxy)- N-(2-morpholin- 4-yl-ethyl)-acetamide D 2.03 450.0 1042 GT11- 20 [01057] 6,6-Dimethyl-8- (2-piperazin-1-yl-ethoxy)- 6H-benzo[b]naphtho [2,3-d]furan-11-one C 2.81 391.2 1043 GT11- 21 [01058] 8-[2-(4-Methanesulfonyl- piperazin-1-yl)-ethoxy]- 6,6-dimethyl-6H- benzo[b]naphtho[2,3-d] furan-11-one F 2.21 469.1 1044 GT11- 22 [01059] 2-(6,6-Dimethyl-11-oxo- 6,11-dihydro-benzol[b] naphtho[2,3-d]furan- 8-yloxy)- acetamide O 1.95 336.0 1045 GT11- 23 [01060] 4-[2-(6,6-Dimethyl-11-oxo- 6,11-dihydro- benzo[b]napntho[2,3-d] furan-8-yloxy)-ethyl]- piperazine- 1-carboxylic acid amide F 2.04 434.0 1046 GT11- 24 [01061] N-(2,3-Dihydroxy-propyl)- 2-(6,6-dimethyl-11-oxo- 6,11-dihydro- benzo[b]naphtho [2,3-d]furan- 8-yloxy)- acetamide D 1.82 410.0

TABLE-US-00030 TABLE 30 Example Comp. HPLC Retention No. No. Structure Compound Name Condition Time m/z 1047 GT11- 25 [01062] 8-[2-(4-Acetyl-piperazin- 1-yl)-ethoxy]-6,6-dimethyl- 6H-benzo[b]naphtho[2,3- d]furan-11-one F 2.10 433.1 1048 GT11- 26 [01063] 4-[2-(6,6-Dimethyl-11-oxo- 6,11-dihydro- benzo[b]naphtho[2,3-d]furan- 8-yloxy)-acetyl]-piperazine- 1-carboxylic acid tert-butyl ester D 2.53 505.0 1049 GT11- 27 [01064] 8-[2-(2-Hydroxy-ethoxy)- ethoxy]-6,6-dimethyl- 6H-benzo[b]naphtho [2,3-d]furan-11-one H 5.62 367.0 1050 GT11- 28 [01065] 8-{2-[2-(2-Hydroxy-ethoxy)- ethoxy]-ethoxy}-6,6-dimethyl- 6H-benzo[b]naphtho [2,3-d]furan-11-one H 5.64 411.0 1051 GT11- 29 [01066] 8-(2-Imidazol-1-yl-ethoxy)- 6,6-dimethyl-6H-benzo[b] naphtho[2,3-d]furan-11-one F 2.05 373.1 1052 GT11- 30 [01067] 2-(6,6-Dimethyl-11-oxo- 6,11-dihydro-benzo[b]naphtho [2,3-d]furan-8-yloxy)- N-(2-pyridin-4-yl-ethyl) -acetamide D 2.10 441.0 1053 GT11- 31 [01068] N-(2-Dimethylamino- ethyl)-2-(6,6-dimethyl-11- oxo-6,11-dihydro- benzo[b]naphtho[2,3-d]furan- 8-yloxy)-acetamide D 2.01 407.0 1054 GT11- 32 [01069] 2-(6,6-Dimethyl-11-oxo- 6,11-dihydro- benzo[b]naphtho[2,3-d]furan- 8-yloxy)-N-[2-(2-hydroxy- ethoxy)-ethyl]- acetamide D 1.88 424.0 1055 GT11- 33 [01070] 6,6-Dimethyl-8-[2- (4-methyl-piperazin-1-yl)- ethoxy]-6H-benzo[b]naphtho [2,3-d]furan-11-one F 1.99 405.2 1056 GT11- 34 [01071] 6,6-Dimethyl-8-((2R,3R)- 2,3,4-trihydroxy-butoxy)- 6H-benzo[b]naphtho[2,3-d] furan-11-one F 2.21 383.0 1057 GT11- 35 [01072] 8-((R)-2-Hydroxy-3- piperidin-1-yl-propoxy)- 6,6-dimethyl-6H- benzo[b]naphtho[2,3-d] furan-11-one F 2.25 420.0 1058 GT11- 36 [01073] 6,6-Dimethyl-8-(2-oxo-2- piperazin-1-yl-ethoxy)-6H- benzo[b]naphtho[2,3-d] furan-11-one D 1.92 405.0 1059 GT11- 37 [01074] 8-{2-[4-(2-Hydroxy-acetyl)- piperazin-1-yl]-ethoxy}- 6-dimethyl-6H- benzo[b]naphtho[2,3-d] furan-11-one F 2.06 449.1 1060 GT11- 38 [01075] 8-((S)-2-Hydroxy-3- piperidin-1-yl- propoxy)-6,6-dimethyl- 6H-benzo[b]naphtho[2,3-d] furan-11-one F 2.24 420.0

TABLE-US-00031 TABLE 31 Example Comp. HPLC Retention No. No. Structure Compound Name Condition Time m/z 1061 GT11- 39 [01076] 8-[2-((R)-2,3-Dihydroxy- propylamino)-ethoxy]- 6,6-dimethyl-6H- benzo[b]naphtho[2,3-d] furan-11-one H 4.18 396.0 1062 GT11- 40 [01077] 8-((S)-4,5-Dihydroxy- pentyloxy)-6,6-dinethyl- 6H-benzo[b]naphtho [2,3-d]furan-11-one F 2.56 381.0 1063 GT11- 41 [01078] 4-[2-(6,6-Dimethyl-11-oxo- 6,11-dihydro-benzo[b] naphtho[2,3-d]furan-8-yloxy)- ethyl]-piperazin-2-one F 2.06 405.0 1064 GT11- 42 [01079] 2-(6,6-Dimethyl-11-oxo- 6,11-dihydro-benzo[b]naphtho [2,3-d]furan-8-yloxy)- N-piperidin-4-yl-acetamide D 1.92 419.0 1065 GT11- 43 [01080] N-{2-[Bis-(2-hydroxy-ethyl)- amino]-ethyl}-2-(6,6-dimethyl- 11-oxo-6,11-dihydro-benzo[b] naphtho[2,3-d]furan- 8-yloxy)-acetamide D 1.83 467.0 1066 GT11- 44 [01081] N-(3-Dimethylamino-propyl)- 2-(6,6-dimethyl-11-oxo- 6,11-dihydro-benzo[b]naphtho [2,3-d]furan-8-yloxy)- acetamide D 2.08 422.0 1067 GT11- 45 [01082] N-(2-Diethylamino-ethyl)- 2-(6,6-dimethyl-11- oxo-6,11-dihydro- benzo[b]naphtho[2,3-d] furan-8-yloxy)- acetamide D 2.10 436.0 1068 GT11- 46 [01083] 6,6-Dimethyl-8- (pyrimidin-2-yloxy)- 6H-benzo[b]naphtho[2,3-d] furan-11-one H 6.35 357.0 1069 GT11- 47 [01084] 8-(2-Ethylamino-ethoxy)- 6,6-dimethyl-6H-benzo[b] naphtho[2,3-d]furan-11- one F 2.15 350.0 1070 GT11- 48 [01085] 1-[2-(6,6-Dimethyl-11- oxo-6,11-dihydro-benzo[b] naphtho[2,3-d]furan-8-yloxy)- ethyl]-piperazin-2-one H 4.42 405.0 1071 GT11- 49 [01086] 4-[2-(6,6-Dimethyl-11- oxo-6,11-dihydro-benzo[b] naphtho[2,3-d]furan-8-yloxy)- ethyl]-1-methyl-piperazin-2-one H 4.33 419.0 1072 GT11- 50 [01087] 2-(6,6-Dimethyl-11-oxo- 6,11-dihydro-benzo[b]naphtho [2,3-d]furan-8-yloxy)-N- (2-piperazin-1-yl-ethyl)-acetamide A 3.99 448.0 1073 GT11- 51 [01088] 2-Dimethylamino-N- [2-(6,6-dimethyl-11-oxo- 6,11-dihydro-benzo[b] naphtho[2,3-d]furan-8-yloxy)- ethyl]-acetamide D 2.13 408.0 1074 GT11- 52 [01089] 4-[2-(6,6-Dimethyl-11- oxo-6,11-dihydro-benzo[b] naphtho[2,3-d]furan-8-yloxy)- ethyl]-1,1-dimethyl-3-oxo- piperazin-1-ium; chloride H 4.47 433.0

TABLE-US-00032 TABLE 32 Example Comp. HPLC Retention No. No. Structure Compound Name Condition Time m/z 1075 GT11- 53 [01090] 8-{2-[4-(2-Hydroxy-ethyl)- piperazin-1-yl]-ethoxy}- 6,6-dimethyl-6H- benzo[b]naphtho[2,3-d] furan-11-one A 1.75 435.0 1076 GT11- 54 [01091] 1-[2-(6,6-Dimethyl-11- oxo-6,11-dihydro- benzo[b]naphtho[2,3-d] furan-8-yloxy)-ethyl]-4- methyl-piperazin-2-one B 4.09 419.0 1077 GT11- 55 [01092] 6,6-Dimethyl-8- (3-piperazin-1-yl-propoxy)- 6H-benzol]naphtho[2,3-d] furan-11-one A 1.75 405.0 1078 GT11- 56 [01093] 8-{2-[4-((S)-2,3-Dihydroxy- propyl)-piperazin-1-yl]-ethoxy}- 6.6-dimethyl-6H-benzo[b] naphtho[2,3-d]furan-11-one A 1.72 465.0 1079 GT11- 57 [01094] 8-[2-(2-Hydroxy-1,1- dimethyl-ethylamino)-ethoxy]- 6,6-dimethyl-6H-benzo[b] naphtho[2,3-d]furan-11-one C 2.57 394.0 1080 GT11- 58 [01095] 8-{2-[Bis-(2-hydroxy-ethyl)- amino]-ethoxy}-6,6-dimethyl- 6H-benzo[b]naphtho[2,3-d] furan-11-one C 2.77 410.0 1081 GT11- 59 [01096] 8-[2-(3-Hydroxy-piperidin-1-yl)- ethoxy]-6,6-dimethyl-6H- benzo[d]naphtho[2,3-d] furan-11-one C 2.88 406.0 1082 GT11- 60 [01097] 8-[2-(2-Hydroxymethyl- pyrrolidin-1-yl)-ethoxy]- 6,6-dimethyl-6H-benzo[b] naphtho[2,3-d]furan-11-one C 2.82 406.0 1083 GT11- 61 [01098] 8-{2-[Ethyl-(2-hydroxy-ethyl)- amino]-ethoxy}-6,6-dimethyl- 6H-benzo[b]naphtho[2,3-d] furan-11-one C 2.85 394.0 1084 GT11- 62 [01099] 6,6-Dimethyl-8-(3-methyl- oxetan-3-ylmethoxy)- 6H-benzo[b]naphtho [2,3-d]furan-11-one C 3.03 363.0 1085 GT11- 63 [01100] 8-[2-(1-Hydroxymethyl- cyclopentylamino)- ethoxy]-6,6-dimethyl- 6H-benzo[b]naphtho [2,3-d]furan-11-one C 2.72 420.0 1086 GT11- 64 [01101] 8-(4-Hydroxy-pyrrolidin- 2-ylmethoxy)-6,6-dimethyl- 6H-benzo[d]naphtho [2,3-d]furan-11-one Y 2.96 378.0 1087 GT11- 65 [01102] 6,6-Dimethyl- 8-(piperidin-3-yloxy)- 6H-benzo[b]naphtho [2,3-d]furan-11-one Y 3.03 362.0

[4249] The compounds described in the following Table 33 were synthesized according to the method shown below. From Compound A2 and 2-bromophenol having a fluorine atom at corresponding position, 8-methoxy-6H-benzo[b]naphtho[2,3-d]furan-11-one having a fluorine atom at corresponding position (Compound GT12-1, GT12-2, GT12-5 and GT12-7) was prepared according to the method used for the preparation of Compound Z10, Z11 and Z12. Further, demethylation was carried out according to the method used for the preparation of Compound A6 to obtain 8-hydroxy-6H-benzo[b]naphtho[2,3-d]furan-11-one which has a fluorine atom at corresponding position. Thereafter, according to Mitsunobu reaction used for the preparation of Compound A7-1 or the alkylation method used for the preparation of Compound A7-17, a corresponding side chain was introduced and, if necessary, functional group modification such as deprotection, etc. was carried out to prepare the compounds listed below.

TABLE-US-00033 TABLE 33 Example Comp. HPLC Retention No. No. Structure Compound Name Condition Time m/z 1088 GT12-1 [01103] 3-Fluoro-8-methoxy- 6,6-dimethyl-6H- benzo[b]naphtho[2,3-d] furan-11-one A 3.02 311.0 1089 GT12-2 [01104] 4-Fluoro-8-methoxy- 6,6-dimethyl-6H- benzo[b]naphtho[2,3-d] furan-11-one A 3.00 311.0 1090 GT12-3 [01105] 8-(2-Diethylamino-ethoxy)- 3-fluoro-6,6-dimethyl- 6H-benzo[b]naphtho[2,3-d] furan-11-one B 4.48 396.0 1091 GT12-4 [01106] 3-Fluoro-6,6-dimethyl- 8-((2R,3R)-2,3,4-trihydroxy- butoxy)-6H-benzo[b]naphtho [2,3-d]furan-11-one H 4.91 401.4 1092 GT12-5 [01107] 2-Fluoro-8-methoxy- 6,6-dimethyl-6H-benzo[b] naphtho[2,3-d]furan-11-one C 3.01 311.0 1093 GT12-6 [01108] 8-(2-Diethylamino-ethoxy)- 2-fluoro-6,6-dimethyl-6H- benzo[b]naphtho[2,3-d] furan-11-one C 2.09 395.0 1094 GT12-7 [01109] 1-Fluoro-8-methoxy- 6,6-dimethyl-6H-benzo[b] naphtho[2,3-d]furan-11-one B 6.26 311.0 1095 GT12-8 [01110] 8-((R)-2,3-Dihydroxy-propoxy)- 2-fluoro-6,6-dimethyl- 6H-benzo[b]naphtho [2,3-d]furan-11-one C 2.22 371.0 1096 GT12-9 [01111] 8-(2-Diethylamino-ethoxy)- 1-fluoro-6,6-dimethyl-6H- benzo[b]naphtho[2,3-d] furan-11-one B 4.20 396.0 1097 GT12-10 [01112] 8-((R)-2,3-Dihydroxy-propoxy)- 3-fluoro-6,6-dimethyl-6H- benzo[b]naphtho[2,3-d] furan-11-one B 4.82 371.0 1098 GT12-11 [01113] 8-((R)-2,3-Dihydroxy-propoxy)- 4-fluoro-6,6-dimethyl-6H- benzo[d]naphtho[2,3-d] furan-11-one D 1.80 371.0 1099 GT12-12 [01114] 8-((R)-2,3-Dihydroxy-propoxy)- 1-fluoro-6,6-dimethyl-6H- benzo[d]naphtho[2,3-d] furan-11-one D 1.85 371.0

[4250] The compounds described in the following Table 34 were synthesized according to the method shown below. 8-Hydroxy-6H-benzo[b]naphtho[2,3-d]furan-11-one was transformed into trifluoromethanesulfonic acid ester according to the method used for the preparation of Compound B1. Subsequently, by carrying out the method used for the preparation of Compound B2-1 or Compound B2-18, Compound GT13-1, Compound GT13-2 and Compound GT13-3 were prepared. Compound GT13-3 was oxidized according to the method used for the preparation of Compound B3-8 to prepare Compound 13-4.

TABLE-US-00034 TABLE 34 Example Comp. HPLC Retention No. No. Structure Compound Name Condition Time m/z Method 1100 GT13-1 [01115] 6,6-Dimethyl-8- morpholin-4-yl-6H- benzo[b]naphtho [2,3-d]furan-11-one F 3.04 348.2 B1, B2-1 1101 GT13-2 [01116] 6,6-Dimethyl-8- (4-methyl-piperazin-1- yl)-6H-benzo[b]naphtho [2,3-d]furan-11-one F 2.13 361.3 B1, B2-1 1102 GT13-3 [01117] 8-(2-Diisopropylamino- ethylsulfanyl)-6,6- dimethyl-6H- benzo[b]naphtho[2,3-d] furan-11-one C 3.45 422.0 B1, B2-18 1103 GT13-4 [01118] 8-(2-Diisopropylamino- ethanesulfonyl)- 6,6-dimethyl-6H- benzo[b]naphtho[2,3-d] furan-11-one C 3.23 454.0 B3-8

[4251] The compounds described in the following Table 35 were synthesized according to the method shown below. Specifically, a side chain was introduced to Compound Z13 to prepare Compound GT13-5 according to the method that is used for the preparation of Compound A7-17. Further Compound GT13-5 or trifluoromethanesulfonic acid ester of Compound Z14 was hydrolyzed to prepare Compound GT13-6 and Compound GT13-7 according to the method used for the preparation of Compound T20.

TABLE-US-00035 TABLE 35 Example Comp. HPLC Retention No. No. Structure Compound Name Condition Time m/z Method 1104 GT13-5 [01119] Trifluoro-methanesulfonic acid 8-(2-diethylamino-ethoxy)-6,6- dimethyl-11-oxo-6,11-dihydro- benzo[b]naphtho[2,3-d] furan-3-yl ester H 5.37 526.0 A7-17 1105 GT13-6 [01120] 8-(2-Diethylamino-ethoxy)- 3-hydroxy-6,6-dimethyl-6H- benzo[b]naphtho[2,3-d] furan-11-one B 3.40 394.0 T20 1106 GT13-7 [01121] 3-Hydroxy-6,6-dimethyl-8- ((2R,3R)-2,3,4-trihydroxy- butoxy)-6H-benzo[b]naphtho [2,3-d]furan-11-one F 1.87 399.0 T20

[4252] The compounds described in the following Table 36 were prepared by subjecting Compound GT13-6 or GT13-7 to Mitsunobu reaction that is used for the preparation of Compound A7-1 to introduce a corresponding side chain or a synthetic equivalent. After that, by carrying out deprotection, if necessary, the compounds listed below were prepared.

TABLE-US-00036 TABLE 36 Exam- Comp. HPLC Retention Me- ple No. No. Structure Compound Name Condition Time m/z thod 1107 GT13- 8 [01122] 8-(2-Diethylamino- ethoxy)-3-methoxy- 6,6-dimethyl-6H- benzo[b]naphtho [2,3-d]furan-11-one H 4.72 408.0 A7-1 1108 GT13- 9 [01123] 3-Methoxy-6,6- dimethyl-8-((2R,3R)- 2,3,4-trihydroxy- butoxy)-6H-benzo[b] naphtho[2,3-d] furan-11-one B 4.23 413.2 A7-1 1109 GT13- 10 [01124] 8-(2-Diethylamino- ethoxy)-3-ethoxy- 6,6-dimethyl-6H- benzo[b]naphtho[2,3-d] furan-11-one H 5.10 422.0 A7-1 1110 GT13- 11 [01125] 8-(2-Diethylamino- ethoxy)-6,6-dimethyl- 3-propoxy- 6H-benzo[b]naphtho [2,3-d]furan-11-one H 5.63 436.0 A7-1 1111 GT13- 12 [01126] 3-(2-Hydroxy-ethoxy)- 6,6-dimethyl-8- ((2R,3R)-2,3,4- trihydroxy-butoxy)- 6H-benzo[b]naphtho [2,3-d]furan-11-one F 1.83 443.0 A7-1 1112 GT13- 13 [01127] 3-(3-Hydroxy-propoxy)- 6,6-dimethyl-8-((2R,3R)- 2,3,4-trihydroxy-butoxy)- 6H-benzo[b]naphtho [2,3-d]furan-11-one F 1.94 457.0 A7-1 1113 GT13- 14 [01128] 3-(4-Hydroxy-butoxy)- 6,6-dimethyl-8- ((2R,3R)-2,3,4- trihydroxy-butoxy)- 6H-benzo[b]naphtho [2,3-d]furan-11-one F 2.01 471.0 A7-1 1114 GT13- 15 [01129] 3-Isopropoxy- 6,6-dimethyl-8- ((2R,3R)-2,3,4- trihydroxy-butoxy)- 6H-benzo[b]naphtho [2,3-d]furan-11-one H 5.40 441.0 A7-1 1115 GT13- 16 [01130] 3-(2-Methoxy-ethoxy)- 6,6-dimethyl-8- ((2R,3R)-2,3,4- trihydroxy-butoxy)- 6H-benzo[b] naphtho[2,3-d] furan-11-one F 2.17 457.0 A7-1 1116 GT13- 17 [01131] 3-(3-Methoxy-propoxy)- 6,6-dimethyl-8- ((2R,3R)-2,3,4- trihydroxy-butoxy)- 6H-benzo[b]naphtho [2,3-d]furan-11-one F 2.34 471.0 A7-1 1117 GT13- 18 [01132] 3-(4-Methoxy-butoxy)- 6,6-dimethyl-8- ((2R,3R)-2,3,4- trihydroxy-butoxy)- 6H-benzo[b]naphtho [2,3-d]furan-11-one F 2.45 485.0 A7-1 1118 GT13- 19 [01133] 3-((S)-2,3-Dihydroxy- propoxy)-6,6-dimethyl- 8-((2R,3R)-2,3,4- trihydroxy-butoxy)- 6H-benzo[b]naphtho [2,3-d]furan-11-one F 1.69 473.0 A7-1- A7-14- 1 1119 GT13- 20 [01134] 3-((R)-2,3-Dihydroxy- propoxy)-6,6-dimethyl- 8-((2R,3R)-2,3,4- trihydroxy-butoxy)- 6H-benzo[b]naphtho [2,3-d]furan-11-one F 1.69 473.0 A7-1- A7-14- 1

[4253] The compounds described in the following Table 37 were prepared from Compound GT13-7 according to carbamation that is used for the preparation of Compound A9-1.

TABLE-US-00037 TABLE 37 Exam- Reten- ple Comp. HPLC tion Me- No. No. Structure Compound Name Condition Time m/z thod 1120 GT13- 21 [01135] (4-Methoxy-phenyl)- carbamic acid 6,6- dimethyl-11-oxo-8- ((2R,3R)-2,3,4- trihydroxy-butoxy)- 6,11-dihydro- benzo[b]naphtho [2,3-d]furan-3-yl ester B 4.34 548.2 A9-1 1121 GT13- 22 [01136] (3-Methoxy-phenyl)- carbamic acid 6,6- dimethyl-11-oxo-8- ((2R,3R)-2,3,4- trihydroxy-butoxy)- 6,11-dihydro- benzo[b]naphtho [2,3-d]furan-3-yl ester B 4.69 548.2 A9-1 1122 GT13- 23 [01137] (2-Methoxy-phenyl)- carbamic acid 6,6- dimethyl-11-oxo-8- ((2R,3R)-2,3,4- trihydroxy-butoxy)- 6,11-dihydro- benzo[b]naphtho [2,3-d]furan-3-yl ester B 4.99 548.3 A9-1 1123 GT13- 24 [01138] Phenyl-carbamic acid 6,6-dimethyl-11- oxo-8-((2R,3R)-2,3,4- trihydroxy- butoxy)-6,11-dihydro- benzo[b]naphtho [2,3-d]furan-3-yl ester B 4.67 518.2 A9-1 1124 GT13- 25 [01139] Cyclohexyl- carbamic acid 6,6-dimethyl-11- oxo-8-((2R,3R)-2,3,4- trihydroxy-butoxy)- 6,11-dihydro- benzo[b]naphtho [2,3-d]furan-3-yl ester B 4.94 524.2 A9-1 1125 GT13- 26 [01140] Benzyl-carbamic acid 6,6-dimethyl-H-oxo-8- ((2R,3R)-2,3,4- trihydroxy-butoxy)- 6,11-dihydro- benzo[b]naphtho [2,3-d]furan-3-yl ester A 2.09 532.3 A9-1 1126 GT13- 27 [01141] Methyl-phenyl- carbamic acid 6,6- dimethyl-11-oxo-8- ((2R,3R)-2,3,4- trihydroxy-butoxy)- 6,11-dihydro- benzo[b]naphtho [2,3-d]furan-3-yl ester B 4.88 532.3 A9-1

[4254] The compounds described in the following Table 38 were prepared from corresponding intermediates by alkylation and carbamation based on the method described in the Table.

TABLE-US-00038 TABLE 38 Exam- Reten- ple Comp. HPLC tion Me- No. No. Structure Compound Name Condition Time m/z thod 1127 GT13- 28 [01142] 3-(2-Diethylamino- ethoxy)-8-methoxy- 6,6-dimethyl-6H- benzo[b] naphtho[2,3-d] furan-11-one H 4.65 408.0 A7-17 1128 GT13- 29 [01143] 2-[8-((R)-2,3- Dihydroxy- propoxy)-6,6- dimethyl-11-oxo- 6,11-dihydro- benzo[b] naphtho[2,3-d] furan-3-yloxy]- N-phenyl-acetamide B 4.70 502.0 A7-17 A8-1 T13-3 1129 GT13- 30 [01144] (4-tert- Butyl-phenyl)- carbamic acid 8- ((R)-2,3-dihydroxy- propoxy)-6,6- dimethyl-11-oxo- 6,11-dihydro- benzo[b] naphtho[2,3-d] furan-3-yl ester B 6.19 544.3 A9-1 1130 GT13- 31 [01145] (2-tert- Butyl-phenyl)- carbamic acid 8- ((R)-2,3-dihydroxy- propoxy)- 6,6-dimethyl- 11-oxo-6,11- dihydro-benzo[b] naphtho[2,3-d] furan-3-yl ester B 5.74 544.3 A9-1 1131 GT13- 32 [01146] (5-tert-Butyl-2- methoxy-phenyl)- carbamic acid 8- ((R)-2,3-dihydroxy- propoxy)-6,6- dimethyl-11-oxo- 6,11-dihydro- benzo[b] naphtho[2,3-d] furan-3-yl ester B 6.52 574.3 A9-1 1132 GT13- 33 [01147] 6,6-Dimethyl-3- (pyrimidin- 2-yloxy)-8- ((2R,3R)-2,3,4- trihydroxy- butoxy)-6H- benzo[b] naphtho[2,3-d] furan-11-one H 4.14 477.0 A7-17

Example 1133

Compound GT14-1

3-Chloro-8-((R)-2,3-dihydroxy-propoxy)-6,6-dimethyl-5,6-dihydro-benzo[f]pyrido[4,3-b]indol-11-one

[4255] ##STR01148##

[4256] Compound BZ2-2 was demethylated according to the method used for the preparation of Compound A6, and subsequently introduced with a substituent group and deprotected according to the method used for the preparation of Compound A7-14-1 and A7-14-2.

[4257] LCMS: m/z 386 [M+H].sup.+

[4258] HPLC retention time: 3.02 min (analysis condition B)

Example 1134

Compound GT15-1

2-Iodo-3-(4-methoxy-benzyloxy)-pyridine

[4259] ##STR01149##

[4260] 2-Iodo-pyridin-3-ol (50 mg, 0.226 mmol), K.sub.2CO.sub.3 (62 mg, 0.452 mmol) and DMF (2 ml) were added with para-methoxybenzyl chloride (46 L, 0.339 mmol), and the mixture was stirred overnight at 45 C. The resultant was added with water, and then extracted with ethyl acetate. The organic layer was washed with saturated brine, and the resulting residues obtained after concentration under reduced pressure were purified by silica gel column (ethyl acetate/hexane) to obtain the title compound (21 mg, 27%).

[4261] LCMS: m/z 342 [M+H].sup.+

[4262] HPLC retention time: 3.44 min (analysis condition Y)

Example 1135

Compound GT15-2

7-Methoxy-3-[3-(4-methoxy-benzyloxy)-pyridin-2-yl]-1,1-dimethyl-3,4-dihydro-1H-naphthalen-2-one

[4263] ##STR01150##

[4264] Toluene (0.5 ml) was added to 7-methoxy-1,1-dimethyl-3,4-dihydro-1H-naphthalen-2-one (Compound A2, 36 mg), 2-iodo-3-(4-methoxy-benzyloxy)-pyridine (Compound GT15-1, 50 mg), sodium t-butoxide (35.3 mg), Pd.sub.2dba.sub.3 (13.5 mg) and Xantphos (17 mg), and the mixture was stirred and heated at 80 C. for 2.5 hrs under nitrogen atmosphere. After cooling, the reaction mixture was diluted with ethyl acetate and subjected to Celite filtration. The organic layer was washed with saturated aqueous solution of sodium bicarbonate and saturated brine, and then concentrated under reduced pressure. The resulting residues were purified by silica gel column (ethyl acetate/hexane) to obtain the title compound (27 mg, 44%).

[4265] LCMS: m/z 419 [M+H].sup.+

[4266] HPLC retention time: 3.31 min (analysis condition Y)

Example 1136

Compound GT15-3

8-Methoxy-10,10-dimethyl-5,10-dihydro-11-oxa-4-aza-benzo[b]fluorene

[4267] ##STR01151##

[4268] To the mixture of 7-methoxy-3-[3-(4-methoxy-benzyloxy)-pyridin-2-yl]-1,1-dimethyl-3,4-dihydro-1H-naphthalen-2-one (Compound GT15-2, 21 mg) and ethyl acetate (0.8 ml), sulfuric acid (0.2 ml) was added. The mixture was stirred and heated at 70 C. for 5 hrs. After cooling, the reaction mixture was neutralized with 2 N aqueous solution of sodium hydroxide. The mixture was diluted with ethyl acetate. The organic layer was washed with saturated aqueous solution of sodium bicarbonate and saturated brine, and then concentrated under reduced pressure. The resulting residues were purified by silica gel column (ethyl acetate/hexane) to obtain the title compound (7 mg, 50%).

[4269] LCMS: m/z 280 [M+H].sup.+

[4270] HPLC retention time: 2.71 min (analysis condition Y)

Example 1137

Compound GT15-4

8-Methoxy-10,10-dimethyl-10H-11-oxa-4-aza-benzo[b]fluoren-5-one

[4271] ##STR01152##

[4272] 8-Methoxy-10,10-dimethyl-5,10-dihydro-11-oxa-4-aza-benzo[b]fluorene (Compound GT15-3, 22 mg) was dissolved in MeCN (0.26 ml) and water (0.13 ml), added with sodium chlorite (14 mg) and N-hydroxyphthalimide (2.6 mg), and the mixture was stirred at 40 C. for 1 hr. The reaction mixture was diluted with ethyl acetate. The organic layer was washed with saturated aqueous solution of sodium bicarbonate and saturated brine, and then concentrated under reduced pressure. The resulting residues were purified by silica gel column (ethyl acetate/hexane) to obtain the title compound (16 mg, 70%).

[4273] LCMS: m/z 294 [M+H].sup.+

[4274] HPLC retention time: 2.85 min (analysis condition Y)

Example 1138

Compound GT15-5

8-Hydroxy-10,10-dimethyl-10H-11-oxa-4-aza-benzo[b]fluoren-5-one

[4275] ##STR01153##

[4276] Mixture of 8-methoxy-10,10-dimethyl-10H-11-oxa-4-aza-benzo[b]fluoren-5-one (Compound GT15-4, 25 mg) and pyridine hydrochloric acid salt (492 mg) was stirred and heated at 178 C. overnight. The reaction mixture was cooled, and added with water. The mixture was neutralized with saturated aqueous solution of sodium bicarbonate and extracted with DCM. The organic layer was washed with saturated brine, and then concentrated under reduced pressure. The resulting residues were purified by silica gel column (DCM/MeOH) to obtain the title compound (13 mg, 54%).

[4277] LCMS: m/z 280 [M+H].sup.+

[4278] HPLC retention time: 2.30 min (analysis condition Y)

Example 1139

Compound GT15-6

8-[(4R,5R)-5-(Tert-butyl-dimethyl-silanyloxymethyl)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy]-10,10-dimethyl-10H-11-oxa-4-aza-benzo[b]fluoren-5-one

[4279] ##STR01154##

[4280] In the same manner as Compound A7-1, the title compound was synthesized from Compound GT15-5 and Compound T22-0 (29 mg, 50%).

[4281] LCMS: m/z 538 [M+H].sup.+

[4282] HPLC retention time: 3.64 min (analysis condition Y)

Example 1140

Compound GT15-7

10,10-Dimethyl-8-((2R,3R)-2,3,4-trihydroxy-butoxy)-10H-11-oxa-4-aza-benzo[b]fluoren-5-one

[4283] ##STR01155##

[4284] To the mixture of 8-[(4R,5R)-5-(tert-butyl-dimethyl-silanyloxymethyl)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy]-10,10-dimethyl-10H-11-oxa-4-aza-benzo[b]fluoren-5-one (Compound GT15-6, 27 mg), MeOH (0.1 ml) and THF (0.3 ml), 0.5 N sulfuric acid (0.1 ml) was added, and the mixture was stirred and heated at 55 to 60 C. for 4 hrs. The reaction mixture was neutralized with saturated aqueous solution of sodium bicarbonate. The resulting solid was filtered and washed with diethyl ether. The filtrate was extracted with the mixture solution of DCM and MeOH (DCM:MeOH=10:1). The organic layer was washed with saturated brine, and dried over magnesium sulfate. The filtered solid and the residues obtained after concentration under reduced pressure were combined and purified by silica gel column (DCM/MeOH) to obtain the title compound (5.4 mg, 28%).

[4285] LCMS: m/z 384 [M+H].sup.+

[4286] HPLC retention time: 2.02 min (analysis condition Y)

Example 1141

Compound GT15-8

7-Methoxy-3-(3-methoxymethoxy-pyridin-4-yl)-1,1-dimethyl-3,4-dihydro-1H-naphthalen-2-one

[4287] ##STR01156##

[4288] To 7-methoxy-1,1-dimethyl-3,4-dihydro-1H-naphthalen-2-one (Compound A2, 924 mg), 4-iodo-3-methoxymethoxy-pyridine (1 g), sodium t-butoxide (906 mg), Pd.sub.2dba.sub.3 (173 mg) and S-Phos (185 mg), toluene (19 ml) was added, and the mixture was stirred and heated at 70 C. for 2 hrs under nitrogen atmosphere. The reaction mixture was diluted with ethyl acetate and filtered through Celite. The organic layer was washed with saturated aqueous solution of sodium bicarbonate and saturated brine, and then concentrated under reduced pressure. The resulting residues were purified by silica gel column (ethyl acetate/hexane) to obtain the title compound (610 mg, 47%).

[4289] LCMS: m/z 342 [M+H].sup.+

[4290] HPLC retention time: 2.60 min (analysis condition Y)

Example 1142

Compound GT15-9

3-(3-Hydroxy-pyridin-4-yl)-7-methoxy-1,1-dimethyl-3,4-dihydro-1H-naphthalen-2-one

[4291] ##STR01157##

[4292] Mixture of 7-methoxy-3-(3-methoxymethoxy-pyridin-4-yl)-1,1-dimethyl-3,4-dihydro-1H-naphthalen-2-one (Compound GT15-8, 430 mg) and 4 N hydrochloric acid dioxane solution (5 ml) was heated and stirred at room temperature for 1.5 hrs. The reaction mixture was neutralized with 2 N aqueous solution of sodium hydroxide. The resulting mixture was extracted with the mixture of DCM and MeOH (DCM:MeOH=9:1). The residues obtained after concentration under reduced pressure were purified by silica gel column (DCM/MeOH) to obtain the title compound (280 mg, 75%).

[4293] LCMS: m/z 298 [M+H].sup.+

[4294] HPLC retention time: 2.41 min (analysis condition Y)

Example 1143

Compound GT15-10

8-Methoxy-10,10-dimethyl-5,10-dihydro-11-oxa-2-aza-benzo[b]fluorene

[4295] ##STR01158##

[4296] Mixture of 3-(3-hydroxy-pyridin-4-yl)-7-methoxy-1,1-dimethyl-3,4-dihydro-1H-naphthalen-2-one (Compound GT15-9, 270 mg) and methanesulfonic acid (1 ml) was stirred and heated at 110 C. for 0.5 hrs. After cooling, the reaction mixture was neutralized with 2 N aqueous solution of sodium hydroxide. The resulting mixture was extracted with the mixture of DCM and MeOH (DCM:MeOH=9:1). The organic layer was concentrated under reduced pressure, and the resulting residues were purified by silica gel column (DCM/MeOH) to obtain the title compound (110 mg, 43%).

[4297] LCMS: m/z 280 [M+H].sup.+

[4298] HPLC retention time: 2.53 min (analysis condition Y)

Example 1144

Compound GT15-11

8-Methoxy-10,10-dimethyl-10OH-11-oxa-2-aza-benzo[b]fluoren-5-one

[4299] ##STR01159##

[4300] 8-Methoxy-10,10-dimethyl-5,10-dihydro-11-oxa-2-aza-benzo[b]fluorene (Compound GT15-10, 20 mg) was dissolved in acetonitrile (0.2 ml) and water (0.15 ml), added with sodium chlorite (16 mg) and N-hydroxyphthalimide (2.3 mg), and the mixture was stirred at 40 C. for 40 min. To the reaction mixture, ethyl acetate was added. The organic layer was washed with saturated aqueous solution of sodium bicarbonate and saturated brine, and then concentrated under reduced pressure. The resulting residues were purified by silica gel column (ethyl acetate/hexane) to obtain the title compound (12 mg, 57%).

[4301] LCMS: m/z 294 [M+H].sup.+

[4302] HPLC retention time: 2.51 min (analysis condition Y)

Example 1145

Compound GT15-12

8-Hydroxy-10,10-dimethyl-10H-11-oxa-2-aza-benzo[b]fluoren-5-one

[4303] ##STR01160##

[4304] DCM (0.34 ml) solution of 8-methoxy-10,10-dimethyl-10H-11-oxa-2-aza-benzo[b]fluoren-5-one (Compound GT15-11, 10 mg) was cooled to 78 C., added with the DCM solution (0.17 ml) of 1.0 M BBr.sub.3, and the mixture was stirred at room temperature overnight. To the reaction mixture, water and saturated aqueous solution of sodium bicarbonate were added, and the solid produced therefrom was filtered off. The filtrate was extracted with the mixture solution of DCM and MeOH (DCM:MeOH=9:1). The organic layer was washed with saturated brine. The filtered solid and the residues obtained after concentration under reduced pressure were combined to obtain the title compound (9.5 mg, 99%).

[4305] LCMS: m/z 280 [M+H].sup.+

[4306] HPLC retention time: 2.50 min (analysis condition Y)

Example 1146

Compound GT15-13

8-[(4R,5R)-5-(Tert-butyl-dimethyl-silanyloxymethyl)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy]-10,10-dimethyl-10H-11-oxa-2-aza-benzo[b]fluoren-5-one

[4307] ##STR01161##

[4308] Under the same conditions as the method for synthesizing Compound A7-1, the title compound was prepared from Compound GT15-12 and Compound T22-0 (38 mg, 66%).

[4309] LCMS: m/z 538 [M+H].sup.+

[4310] HPLC retention time: 3.55 min (analysis condition Y)

Example 1147

Compound GT15-14

10,10-Dimethyl-8-((2R,3R)-2,3,4-trihydroxy-butoxy)-10H-11-oxa-2-aza-benzo[b]fluoren-5-one

[4311] ##STR01162##

[4312] Under the same conditions as the method for synthesizing Compound GT15-7, the title compound was prepared from Compound GT15-13 (2.1 mg, 84%).

[4313] LCMS: m/z 384 [M+H].sup.+

[4314] HPLC retention time: 1.70 min (analysis condition Y)

Example 1148

Compound GT15-15

3-Bromo-2-(4-methoxy-benzyloxy)-pyridine

[4315] ##STR01163##

[4316] Under the same conditions as the method for synthesizing Compound G15-1, the title compound was prepared from 3-bromo-pyridin-2-ol (740 mg, 88%).

[4317] LCMS: m/z 295 [M+H].sup.+

[4318] HPLC retention time: 2.86 min (analysis condition Y)

Example 1149

Compound GT15-16

7-Methoxy-3-[2-(4-methoxy-benzyloxy)-pyridin-3-yl]-1,1-dimethyl-3,4-dihydro-1H-naphthalen-2-one

[4319] ##STR01164##

[4320] To 7-methoxy-1,1-dimethyl-3,4-dihydro-1H-naphthalen-2-one (Compound A2, 845 mg), 3-bromo-2-(4-methoxy-benzyloxy)-pyridine (Compound GT15-15, 1.46 g), sodium t-butoxide (597 mg), palladium acetate (18.6 mg) and tri-tert-butylphosphine tetrafluoroboric acid (21 mg), toluene (10 ml) and THF (2 ml) were added and the mixture was stirred and heated at 90 C. for 2.5 hrs under nitrogen atmosphere. After cooling, the reaction mixture was added with saturated aqueous solution of ammonium chloride, and then extracted with ethyl acetate. The organic layer was washed with saturated brine, and the residues obtained after concentration under reduced pressure were purified by silica gel column (ethyl acetate/hexane) to obtain the title compound (140 mg, 8%).

[4321] LCMS: m/z 419 [M+H].sup.+

[4322] HPLC retention time: 3.50 min (analysis condition Y)

Example 1150

Compound GT15-17

8-Methoxy-10,10-dimethyl-10H-11-oxa-1-aza-benzo[b] fluoren-5-one

[4323] ##STR01165##

[4324] Under the same conditions as the method for synthesizing Compound GT15-3, the title compound was prepared from Compound GT15-16 (49 mg, 52%).

[4325] LCMS: m/z 294 [M+H].sup.+

[4326] HPLC retention time: 3.39 min (analysis condition Y)

Example 1151

Compound GT15-18

8-Hydroxy-10,10-dimethyl-10 OH-11-oxa-1-aza-benzo[b]fluoren-5-one

[4327] ##STR01166##

[4328] Under the same conditions as the method for synthesizing Compound GT15-5, the title compound was prepared from Compound GT15-17 (6.5 mg, 51%).

[4329] LCMS: m/z 280 [M+H].sup.+

[4330] HPLC retention time: 3.10 min (analysis condition Y)

Example 1152

Compound GT15-19

8-[(4R,5R)-5-(Tert-butyl-dimethyl-silanyloxymethyl)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy]-10,10-dimethyl-10H-11-oxa-1-aza-benzo[b]fluoren-5-one

[4331] ##STR01167##

[4332] Under the same conditions as the method for synthesizing Compound A7-1, the title compound was prepared from Compound GT15-18 and Compound T22-0 (4.5 mg, 11%).

[4333] LCMS: m/z 538 [M+H].sup.+

[4334] HPLC retention time: 3.88 min (analysis condition Y)

Example 1153

Compound GT15-20

10,10-Dimethyl-8-((2R,3R)-2,3,4-trihydroxy-butoxy)-10H-11-oxa-1-aza-benzo[b]fluoren-5-one

[4335] ##STR01168##

[4336] Under the same conditions as the method for synthesizing Compound GT15-7, the title compound was prepared from Compound GT15-19 (7.9 mg, 51%).

[4337] LCMS: m/z 384 [M+H].sup.+

[4338] HPLC retention time: 2.57 min (analysis condition Y)

Example 1154

Compound GT15-21

8-Methoxy-10,10-dimethyl-5,10-dihydro-11-oxa-3-aza-benzo[b]fluorene

[4339] ##STR01169##

[4340] To 7-methoxy-1,1-dimethyl-3,4-dihydro-1H-naphthalen-2-one (Compound A2, 2.5 g), 3-bromo-4-chloro-pyridine (2 g), sodium t-butoxide (3 g), Pd.sub.2dba.sub.3 (476 mg), and S-Phos (512 mg), toluene (20 ml) was added, and the mixture was stirred and heated at 100 C. overnight under nitrogen atmosphere. After cooling, the reaction mixture was diluted with ethyl acetate and filtered through Celite. The organic layer was washed with saturated aqueous solution of sodium bicarbonate and saturated brine. Thereafter, the organic layer was dried over sodium sulfate. The residues obtained after concentration under reduced pressure were purified by silica gel column (ethyl acetate/hexane) to obtain the title compound (112 mg, 4%).

[4341] LCMS: m/z 280 [M+H].sup.+

[4342] HPLC retention time: 2.46 min (analysis condition Y)

Example 1155

Compound GT15-22

8-Methoxy-10,10-dimethyl-10H-11-oxa-3-aza-benzo[b] fluoren-5-one

[4343] ##STR01170##

[4344] Under the same conditions as the method for synthesizing Compound GT15-3, the title compound was prepared from Compound GT15-21 (49 mg, 52%).

[4345] LCMS: m/z 294 [M+H].sup.+

[4346] HPLC retention time: 2.30 min (analysis condition Y)

Example 1156

Compound GT15-23

8-Hydroxy-10,10-dimethyl-10H-11-oxa-3-aza-benzo[b]fluoren-5-one

[4347] ##STR01171##

[4348] Under the same conditions as the method for synthesizing Compound GT15-12, the title compound was prepared from Compound GT15-22 (110 mg, 77%).

[4349] LCMS: m/z 280 [M+H].sup.+

[4350] HPLC retention time: 1.95 min (analysis condition Y)

Example 1157

Compound GT15-24

8-[(4R,5R)-5-(Tert-butyl-dimethyl-silanyloxymethyl)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy]-10,10-dimethyl-10H-11-oxa-3-aza-benzo[b]fluoren-5-one

[4351] ##STR01172##

[4352] Under the same conditions as the method for synthesizing Compound A7-1, the title compound was prepared from Compound GT15-23 and Compound T22-0 (38 mg, 49%).

[4353] LCMS: m/z 538 [M+H].sup.+

[4354] HPLC retention time: 3.40 min (analysis condition Y)

Example 1158

Compound GT15-25

10,10-Dimethyl-8-((2R,3R)-2,3,4-trihydroxy-butoxy)-10H-11-oxa-3-aza-benzo[b]fluoren-5-one

[4355] ##STR01173##

[4356] Under the same conditions as the method for synthesizing Compound GT15-7, the title compound was prepared from Compound GT15-24 (17 mg, 72%).

[4357] LCMS: m/z 384 [M+H].sup.+

[4358] HPLC retention time: 1.48 min (analysis condition Y)

Example 1159

Compound GT16-1

2-(2-Bromo-4-methoxy-phenyl)-propan-2-ol

[4359] ##STR01174##

[4360] To the mixture of 1-(2-bromo-4-methoxyphenyl)-ethanone (300 mg) dissolved in THF solution (3 ml), MeMgBr (3 M THF solution, 0.52 ml) was added at 0 C. under nitrogen atmosphere. Then, the mixture was stirred at room temperature for 6 hrs. The reaction mixture was added with saturated aqueous solution of ammonium chloride and extracted with ethyl acetate. The organic layer was washed with saturated brine, and the residues obtained after concentration under reduced pressure were purified by silica gel column (ethyl acetate/hexane) to obtain the title compound (220 mg, 69%).

[4361] .sup.1H-NMR (CDCL.sub.3) : 7.55 (1H, d), 7.14 (1H, d), 6.83 (1H, dd), 3.79 (3H, s), 2.72 (1H, s), 1.73 (6H, s)

Example 1160

Compound GT16-2

2-[1-(2-Bromo-4-methoxyphenyl)-1-methylethyl]benzofuran

[4362] ##STR01175##

[4363] Mixture comprising 2-(2-bromo-4-methoxyphenyl)-propan-2-ol (100 mg), 2,3-benzofuran (0.19 ml) and polyphosphoric acid (1 g) was stirred and heated at 90 C. for 30 min. The reaction mixture was added with water and extracted with DCM. The residues obtained after concentration under reduced pressure were purified by silica gel column (DCM/hexane) to obtain the title compound (143 mg, 51%).

[4364] .sup.1H-NMR (CDCL.sub.3) : 7.4-7.5 (1H, m), 7.3-7.4 (2H, m), 7.1-7.25 (3H, m), 6.87 (1H, dd), 6.42 (1H, s) 3.79 (3H, s), 1.84 (6H, s)

Example 1161

Compound GT16-3

2-(1-Benzofuran-2-yl-1-methyl-ethyl)-5-methoxy-benzoic Acid

[4365] ##STR01176##

[4366] To the mixture comprising 2-[1-(2-bromo-4-methoxyphenyl)-1-methylethyl]benzofuran (140 mg) and THF (2 ml), n-butyl lithium (2.5 M solution, 0.17 ml) was added at 78 C. under nitrogen atmosphere. The mixture was stirred for 20 min. The resulting reaction mixture was flushed with carbon dioxide gas for 15 min. Then, the reaction mixture was added with saturated aqueous solution of ammonium chloride and extracted with ethyl acetate. The organic layer was washed with water and saturated brine, and the residues obtained after concentration under reduced pressure were purified by silica gel column (DCM/MeOH) to obtain the title compound (68 mg, 54%).

[4367] LCMS: m/z 311 [M+H].sup.+

[4368] HPLC retention time: 2.92 min (analysis condition Y)

Example 1162

Compound GT16-4

9-Methoxy-6,6-dimethyl-6H-benzo[b]naphtho[2,3-d] furan-11-one

[4369] ##STR01177##

[4370] To the DCM solution (1 ml) of 2-(1-benzofuran-2-yl-1-methylethyl)-5-methoxy benzoic acid (63 mg), trifluoroacetic anhydride (0.03 ml) was added at room temperature under nitrogen atmosphere. The mixture was stirred for 30 min. The reaction mixture was then added with water and extracted with DCM. The organic layer was dried over sodium sulfate. The residues obtained after concentration under reduced pressure were purified by silica gel column (DCM) to obtain the title compound (50 mg, 84%).

[4371] LCMS: m/z 293 [M+H].sup.+

[4372] HPLC retention time: 3.49 min (analysis condition Y)

Example 1163

Compound GT16-5

9-Hydroxy-6,6-dimethyl-6H-benzo[b]naphtho[2,3-d]furan-11-one

[4373] ##STR01178##

[4374] Under the same conditions as the method for synthesizing Compound A6, the title compound was prepared from Compound GT16-4.

[4375] LCMS: m/z 279 [M+H].sup.+

[4376] HPLC retention time: 3.05 min (analysis condition Y)

Example 1164

Compound GT16-6

9-(2-Diethylamino-ethoxy)-6,6-dimethyl-6H-benzo[b]naphtho[2,3-d] furan-11-one

[4377] ##STR01179##

[4378] Under the same conditions as the method for synthesizing Compound A7-17, the title compound was prepared from Compound GT16-5.

[4379] LCMS: m/z 378 [M+H].sup.+

[4380] HPLC retention time: 2.41 min (analysis condition Y)

Example 1165

Compound GT16-7

9-((S)-2,2-Dimethyl-[1,3]dioxolan-4-yl methoxy)-6,6-dimethyl-6H-benzo[b]naphtho[2,3-d]furan-11-one

[4381] ##STR01180##

[4382] Under the same conditions as the method for synthesizing Compound A7-17, the title compound was prepared from Compound GT16-5 and toluene-4-sulfonic acid (R)-2,2-dimethyl-[1,3]dioxolan-4-yl methyl ester.

[4383] LCMS: m/z 393 [M+H].sup.+

[4384] HPLC retention time: 3.22 min (analysis condition Y)

Example 1166

Compound GT16-8

9-((R)-2,3-Dihydroxy-propoxy)-6,6-dimethyl-6H-benzo[b]naphtho[2,3-d]furan-11-one

[4385] ##STR01181##

[4386] Under the same conditions as the method for synthesizing Compound A7-14-2, the title compound was prepared from Compound GT16-7.

[4387] LCMS: m/z 353 [M+H].sup.+

[4388] HPLC retention time: 2.83 min (analysis condition Y)

Example 1167

Compound GT16-9

3-(6,6-Dimethyl-11-oxo-6,11-dihydro-benzo[b]naphtho[2,3-d]furan-9-yl)-benzoic Acid

[4389] ##STR01182##

[4390] In the same manner as Compound GT9-2, the title compound was synthesized from Compound GT16-5.

[4391] LCMS: m/z 383 [M+H].sup.+

[4392] HPLC retention time: 7.11 min (analysis condition H)

Example 1168

Compound GT16-10

9-(4-Hydroxymethyl-phenyl)-6,6-dimethyl-6H-benzo[b]naphtho[2,3-d]furan-11-one

[4393] ##STR01183##

[4394] In the same manner as Compound GT9-2, the title compound was synthesized from Compound GT16-5.

[4395] LCMS: m/z 369 [M+H].sup.+

[4396] HPLC retention time: 6.97 min (analysis condition H)

[4397] The compounds described in the following Table 39 were synthesized according to the method shown below. Specifically, Compound GT17-1 was prepared from 8-methoxy-1,1-dimethyl-3,4-dihydro-1H naphthalen-2-one and bromophenol by following the method that is used for the preparation of Compound Z10, Z11 and Z12. Compound GT17-1 was demethylated according to the method used for the preparation of Compound A6, and as a result 7-hydroxy-6,6-dimethyl-6H-benzo[b]naphtho[2,3-d]furan-11-one was prepared. The resulting hydroxy compound was subjected to the alkylation according to the method used for the preparation of A7-1, or Mitsunobu reaction used for the preparation of Compound A7-17 for introducing a corresponding side chain or a synthetic equivalent thereof. Thereafter, if necessary, functional group modification was carried out to prepare Compound GT17-2 and Compound GT17-3.

TABLE-US-00039 TABLE 39 Example Comp. HPLC Retention No. No. Structure Compound Name Condition Time m/z 1169 GT17-1 [01184] 7-Methoxy-6,6-dimethyl-6H- benzo[b]naphtho[2,3-d] furan-11-one Y 13.42 293.0 1170 GT17-2 [01185] 7-(2-Diethylamino-ethoxy)-6,6- dimethyl-6H-benzo[b]naphtho [2,3-d]furan-11-one Y 9.92 378.0 1171 GT17-3 [01186] 7-((R)-2,3-Dihydroxy-propoxy)- 6,6-dimethyl-6H- benzo[b]naphtho[2,3-d] furan-11-one Y 11.68 353.0

[4398] The compounds described in the following Table 40 were synthesized according to the method shown below.

[4399] By using the method used for the preparation of Compound Z10, Z11 and Z12, Compound GT18-1 was prepared from Compound M1 and bromophenol. Further, according to the method used for the preparation of Compound A6, Compound GT18-1 was demethyalted to prepare 8-hydroxy-11H-spiro[benzo[b]naphtho[2,3-d]furan-6,1-cyclopentan]-11-one, which was then introduced with a side chain based on the alkylation that is used for the preparation of Compound A7-1. As a result, Compound GT18-2 was prepared.

[4400] The following spiro compounds were prepared from 7-methoxy-3,4-dihydro-1H-naphthalen-2-one and corresponding dibromide in the same manner as above.

TABLE-US-00040 TABLE 40 Example Comp. HPLC Retention No. No. Structure Compound Name Condition Time m/z 1172 GT18-1 [01187] 8-methoxy-11H- spiro[benzo[b]naptho [2,3-d]furan-6,1- cyclopentane]-11-one Y 10.00 319.0 1173 GT18-2 [01188] 8-(2-diethylamino-ethoxy)- 11H-spiro[benzo[b]naptho [2,3-d]furan-6,1- cyclopentane]-11-one C 2.19 404.0 1174 GT18-3 [01189] 8-(2-diethylamino-ethoxy)- 11H-spiro[benzo[b] naptho[2,3-d]furan-6,1- cyclohexane]-11-one C 3.28 418.2 1175 GT18-4 [01190] 8-((2R, 3R)-2, 3, 4- trihydroxybutoxy)-11H- spiro[benzo[b]naptho [2,3-d]furan-6,1- cyclohexane]-11-one A 2.26 423.2 1176 GT18-5 [01191] 8-methoxy-11H- spiro[benzo[b] naptho[2,3-d]furan-6,1- cyclobutane]-11-one Y 9.00 305.0 1177 GT18-6 [01192] 8-(2-diethylamino-ethoxy)- 2,3,5,6-tetrahydro-11H- spiro[benzo[b]naptho[2,3-d] furan-6,4-pyran]-11-one B 4.05 420.3

Example 1178

Compound GT19-1

8-(2-Diethylamino-ethoxy)-6,6-dimethyl-3-phenyl-6H-benzo[b]naphtho[2,3-d]furan-11-one

[4401] ##STR01193##

[4402] According to the method described before, the preparation was carried out by using 7-methoxy-1,1-dimethyl-3,4-dihydro-1H naphthalen-2-one and 2-bromo-5-trifluorophenol.

[4403] LCMS: m/z 446 [M+H].sup.+

[4404] HPLC retention time: 3.25 min (analysis condition C)

Example 1179

Compound GT19-2

8-(2-Diethylamino-ethoxy)-6,6-dimethyl-3-phenyl-6H-benzo[b]naphtho[2,3-d]furan-11-one

[4405] ##STR01194##

[4406] By carrying out Suzuki coupling of Compound GT23-5 and a corresponding boronic acid reagent based on the method that is used for the preparation of Compound GT9-2, the title compound was prepared.

[4407] LCMS: m/z 454 [M+H].sup.+

[4408] HPLC retention time: 2.67 min (analysis condition F)

Example 1180

Compound GT20-1

8-Hydroxy-6,6-dimethyl-3-(2-phenyl-ethanesulfonyl)-5,6-dihydro-benzo[b]carbazol-11-one

[4409] ##STR01195##

[4410] 3-Bromo-8-hydroxy-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one (72.2 mg, 0.203 mmol), 2-phenylethanethiol (0.0297 ml, 0.221 mmol), Pd.sub.2dba.sub.3 (9.3 mg, 0.0102 mmol), Xantphos (11.6 mg, 0.020 mmol) and ethyl diisopropylamine (0.068 ml, 0.40 mmol) were dissolved in dioxane (0.6 ml), and the mixture was stirred at 110 C. for 16 hrs under nitrogen atmosphere. Water and ethyl acetate were added to the mixture to give a suspension, which was then filtered. The organic layer was washed with water and saturated brine, and then concentrated under reduced pressure. The resulting residues were purified by silica gel column (ethyl acetate/hexane). The resulting residues were dissolved in THF (4 ml), and the supernatant liquid (2 ml) was taken and added with water (1 ml) and OXONE (99 mg). The resulting mixture was stirred at room temperature overnight. The reaction solution was partitioned between water and ethyl acetate. The organic layer was washed with brine, and then concentrated under reduced pressure. The resulting residues were purified by silica gel column (ethyl acetate/hexane) to obtain the title compound (37.1 mg).

[4411] LCMS: m/z 446 [M+H].sup.+

[4412] HPLC retention time: 2.51 min (analysis condition F)

Example 1181

Compound GT20-2

6,6-Dimethyl-3-(2-phenyl-ethanesulfonyl)-8-((2R,3R)-2,3,4-trihydroxy-butoxy)-5,6-dihydro-benzo[b]carbazol-11-one and Compound GT20-3

8-Isopropoxy-6,6-dimethyl-3-(2-phenyl-ethanesulfonyl)-5,6-dihydro-benzo[b]carbazol-11-one

[4413] ##STR01196##

[4414] 8-Hydroxy-6,6-dimethyl-3-(2-phenyl-ethanesulfonyl)-5,6-dihydro-benzo[b]carbazol-11-one (30 mg, 0.0673 mmol), [(4R,5R)-5-(tert-butyl-dimethyl-silanyloxymethyl)-2,2-dimethyl-[1,3]dioxolan-4-yl]methanol (22.3 mg, 0.0808 mmol), and PPh.sub.3 (23 mg, 0.0875 mmol) were dissolved in THF (0.5 ml), added with DIAD (0.0169 ml, 0.0808 mmol), and the mixture was stirred at 50 C. overnight. After cooling, the reaction solution was filtered and concentrated under reduced pressure. The resulting residues were purified by silica gel column (ethyl acetate/hexane). The resulting residues were dissolved in THF (0.4 ml) and water (0.13 ml), added with camphor sulfonic acid (28.1 mg, 0.121 mmol), and then subjected to microwave irradiation at 80 C. for 15 min under nitrogen atmosphere. Ethyl acetate was added to the resultant. The organic layer was washed with saturated aqueous solution of sodium hydrocarbonate and saturated brine, and then concentrated under reduced pressure. The resulting residues were purified by thin layer chromatography (MeOH/DCM) to obtain Compound GT20-2 (10.5 mg) and Compound GT20-3 (2.4 mg).

Compound GT20-2

[4415] LCMS: m/z 550 [M+H].sup.+

[4416] HPLC retention time: 2.20 min (analysis condition F)

Compound GT20-3

[4417] LCMS: m/z 488 [M+H].sup.+

[4418] HPLC retention time: 3.13 min (analysis condition F)

Example 1182

Compound GT20-4

3-Methanesulfonyl-6,6-dimethyl-8-((2R,3R)-2,3,4-trihydroxy-butoxy)-5,6-dihydro-benzo[b]carbazol-11-one

[4419] ##STR01197##

[4420] The DMA solution (0.6 ml) comprising Compound GT23-2 (59.6 mg, 0.167 mmol), sodium methanethiolate (77 mg, 1.10 mmol), Pd.sub.2dba.sub.3 (23.7 mg, 0.0259 mmol) and Xantphos (29.7 mg, 0.0513 mmol) was subjected to microwave irradiation at 180 C. for 30 min under nitrogen atmosphere. The reaction solution was partitioned between aqueous solution of potassium dihydrophosphoric acid and ethyl acetate. The organic layer was washed with saturated brine, and then concentrated under reduced pressure. The resulting residues were purified by silica gel column (ethyl acetate/hexane and MeOH/DCM). The resulting solids were dissolved in THF (1 ml) and water (0.5 ml), and then added with OXONE (101.4 mg). The resulting mixture was stirred at room temperature for 2 hrs. The reaction solution was partitioned between water and ethyl acetate. The organic layer was washed with saturated brine, and then concentrated under reduced pressure. The resulting residues were suspended and washed with MTBE. The resulting solid was dissolved in THF (0.4 ml), and added with PPh.sub.3 (37 mg, 0.141 mmol), [(4R,5R)-5-(tert-butyl-dimethyl-silanyloxymethyl)-2,2-dimethyl-[1,3]dioxolan-4-yl]-methanol (39.0 mg, 0.141 mmol) and DEAD (2.2 M toluene solution, 0.064 ml, 0.141 mmol), and the mixture was stirred at 40 C. for 4 hrs under nitrogen atmosphere. The reaction solution was partitioned between water and ethyl acetate. The organic layer was washed with saturated brine, and then concentrated under reduced pressure. The resulting residues were purified by silica gel column (MeOH/DCM). Thus-obtained product was dissolved in THF (0.25 ml) and MeOH (0.05 ml), added with 0.5 M sulfuric acid (0.1 ml), and the mixture was stirred at 60 C. for 5 hrs. After cooling, the mixture was added with diethyl ether and sodium hydrocarbonate (13 mg, 0.15 mmol). The separated aqueous layer was filtered, concentrated under reduced pressure, and suspended and purified with MeOH to obtain the title compound as a white solid (10.4 mg, 14%).

[4421] LCMS: m/z 460 [M+H].sup.+

[4422] HPLC retention time: 1.71 min (analysis condition F)

Example 1183

Compound GT20-5

8-((R)-2,3-Dihydroxy-propoxy)-6,6-dimethyl-3-methylsulfanyl-5,6-dihydro-benzo[b]carbazol-11-one

[4423] ##STR01198##

[4424] 3-Bromo-8-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy)-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one (47.3 mg, 0.101 mmol), sodium methanethiolate (34.6 mg, 0.493 mmol), Pd.sub.2(dba).sub.3 (13.1 mg, 0.0413 mmol), and Xantphos (17.9 mg, 0.0309 mmol) were dissolved in DMA (0.5 ml) and subjected to microwave irradiation at 200 C. for 30 min under nitrogen atmosphere. The resultant was partitioned between aqueous solution of potassium dihydrophosphoric acid and ethyl acetate. The organic layer was washed with saturated brine, and then concentrated under reduced pressure. The resulting residues were purified by thin layer chromatography (ethyl acetate/DCM). The resulting solid was dissolved in THF (0.23 ml) and MeOH (0.06 ml), and then added with 0.5 M sulfuric acid (0.12 ml). The resulting mixture was stirred at 60 C. for 2 hrs. The reaction solution was diluted with diethyl ether and neutralized with sodium hydrocarbonate (15.5 mg, 0.185 mmol). Thereafter, the solution was partitioned between brine and ethyl acetate. The organic layer was concentrated under reduced pressure. The resulting residues were added with diethyl ether. The precipitated solid was filtered to obtain the title compound as a white solid (15.8 mg, 39%).

[4425] LCMS: m/z 398 [M+H].sup.+

[4426] HPLC retention time: 4.46 min (analysis condition H)

Example 1184

Compound GT20-5

8-((R)-2,3-Dihydroxy-propoxy)-6,6-dimethyl-3-thiazol-2-yl-5,6-dihydro-benzo[b]carbazol-11-one

[4427] ##STR01199##

[4428] 3-Bromo-8-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy)-6,6-dimethyl-5,6-dihydrobenzo[b]carbazol-11-one (47 mg, 0.10 mmol), bis (pinacolate)diborone (33 mg, 0.13 mmol), Pd (dppf).sub.2Cl.sub.2.DCM (8.2 mg, 0.010 mmol) and potassium acetate (294 mg, 0.3 mmol) were dissolved in dioxane (0.6 ml), and the mixture was stirred at 100 C. overnight under nitrogen atmosphere. The resultant was partitioned between aqueous solution of potassium dihydrophosphoric acid and ethyl acetate. The organic layer was washed with saturated brine, and then concentrated under reduced pressure. The resulting residues were purified by silica gel column (ethyl acetate/DCM) to obtain 8-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy)-6,6-dimethyl-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-5,6-dihydro-benzo[b]carbazol-11-one (30.2 mg). The product (11 mg) was dissolved in DMA (0.4 ml), added with 2-bromothiazole (0.0038 ml, 0.0428 mmol), Pd (PPh.sub.3).sub.4 (5.3 mg, 0.00459 mmol), potassium phosphate (27.4 mg, 0.129 mmol) and water (0.1 ml), and the mixture was subjected to microwave irradiation at 140 C. for 7 min under nitrogen atmosphere. The resultant was partitioned between aqueous solution of potassium dihydrophosphoric acid and ethyl acetate. The organic layer was washed with saturated brine, and then concentrated under reduced pressure. The resulting residues were purified by thin layer chromatography (MeOH/DCM). The resulting solid was dissolved in MeOH (1 ml), and then added with 1 N HCl (3 drops). The resulting mixture was stirred at 60 C. for 2 hrs. The reaction solution was concentrated under reduced pressure, and the residues obtained therefrom were suspended and washed with DCM/hexane (2/1) followed by drying to obtain the title compound as a yellow solid (8.7 mg).

[4429] LCMS: m/z 435 [M+H].sup.+

[4430] HPLC retention time: 1.76 min (analysis condition A)

[4431] The compounds described in the following Table 41 were also synthesized in the same manner.

TABLE-US-00041 TABLE 41 Example Comp. HPLC Retention No. No. Structure Compound Name Condition Time m/z 1185 GT20-6 [01200] 8-((R)-2,3-Dihydroxy-propoxy)- 3-(1-methoxymethyl- 1H-imidazol-2-yl)-6,6- dimethyl-5,6-dihydro- benzo[b]carbazol-11-one B 2.63 462.0 1186 GT20-7 [01201] 8-((R)-2,3-Dihydroxy- propoxy)-3-(1H-imidazol-2-yl)- 6,6-dimethyl-5,6-dihydro- benzo[b]carbazol-11-one B 2.45 418.5

Example 1187

Compound GT20-8

8-((R)-2,3-Dihydroxy-propoxy)-3-methoxymethyl-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one and Compound GT20-9

8-((R)-2,3-Dihydroxy-propoxy)-3-hydroxymethyl-6,6-dimethyl-5,6-dihydro-benzo[b]carbazol-11-one

[4432] ##STR01202##

[4433] 3-Bromo-8-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy)-6,6-dimethyl-5,6-dihydrobenzo[b]carbazol-11-one (200.2 mg, 0.426 mmol), palladium acetate (II) (19 mg, 0.0848 mmol), hexacarbonyl molybdenum (115.5 mg, 0.438 mmol) and tris(o-tolyl)phosphine (52.5 mg, 0.172 mmol) were dissolved in THF (1.3 ml) and ethanol (0.075 ml), added with DBU (0.195 ml), and subjected to microwave irradiation at 160 C. for 15 min under nitrogen atmosphere. The resulting reaction solution was partitioned between aqueous solution of potassium dihydrophosphoric acid and ethyl acetate. The organic layer was washed with saturated brine, and then concentrated under reduced pressure. The resulting residues were dissolved in ethanol (10 ml) and THF (3 ml), added with 2 N KOH (2 ml), and stirred at room temperature for 2 hrs, at 50 C. overnight and at 70 C. for 2 hrs. The reaction solution was partitioned between aqueous solution of potassium dihydrophosphoric acid and ethyl acetate. The organic layer was washed with saturated brine, and then concentrated under reduced pressure. The resulting residues were suspended and purified with MTBE/hexane (1/1) (155.4 mg). The THF solution (1.5 ml) of the product (109 mg) was added with TEA (0.052 ml, 0.373 mmol) and ethyl chloroformate (0.029 ml, 0.303 mmol) under ice cooling, and the mixture was stirred at 0 C. for 2 hrs. Subsequently, ethanol (1 ml) and sodium borohydride (75.7 mg, 2.0 mmol) were added to the mixture, which was then stirred at room temperature for 2 hrs. The reaction solution was partitioned between aqueous solution of potassium dihydrophosphoric acid and ethyl acetate. The organic layer was washed with saturated brine, and then concentrated under reduced pressure. The resulting residues were purified by silica gel column (MeOH/DCM) (35.2 mg). Thus-obtained solid (9.6 mg) was dissolved in MeOH (1 ml), added with 1 N HCl (3 drops), and the mixture was stirred at 60 C. for 90 min. After cooling and concentration under reduced pressure, the resultant was purified by TLC (MeOH/DCM) to obtain Compound GT20-8 (6.2 mg, white solid) and Compound GT20-9 (4.3 mg, white solid).

Compound GT20-8

[4434] LCMS: m/z 396 [M+H].sup.+

[4435] HPLC retention time: 1.66 min (analysis condition A)

Compound GT20-9

[4436] LCMS: m/z 382 [M+H].sup.+

[4437] HPLC retention time: 1.37 min (analysis condition A)

Example 1188

Compound GT21-1

8-[(E)-2-(2,2-Dimethyl-[1,3]dioxolan-4-yl)-vinyl]-6,6-dimethyl-6H-benzo[b]naphtho[2,3-d]furan-11-one

[4438] ##STR01203##

[4439] To the DMF solution (4 ml) of trifluoro-methanesulfonic acid 6,6-dimethyl-11-oxo-6,11-dihydro-benzo[b]naphtho[2,3-d]furan-8-yl ester (300 mg), 2,2-dimethyl-4-vinyl-[1,3]dioxolane (469 mg) and PdCl.sub.2(PPh.sub.3).sub.2 (103 mg), sodium hydrocarbonate (184 mg) was added, and the mixture was stirred at 100 C. overnight under nitrogen atmosphere. The reaction mixture was diluted with ethyl acetate. The organic layer was washed with saturated aqueous solution of sodium bicarbonate and saturated brine, and then concentrated under reduced pressure. The resulting residues were purified by silica gel column (ethyl acetate/hexane) to obtain the title compound (130 mg, 46%).

[4440] LCMS: m/z 389 [M+H].sup.+

[4441] HPLC retention time: 3.28 min (analysis condition Y)

Example 1189

Compound GT21-2

8-(3,4-Dihydroxy-butyl)-6,6-dimethyl-6H-benzo[b]naphtho[2,3-d]furan-11-one

[4442] ##STR01204##

[4443] To the MeOH solution (5 ml) of 8-[(E)-2-(2,2-dimethyl-[1,3]dioxolan-4-yl)-vinyl]-6,6-dimethyl-6H-benzo[b]naphtho[2,3-d]furan-11-one (125 mg), 10% Pd-C (25 mg) was added and the mixture was stirred overnight at room temperature under hydrogen atmosphere. The catalyst was removed by filtration. The residues obtained after concentration under reduced pressure were purified by HPLC to obtain the title compound (35 mg, 31%).

[4444] LCMS: m/z 351 [M+H].sup.+

[4445] HPLC retention time: 1.79 min (analysis condition Y)

Example 1190

Compound GT21-3

8-Amino-6,6-dimethyl-6H-benzo[b]naphtho[2,3-d] furan-11-one

[4446] ##STR01205##

[4447] To trifluoro-methanesulfonic acid 6,6-dimethyl-11-oxo-6,11-dihydro-benzo[b]naphtho[2,3-d]furan-8-yl ester (100 mg), benzhydrylideneamine (0.05 ml), cesium carbonate (110 mg), palladium acetate (2 mg) and BINAP (7 mg), THF (2 ml) was added. The mixture was stirred and heated at 65 C. overnight under nitrogen atmosphere, and the reaction mixture was diluted with ethyl acetate. The organic layer was washed with saturated aqueous solution of sodium bicarbonate and saturated brine, and then concentrated under reduced pressure. The resulting residues were purified by silica gel column (ethyl acetate/hexane) to obtain the title compound (16 mg, 23%).

[4448] LCMS: m/z 278 [M+H].sup.+

[4449] HPLC retention time: 2.52 min (analysis condition Y)

Example 1191

Compound GT21-4

8-[((S)-2,2-Dimethyl-[1,3]dioxolan-4-yl methyl)-amino]-6,6-dimethyl-6H-benzo[b]naphtho[2,3-d]furan-11-one

[4450] ##STR01206##

[4451] The mixture comprising 8-amino-6,6-dimethyl-6H-benzo[b]naphtho[2,3-d]furan-11-one (50 mg), (R)-4-iodomethyl-2,2-dimethyl-[1,3]dioxolane (104 mg), potassium carbonate (150 mg) and DMF (2 ml) was stirred and heated at 160 C. for 2 days under nitrogen atmosphere. The reaction mixture was diluted with ethyl acetate. The organic layer was washed with water and saturated brine, and then concentrated under reduced pressure. The resulting residues were purified by silica gel column (ethyl acetate/hexane). To the compound (71 mg) obtained therefrom, THF (1 ml) and conc. hydrochloric acid (8 drops) were added and the mixture was stirred at room temperature for 1 hr. The reaction mixture was added with saturated aqueous solution of sodium bicarbonate and then diluted with ethyl acetate. The organic layer was washed with saturated aqueous solution of sodium bicarbonate and saturated brine, and then concentrated under reduced pressure. The resulting residues were purified by silica gel column (ethyl acetate/hexane) to obtain the title compound (34 mg, 51%).

[4452] LCMS: m/z 392 [M+H].sup.+

[4453] HPLC retention time: 3.11 min (analysis condition Y)

Example 1192

Compound GT21-5

8-((S)-2,3-Dihydroxy-propylamino)-6,6-dimethyl-6H-benzo[b]naphtho[2,3-d] furan-11-one

[4454] ##STR01207##

[4455] In the same manner as Compound A7-14-2, Compound GT21-4 was deprotected to obtain the title compound.

[4456] LCMS: m/z 352 [M+H].sup.+

[4457] HPLC retention time: 2.26 min (analysis condition Y)

Example 1193

Compound GT22-1

8-(2-Diethylamino-ethoxy)-6,6-dimethyl-3-propyl-6H-benzo[b]naphtho[2,3-d]furan-11-one

[4458] ##STR01208##

[4459] To the mixture of trifluoro-methanesulfonic acid 8-(2-diethylamino-ethoxy)-6,6-dimethyl-11-oxo-6,11-dihydro-benzo[b]naphtho[2,3-d]furan-3-yl ester (15 mg), which had been obtained in the same manner as Compound A7-25, tris(1-methyl-3-oxo-1-butenyloxy) iron (III) (1 mg), NMP (0.3 ml) and THF (0.3 ml), n-PrMgBr (0.88 M, THF solution, 0.291 ml) and zinc chloride (0.5 M THF solution, 0.114 ml) were added at 0 C. under nitrogen atmosphere, and the mixture was stirred at 0 C. for 10 min. The reaction mixture was added with water and extracted with ethyl acetate. The organic layer was washed with saturated brine, and then concentrated under reduced pressure. The resulting residues were purified by silica gel column (ethyl acetate/hexane) to obtain the title compound (4.5 mg, 38%).

[4460] LCMS: m/z 420 [M+H].sup.+

[4461] HPLC retention time: 5.77 min (analysis condition H)

Example 1194

Compound GT22-2

8-(2-Diethylamino-ethoxy)-3-ethyl-6,6-dimethyl-6H-benzo[b]naphtho[2,3-d]furan-11-one

[4462] ##STR01209##

[4463] In the same manner as Compound GT22-2, the title compound was synthesized.

[4464] LCMS: m/z 406 [M+H].sup.+

[4465] HPLC retention time: 5.12 min (analysis condition B)

Example 1195

Compound GT23-1

3-Bromo-8-methoxy-6,6-dimethyl-6H-benzo[b]naphtho[2,3-d] furan-11-one

[4466] ##STR01210##

[4467] 8-Methoxy-6,6-dimethyl-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-6H-benzo[b]naphtho[2,3-d]furan-11-one (10.3 mg), which had been synthesized from Compound Z12 under the same conditions as the method for synthesizing Compound GT20-5, was mixed with copper (II) bromide (16.5 mg), MeOH (0.5 ml) and water (0.25 ml), and the mixture was stirred and heated at 70 C. for 2 hrs. DCM was added to the reaction solution for extraction. The organic layer was concentrated and purified by silica gel column to obtain the title compound (9.4 mg).

[4468] LCMS: m/z 371 [M+H].sup.+

[4469] HPLC retention time: 7.55 min (analysis condition B)

Example 1196

Compound GT23-2

3-Bromo-8-hydroxy-6,6-dimethyl-6H-benzo[b]naphtho[2,3-d]furan-11-one

[4470] ##STR01211##

[4471] In the same manner as Compound GT15-5, 3-bromo-8-methoxy-6,6-dimethyl-6H-benzo[b]naphtho[2,3-d]furan-11-one was deprotected to obtain the title compound.

[4472] LCMS: m/z 357 [M+H].sup.+

[4473] HPLC retention time: 2.82 min (analysis condition A)

[4474] The compounds described in the following Table 42 were synthesized from Compound GT23-2 according to the method given in the Table.

TABLE-US-00042 TABLE 42 Example Comp. HPLC Retention No. No. Structure Compound Name Condition Time m/z Method 1197 GT23-3 [01212] 3-Bromo-6,6-dimethyl- 8-((2R,3R)-2,3,4- trihydroxy-butoxy)-6H- benzo[b]naphtho[2,3-d] furan-11-one D 2.30 461.0 T22-1- 1 T22-2 1198 GT23-4 [01213] 3-Bromo-8-((R)-2,3- dihydroxy-propoxy)- 6,6-dimethyl-6H- benzo[b]naphtho [2,3-d]furan-11-one A 5.42 431.0 A7-14- 1 A7-14- 2 1199 GT23-5 [01214] 3-Bromo-8- (2-diethylamino- ethoxy)-6,6- dimethyl-6H- benzo[b] naphtho[2,3-d] furan-11-one H 5.37 456.0 A7-17

Example 1200

Compound GT24-1

8-((R)-2,3-Dihydroxy-propoxy)-3-iodo-6,6-dimethyl-6H-benzo[b]naphtho[2,3-d]furan-11-one

[4475] ##STR01215##

[4476] To 3-bromo-8-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy)-6,6-dimethyl-6H-benzo[b]naphtho[2,3-d]furan-11-one (15 mg, 0.032 mmol), CuI (6.2 mg, 0.032 mmol), NaI (9.6 mg, 0.064 mmol) and trans-N,N-dimethylcyclohexane-1,2-diamine (0.01 ml) were added and the mixture was stirred for 48 hrs under nitrogen atmosphere. The reaction solution was diluted with ethyl acetate. The organic layer was washed with saturated brine, and then concentrated under reduced pressure. The resulting residues were purified by silica gel column (ethyl acetate/hexane) to obtain 8-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy)-3-iodo-6,6-dimethyl-6H-benzo[b]naphtho[2,3-d]furan-11-one (16 mg, 97%), which was then deprotected according to the method of A-14-2 to give the title compound.

[4477] LCMS: m/z 479 [M+H].sup.+

[4478] HPLC retention time: 4.26 min (analysis condition A)

Example 1201

Compound GT24-2

3-Iodo-6,6-dimethyl-8-((2R,3R)-2,3,4-trihydroxy-butoxy)-6H-benzo[b]naphtho[2,3-d]furan-11-one

[4479] ##STR01216##

[4480] In the same manner as Compound GT24-1, 3-iodo-8-[(4R,5R)-5-(tert-butyl-dimethyl-silanyloxymethyl)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy]-6,6-dimethyl-6H-benzo[b]naphtho[2,3-d]furan-11-one was synthesized from 3-bromo-8-[(4R,5R)-5-(tert-butyl-dimethyl-silanyloxymethyl)-2,2-dimethyl-[1,3]dioxolan-4-yl methoxy]-6,6-dimethyl-6H-benzo[b]naphtho[2,3-d]furan-11-one. Subsequently, according to the same method as Compound T22-2, deprotection was carried out to obtain the title compound.

Example 1202

Compound GT25-1

6,6-Dimethyl-8-(4-methyl-piperazine-1-sulfonyl)-6H-benzo[b]naphtho[2,3-d]furan-11-one

[4481] ##STR01217##

[4482] By using the method for preparing Compound B1, trifluoro-methanesulfonic acid 6,6-dimethyl-11-oxo-6,11-dihydro-benzo[b]naphtho[2,3-d]furan-8-yl ester was prepared from 8-hydroxy-6,6-dimethyl-6H-benzo[b]naphtho[2,3-d]furan-11-one. This trifluoromethanesulfonic acid ester (205 mg), (2R)-1-[(1R)-1-[bis (1,1-dimethylethyl)phosphino] ethyl]-2-(dicyclohexylphosphino)ferrocene (13 mg), palladium acetate (6 mg), 2-trimethylsilanyl-ethanethiol (90 L) and potassium carbonate (85 mg) were reacted in DME to obtain a product (120 mg). To the benzyl alcohol solution (90 L) of the product (50 mg), DCM solution of N-chlorosuccinimide (90 mg) was added, and the mixture was stirred at room temperature. The reaction solution was partitioned between water and ethyl acetate, and the organic layer was concentrated under reduced pressure. To the DCM solution of thus-obtained white solid, N-methylpiperazine (10 L) was added and the mixture was stirred. The residues obtained after removing the solvent by distillation were purified by TLC to obtain the title compound as a white solid (6 mg).

Example 1203

Compound GT26-1

(2-Bromo-5-methoxy-phenyl)-acetonitrile

[4483] ##STR01218##

[4484] To the THF solution (1000 ml) of 2-bromo-5-methoxy-benzoic acid methyl ester (20 g, 81.6 mmol), the THF suspension (50 ml) of LAH (4.07 g, 102 mmol) was added under ice cooling. The mixture was stirred for 30 min under ice cooling. The reaction solution was partitioned between saturated aqueous solution of Na.sub.2SO.sub.4 and ethyl acetate. The organic layer was washed with saturated brine and concentrated under reduced pressure. The resulting residues were dissolved in DCM (200 ml), and added with TEA (12.51 ml, 89.76 mmol) and MsCl (6.63 ml, 85.68 mmol) under ice cooling, followed by stirring overnight at room temperature. The reaction mixture was diluted with DCM, and washed in order with 10% aqueous solution of citric acid, saturated aqueous solution of NaHCO.sub.3and saturated brine. The residues obtained after concentration under reduced pressure were dissolved in DMF (100 ml), and added with the DMF (500 ml) solution of NaCN (40 g, 81.6 mmol) under ice cooling. After stirring for 2 hrs under ice cooling, the reaction mixture was extracted with ether, washed with saturated brine and dried over magnesium sulfate. The residues obtained after concentration under reduced pressure were purified by silica gel column (hexane:ethyl acetate=10:1) to obtain the title compound (12.1 g, 67%).

[4485] .sup.1H-NMR (400 MHz, CDCl.sub.3) 3.82 (s, 3H), 6.77 (d, 1H), 7.07 (s, 1H), 7.47 (d, 1H)

Example 1204

1-(2-Bromo-5-methoxy-phenyl)-cyclopropane carbonitrile

Compound GT26-2

[4486] ##STR01219##

[4487] 2-Bromo-5-methoxy-phenyl)-acetonitrile (12.2 g, 53.97 mmol) was dissolved in toluene (50 ml), and added with tetrabutylammonium bromide (3.55 g, 10.79 mmol), dibromoethane (7.05 ml, 80.95 mmol) and 50% aqueous solution of NaOH (50 ml) at room temperature. The mixture was stirred at room temperature for 4 hrs. The reaction mixture was added with water and extracted with ethyl acetate. The residues obtained after concentration under reduced pressure were purified by silica gel column (hexane:ethyl acetate) to obtain the title compound (11.18 g, 82%).

[4488] .sup.1H-NMR (400 MHz, CDCl.sub.3) 1.33 (t, 1H), 1.76 (t, 1H), 3.79 (s, 3H), 6.75-6.79 (m, 1H), 6.89 (d, 1H), 7.47 (d, 1H)

Example 1205

1-(2-Bromo-5-methoxy-phenyl)-cyclopropane carboxylic acid

Compound GT26-3

[4489] ##STR01220##

[4490] 1-(2-Bromo-5-methoxy-phenyl)-cyclopropane carbonitrile (3.0 g, 11.9 mmol) was dissolved in ethylene glycol (30 ml). After adding KOH (2.1 g, 33.3 mmol) thereto, the mixture was stirred and heated at 180 C. for 7 hrs. After cooling, the reaction mixture was added with 1 N HCl (90 ml). The reaction mixture was extracted with ether, washed with water and saturated brine and dried over magnesium sulfate. After concentration under reduced pressure, the title compound was obtained (12.3 g, 72%).

[4491] LCMS: m/z 272 [M+H].sup.+

[4492] HPLC retention time: 2.03 min (analysis condition Y)

Example 1206

Compound GT26-4

2-[1-(2-Bromo-5-methoxy-phenyl)-cyclopropyl]-benzofuran

[4493] ##STR01221##

[4494] To the DCM solution (6 ml) of 1-(2-bromo-5-methoxy-phenyl)-cyclopropane carboxylic acid (0.3 g, 1.1 mmol), DMF (2 drops) and oxalyl chloride (0.23 ml, 2.5 mmol) were added at room temperature, and the mixture was stirred at room temperature for 2 hrs. The residues obtained from the reaction solution after concentration under reduced pressure were dissolved in toluene (6 ml), added with (2-hydroxybenzyl)triphenylphosphonium bromide (0.605 g, 1.32 mmol) and TEA (0.46 ml, 3.3 mmol), and the resulting mixture was stirred and heated at 100 C. overnight. The residues obtained after concentration under reduced pressure were purified by silica gel column (hexane:DCM) to obtain the title compound (0.309 g, 81%).

[4495] LCMS: m/z 343 [M+H].sup.+

[4496] HPLC retention time: 3.55 min (analysis condition Y)

Example 1207

Compound GT26-5

2-(1-Benzofuran-2-yl-cyclopropyl)-4-methoxy-benzoic Acid

[4497] ##STR01222##

[4498] To the THF solution (3 ml) of 2-[1-(2-bromo-5-methoxy-phenyl)-cyclopropyl]-benzofuran (0.259 g, 0.75 mmol), n-BuLi was added at 78 C., and the mixture was stirred at 78 C. for 20 min. Thereafter, the mixture was flushed with carbon dioxide gas. The reaction mixture was added with saturated solution of NH.sub.4Cl and extracted with ethyl acetate. The residues obtained after concentration under reduced pressure were purified by silica gel column (DCM:MeOH) to obtain the title compound (0.163 g, 70%).

[4499] LCMS: m/z 309 [M+H].sup.+

[4500] HPLC retention time: 2.67 min (analysis condition Y)

Example 1208

Compound GT26-6

8-Methoxy-11H-spiro[benzo[d]naphtho[2,3-b]furan-6,1-cyclopropan]-11-one

[4501] ##STR01223##

[4502] To the DCM solution (10 ml) of 2-(1-benzofuran-2-yl-cyclopropyl)-4-methoxy-benzoic acid (1.0 g, 3.24 mmol), trifluoroacetic acid anhydride (0.45 ml, 3.24 mmol) was added at 78 C., and the mixture was stirred at 78 C. for 10 min, at 50 C. for 10 min, and at 30 C. for 20 min. Thereafter, the mixture was added with water and extracted with DCM. The residues obtained after concentration under reduced pressure were washed with DCM and hexane to obtain the title compound (0.163 g, 70%).

[4503] LCMS: m/z 291 [M+H].sup.+

[4504] HPLC retention time: 2.90 min (analysis condition Y)

Example 1209

Compound GT26-7

8-(2-(Diethylamino)ethoxy)-11H-spiro[benzo[d]naphtho[2,3-b] furan-6,1-cyclopropan]-11-one

[4505] ##STR01224##

[4506] In the same manner as Compound A6 and Compound A7-17, the title compound was obtained from 8-methoxy-11H-spiro[benzo[d]naphtho[2,3-b]furan-6,1-cyclopropan]-11-one.

[4507] LCMS: m/z 376 [M+H].sup.+

[4508] HPLC retention time: 1.65 min (analysis condition Y)

Example 1210

Compound GT27-1

2-(2-Bromo-5-methoxy-phenyl)-2-ethyl-butyric Acid

[4509] ##STR01225##

[4510] (2-Bromo-5-methoxy-phenyl)-acetic acid methyl ester (3.51 g, 13.5 mmol) was dissolved in DMF (4.5 ml), and added with NaH (2.1 g, 67.7 mmol). Subsequently, 15-crown-5 (1.38 ml, 6.8 mmol) and EtI (5.5 ml, 67.7 mmol) cooled to 0 C. were added to the mixture. The mixture was diluted with ethyl acetate and washed with water and saturated brine. The residues obtained after concentration under reduced pressure were purified by silica gel column (hexane-ethyl acetate). Then, the resultant was dissolved in ethanol (80 ml) and water (80 ml), added with KOH (91 g), and stirred at 140 C. The reaction solution was extracted with ethyl acetate, and washed with water and saturated brine. After concentration under reduced pressure, the target compound was obtained (10.62 g, 78%).

[4511] LCMS: m/z 301 [M+H].sup.+

[4512] HPLC retention time: 3.07 min (analysis condition Y)

Example 1211

Compound GT27-2

2-(2-Bromo-5-methoxy-phenyl)-2-ethyl-butyric Acid o-Tolyl Ester

[4513] ##STR01226##

[4514] Compound GT27-1 (0.5 g, 1.66 mmol) was dissolved in DCM (10 ml), added with DMF (2 drops) and oxalyl chloride (0.28 ml, 3.32 mmol), and the mixture was stirred for 2 hrs. The reaction mixture obtained after concentration under reduced pressure was dissolved in toluene (5 ml), added with DMAP (406 mg, 3.32 mmol), and the mixture was heated under reflux. The reaction mixture was extracted with ethyl acetate, washed with 1 N HCl, and saturated brine. The residues obtained after concentration under reduced pressure were purified by silica gel column (hexane-ethyl acetate) to obtain the target compound (0.36 g, 86%).

[4515] LCMS: m/z 393 [M+H].sup.+

[4516] HPLC retention time: 3.03 min (analysis condition Y)

Example 1212

Compound GT27-3

2-(2-Bromo-5-methoxy-phenyl)-2-ethyl-butyric acid 2-[(triphenyl-phosphanyl)-methyl]-phenyl Ester Bromate Salt

[4517] ##STR01227##

[4518] Compound GT27-2 (0.118 g, 0.302 mmol) was dissolved in carbon tetrachloride (3 ml), added with N-bromosuccinimide (54 mg, 0.302 mmol), and the mixture was heated under reflux. The reaction mixture was concentrated under reduced pressure and the resulting residues were purified by silica gel column (ethyl acetate-hexane). The product was dissolved in toluene (3 ml), added with PPh.sub.3 (77 mg, 0.302 mmol), and the mixture was heated under reflux. The reaction mixture was concentrated under reduced pressure to obtain the target compound (130 mg, 57%).

Example 1213

Compound GT27-4

2-[1-(2-Bromo-5-methoxy-phenyl)-1-ethyl-propyl]-benzofuran

[4519] ##STR01228##

[4520] To the toluene solution (3 ml) of Compound GT27-3 (0.14 g, 0.137 mmol), toluene solution (0.16 ml, 0.164 mmol) of 1 M LiHMDS was added. The mixture was heated and stirred for 4 hrs. The reaction mixture was concentrated under reduced pressure and the resulting residues were purified by silica gel column (ethyl acetate:hexane) to obtain the title compound (28 mg, 35%).

[4521] LCMS: m/z 373 [M+H].sup.+

[4522] HPLC retention time: 2.73 min (analysis condition Y)

Example 1214

Compound GT27-5

8-(2-Diethylamino-ethoxy)-6,6-diethyl-6H-benzo[b]naphtho[2,3-d]furan-11-one

[4523] ##STR01229##

[4524] In the same manner as Compound A7-17, the title compound was obtained from Compound GT27-4.

[4525] LCMS: m/z 407 [M+H].sup.+

[4526] HPLC retention time: 1.92 min (analysis condition Y)

Example 1215

Compound GT27-6

8-((R)-2,3-Dihydroxy-propoxy)-6,6-diethyl-6H benzo[b]naphtho[2,3-d] furan-11-one

[4527] ##STR01230##

[4528] In the same manner as Compound A7-14-1 and Compound A7-14-2, the title compound was obtained from Compound GT27-4.

[4529] LCMS: m/z 381 [M+H].sup.+

[4530] HPLC retention time: 2.38 min (analysis condition Y)

[4531] The compounds described in the following Table 43 were synthesized according to the method shown below. According to the method used for the preparation of Compound Z10, Z11 and Z12, 3-chloro-8-methoxy-6H-benzo[b]naphtho[2,3-d]furan-11-one was prepared from Compound A2 and 2-bromo-5-chlorophenol. Subsequently, demethylation was carried out according to the method that is used for the preparation of Compound A6, and thus 3-chloro-8-hydroxy-6H-benzo[b]naphtho[2,3-d]furan-11-one was obtained. Thereafter, according to Mitsunobu reaction that is used for the preparation of Compound A7-1 or the alkylation method that is used for the preparation of A7-17, a corresponding side chain was introduced and, if necessary, functional group modification such as deprotection, etc. was carried out to prepare the compounds listed below.

TABLE-US-00043 TABLE 43 Example Comp. HPLC Retention No. No. Structure Compound Name Condition Time m/z 1216 GT28-1 [01231] 3-Chloro-8-(2-diethylamino-ethoxy)- 6,6-dimethyl-6H-benzo[b]naphtho [2,3-d]furan-11-one F 2.52 412.0 1217 GT28-2 [01232] 3-Chloro-6,6-dimethyl-8-((2R,3R)- 2,3,4-trihydroxy-butoxy)-6H- benzo[b]naphtho[2,3-d]furan-11-one H 5.39 417.0 1218 GT28-3 [01233] 3-Chloro-8-((R)-2,3-dihydroxy- propoxy)-6,6-dimethyl-6H- benzo[b]naphtho[2,3-d]furan-11-one H 5.77 387.0

Pharmacological Testing Method

1. Activity of Inhibiting ALK Enzyme

[4532] ALK-inhibiting activity was measured by following an activity of inhibiting phosphorylation by biotinylated peptide (EGPWLEEEEEAYGWMDF). For the detection of phosphorylation of the biotinylated peptide, time-resolved fluorescence measurement was performed using an anti-phosphorylated tyrosine antibody labeled with europium cryptate and streptavidin conjugated to XL665, i.e., an allophycocyanin derivative. From the inhibition ratio compared to the control group that does not comprise a test compound, 50% inhibitory concentration (i.e., IC.sub.50 value) was calculated.

2. Measurement of an Activity of Inhibiting Karpas-299 Cell Growth

[4533] The test compounds were serially diluted with dimethyl sulfoxide, further diluted with phosphate buffered saline which is free of any Ca.sup.2+, Mg.sup.2+ (50 dilution), and 10 L of the resulting solution was aliquoted in a 96-well plate. Human lymphoma cell line KARPAS-299 was prepared in RPMI-1640 medium to which 10% bovine fetal serum was added to give a cell suspension with the cell density of 10,000 cells/190 L. The resulting cell suspension was aliquoted to the plate (190 L per well) to which the test compound had been already added, and the plate was kept in a 5% carbon dioxide gas incubator at 37 C. Ninety-six hours later, 10 L of WST-8 (manufactured by Dojindo Laboratories) was added to each well, and subsequently the absorbance was measured at 450 nm. From the ratio of inhibition on cell growth which had been obtained from the addition of a test compound compared to the control group with no addition, 50% growth inhibitory concentration (i.e., IC.sub.50 value) of the test compound was calculated. The results are summarized in Tables 44-49.

TABLE-US-00044 TABLE 44 Inhibitory activity ALK-inhibiting on Karpas-299 activity IC.sub.50 cell growth IC.sub.50 Examples (M) (M) 123 (Compound B2-27) 0.00228 0.0138 177 (Compound B4-7) 0.00084 0.0105 178 (Compound B4-8) 0.00153 0.0214 304 (Compound F5-11) 0.00081 0.0061 338 (Compound F5-43) 0.00032 0.0086 341 (Compound F5-46) 0.01056 0.0289 364 (Compound F6-18) 0.00177 0.0231 366 (Compound F6-20) 0.0053 0.0093 372 (Compound G6) 0.03074 0.1682 380 (Compound H6-2) 0.00053 0.0062 429 (Compound J7-10-2) 0.00083 0.0303 543 (Compound O8-5) 0.00032 0.03 550 (Compound O9-7) 0.00090 0.0044 735 (Compound Z7) 0.09385 1.1924 516 (Compound N6-2) 0.003906748 0.0248 725 (Compound X5) 0.687683357 2.8765 882 (Compound AZ7-10) 0.000493765 0.005769 916 (Compound DZ7-1) 0.001836659 0.357381 937 (Compound EZ9-3) 0.006473484 0.056914 939 (Compound EZ9-5) 0.399865279 13.421227 1175 (Compound GT18-4) 0.093 2.012

TABLE-US-00045 TABLE 45 ALK-inhibiting Example activity IC.sub.50 No. Compound (M) 13 A7-1 0.052707597 14 A7-2 0.006159417 38 A7-20 0.026183852 39 A7-21 0.017713716 40 A7-22 0.030434111 41 A7-23 0.029469872 45 A8-2 0.008009528 47 A8-4 0.010253392 51 A8-6-3 0.097920152 52 A8-7 0.045959643 55 A8-10 0.00673264 57 A8-12 0.003594618 63 A8-18 0.016005139 65 A8-20 0.0029 67 A9-1 0.004943 70 A9-3-2 0.007649647 73 A9-6-2 0.001398207 74 A9-7 0.0034607 76 A9-9 0.017148495 78 A9-11 0.051123952 79 A9-12 0.017501168 83 A9-15-2 0.0035 84 A9-16 0.08468 90 B2-1 0.033572 100 B2-9 0.016225317 101 B2-10 0.039433518 102 B2-11 0.072607257 104 B2-13 0.001681324 109 B2-16-3 0.000980809 117 B2-23 0.005436966 118 B2-24 0.014834642 122 B2-26-2 0.007278245 124 B2-28 0.059632226 128 B3-2-2 0.003183521 130 B3-4 0.063798146 135 B3-9 0.01492317 137 B3-11 0.071084446 141 B3-14 0.011893599 142 B3-15 0.030133825 143 B3-16 0.027324427 146 B3-19 0.010369469 147 B3-20 0.026851192 149 B3-22 0.272356381 150 B3-23 0.023088404 151 B3-24 0.003610645 157 B3-27-2 0.002114607 158 B3-28 0.042375341 159 B3-29 0.006002322 165 B3-34 0.006783031 166 B3-35 0.003473067 168 B3-37 0.011859342 179 B4-9 0.002000975 187 CC4-2 0.096115639 189 C1-1 0.051102036 206 C4-9 0.005101172 210 C4-13 0.008752733 212 C4-15 0.009616778 226 D1 0.000991134 227 D2 0.003611773 228 D3-1 0.006279559 245 E4-5 0.009450575 256 E5-2 0.00133756 264 E6-2 0.006668071 265 E6-3 0.008113087 268 F1-3 0.005054399 277 F3-6-2 0.000167996 283 F4-1-1 0.001625048 286 F4-3 0.000951804 290 F4-7 0.001133931 293 F4-10 0.002098847 298 F5-5 0.002385717 300 F5-7 0.002575475 306 F5-13 0.002051837 314 F5-20 0.000996109 319 F5-25 0.000881378 322 F5-28 0.01227125 331 F5-36-2 0.001778367 334 F5-39 0.014824288

TABLE-US-00046 TABLE 46 ALK-inhibiting Example activity IC.sub.50 No. Compound (M) 340 F5-45 0.000579745 346 F5-51 0.002610782 350 F6-4 0.00715425 353 F6-7 0.020276801 355 F6-9 0.001092627 358 F6-12 0.015047658 359 F6-13 0.000399685 389 H9-3 0.002622129 403 I6-4 0.000391036 407 I7-1 0.001863642 421 J7-3 0.015290853 422 J7-4 0.004631153 423 J7-5 0.012009506 424 J7-6 0.001570404 426 J7-8 0.001170682 431 J7-11-2 0.01172814 435 J7-15 0.02319 437 J7-17 0.007091939 438 J8-1 0.012517614 443 J8-6 0.00396 455 JJ5 0.862941682 458 JJ7-2 0.028993627 461 JJ9-1 0.004337558 465 JJ10-1 0.492725332 472 K6 0.029284532 486 K10-5 0.000589765 501 L10-2 0.00160 508 M6-2 0.006136762 517 N6-3 0.03272871 519 N6-5 0.026853329 531 O5-4 0.00431 546 O9-3 0.00086 571 Q8 0.005719259 579 R8-2 0.000769618 591 S4 1.664818863 599 S8-2 0.04064 601 S9-2 0.000456356 607 T2-1 0.432812267 618 T6-1 0.614075453 621 T6-4 0.341433432 628 T11 0.271479209 630 T12-2 0.15422 633 T13-3 0.16211 637 T13-7 0.16821 639 T13-9 0.16189 645 T14-5 0.41327 650 T14-10 0.18923 654 T16-1 0.01951 657 T16-4 0.07941 668 T21 0.8521 671 T22-1-1 0.151061541 678 T22-7 2.8135 679 T22-8 0.583 686 T26-2 0.08320 702 U8-6-2 0.00260 704 U8-7-2 0.00604 706 U8-8-2 0.35976 707 U8-8-3 0.84884 709 U10-1 0.55215 711 U11 0.00193 720 W4-2 0.13445 730 Y5-2 0.554738402 751 K10-10 0.0085 753 K10-12 0.0022 755 K10-14 0.0118 758 K10-17 0.1422 760 K10-19 0.0015 762 L10-3 0.0099 770 L10-11 0.0231 776 B3-42 0.0042 786 E9-4 0.0004 790 E9-8 0.0075 796 F4-11 0.0003 822 PR11-6 0.0003 823 PR11-7 0.0003 824 PR9-9 0.0142 829 PR9-13 0.0007 832 PR11-11 0.0006 846 PR9-25 0.021743738 847 PR11-14 0.001890642

TABLE-US-00047 TABLE 47 ALK-inhibiting Example activity IC.sub.50 No. Compound (M) 849 PR11-16 0.000813047 864 LB5-1 0.424843491 866 LB5-3 2.398295 875 AZ7-3 0.113911239 892 AZ7-20 0.009369855 893 AZ7-21 0.142933634 920 DZ7-5 0.326374265 938 EZ9-4 0.300760062 949 GT2-6 1.3255 956 GT2-13 0.1617 960 GT3-2 5.9473 962 GT3-4 1.0829 963 GT3-5 4.224 967 GT3-9 0.8981 970 GT3-12 1.6214 972 GT4-1 0.29 973 GT4-2 0.104 981 GT5-8 2.9743 982 GT5-9 21.3078 983 GT5-10 3.2 994 GT5-21 1.2466 995 GT6-1 12.9519 996 GT6-2 12.9704 997 GT6-3 0.575 998 GT6-4 4.3855 999 GT6-5 3.9 1000 GT6-6 5.4 1001 GT6-7 3.7 1004 GT6-10 0.9 1005 GT6-11 1.4385 1007 GT6-13 0.7526 1008 GT6-14 4.8429 1013 GT8-3 0.93 1017 GT9-3 0.3785 1019 GT9-5 0.77 1030 GT11-8 5.9346 1031 GT11-9 7.7947 1034 GT11-12 2.076 1035 GT11-13 1.6274 1039 GT11-17 0.7938 1042 GT11-20 0.5083 1043 GT11-21 2.2822 1047 GT11-25 1.9038 1048 GT11-26 5.3708 1050 GT11-28 3.2813 1051 GT11-29 1.811 1052 GT11-30 4.0931 1054 GT11-32 7.0451 1059 GT11-37 2.7739 1060 GT11-38 1.1587 1061 GT11-39 1.0914 1065 GT11-43 3.7028 1066 GT11-44 3.1203 1072 GT11-50 3.3428 1073 GT11-51 2.547 1074 GT11-52 1.2588 1081 GT11-59 1.0586 1083 GT11-61 0.7928 1085 GT11-63 0.9013 1086 GT11-64 0.3127 1087 GT11-65 0.206 1090 GT12-3 0.8541 1096 GT12-9 5.7571 1102 GT13-3 0.4209 1105 GT13-6 0.3894 1113 GT13-14 0.1571 1114 GT13-15 0.7 1117 GT13-18 2.2 1118 GT13-19 0.5 1119 GT13-20 0.42 1125 GT13-26 0.028 1126 GT13-27 3.0645 1127 GT13-28 5.6311 1128 GT13-29 17.4641 1129 GT13-30 0.51 1130 GT13-31 0.54 1164 GT16-5 0.4149 1177 GT18-6 0.7527 1185 GT20-6 1.8

TABLE-US-00048 TABLE 48 Inhibitory activity on Karpas-299 Example cell growth IC.sub.50 No. Compound (M) 15 A7-3 0.1138 17 A7-5 0.6268 19 A7-7 0.3293 21 A7-9 0.2037 22 A7-10 0.3031 25 A7-12 0.1119 46 A8-3 0.0866 56 A8-11 0.0677 58 A8-13 0.0226 60 A8-15 0.2322 61 A8-16 0.0345 62 A8-17 0.1269 64 A8-19 0.0726 66 A8-21 0.1050 68 A9-2 0.1372 72 A9-5 0.0523 93 B2-4 0.0365 138 B3-12 1.4358 154 B3-25-3 0.7298 155 B3-26 1.3613 160 B3-30 0.2282 163 B3-32 0.0652 167 B3-36 0.0390 174 B4-4 0.0812 229 D3-2 0.9700 230 D3-3 0.1320 244 E4-4 0.1090 257 E5-3 0.1895 260 E5-6 0.0527 273 F3-3 0.0162 287 F4-4 0.0071 289 F4-6 0.0291 291 F4-8 0.0221 292 F4-9 0.0650 294 F5-1 0.0091 297 F5-4 0.0018 301 F5-8 0.0297 302 F5-9 0.0043 303 F5-10 0.0135 309 F5-15-2 0.0098 310 F5-16 0.0042 315 F5-21 0.0663 316 F5-22 0.0066 323 F5-29 0.0076 325 F5-31 0.0727 326 F5-32 0.0240 335 F5-40 0.0256 336 F5-41 0.1491 339 F5-44 0.0060 348 F6-2 0.0295 351 F6-5 0.0274 352 F6-6 0.0364 357 F6-11 0.0776 359 F6-13 0.0079 420 J7-2-3 0.0295 434 J7-14 0.5567 446 J9-3 0.0532 467 JJ10-3 6.0632 488 K10-7 0.0518 518 N6-4 0.1224 562 P5 27.7670 605 T1-1 1.8669 636 T13-6 1.2901 640 T13-10 1.3775 642 T14-2 0.6324 646 T14-6 1.9418 649 T14-9 1.08 656 T16-3 2.25 672 T22-1-2 1.7820 680 T23-1 4.2526 681 T23-2 7.0799 688 T27-2 0.9970 689 U5 0.1217 695 U8-3-2 0.6773 698 U8-4-3 1.10 700 U8-5-2 0.3573 708 U9 0.4070 710 U10-2 0.94

TABLE-US-00049 TABLE 49 Inhibitory activity on Karpas-299 Example cell growth IC.sub.50 No. Compound (M) 764 L10-5 0.019 766 L10-7 0.037 767 L10-8 0.024 769 L10-10 0.159 773 B3-40 0.022 787 E9-5 0.041 792 E9-9 0.004 793 PR11-20 0.020313 794 PR11-21 0.06439 827 PR9-11 0.036 839 PR9-20 0.018772 844 PR9-23 0.020492 845 PR9-24 0.067888 850 PR11-17 0.005766 852 PR11-19 0.034632 865 LB5-2 1.287666 878 AZ7-6 1.126471 896 AZ7-24 0.054 935 EZ9-1 16.635 941 W4-4 0.116 976 GT5-3 1.868 979 GT5-6 8.231 980 GT5-7 17.135 984 GT5-11 1.957 985 GT5-12 19.989 986 GT5-13 1.332 987 GT5-14 3.787 990 GT5-17 2.359 991 GT5-18 4.255 993 GT5-20 6.081 1020 GT9-6 2.655 1115 GT13-16 7.875 1123 GT13-24 3.951 1124 GT13-25 5.511 1131 GT13-32 2.501 1132 GT13-33 10.887