NOVEL SMALL MOLECULE INHIBITORS OF TEAD TRANSCRIPTION FACTORS

Abstract

The present disclosure compounds, as well as their compositions and methods of use. The compounds inhibit the activity of the TEAD transcription factor, and are useful in the treatment of diseases related to the activity of TEAD transcription factor including, e.g., cancer and other diseases.

Claims

1. A compound of Formula (I): ##STR01802## or a pharmaceutically acceptable salt thereof, wherein: L.sup.1 is absent, or a group of formula N(R.sup.N) or C(O); D is a group of formula (D1), (D2), (D3), (D4), (D5), (D6) or (D7): ##STR01803## m is 1, 2 or 3; A.sup.1 is C(O)R.sup.1, S(O).sub.2R.sup.1, NHC(O)R.sup.1, (C.sub.1-3 alkylene)-C(O)R.sup.1, NH(C.sub.1-3 alkylene)-C(O)R.sup.1, CN, NO.sub.2, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, (C.sub.1-3 alkylene)-5-10 membered heteroaryl, or (C.sub.1-3 alkylene)-4-10 membered heterocycloalkyl, wherein the (C.sub.1-3 alkylene) group of the (C.sub.1-3 alkylene)-C(O)R.sup.1 group forming A.sup.1 is unsubstituted or substituted by 1, 2, 3, 4 or 5 substituents each independently selected from halogen, OR.sup.a1, NR.sup.c1R.sup.d1, NR.sup.a1(CO)(C.sub.1-6 alkyl), and NR.sup.a1(CO)O(C.sub.1-6 alkyl); and wherein the 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, (C.sub.1-3 alkylene)-5-10 membered heteroaryl, or (C.sub.1-3 alkylene)-4-10 membered heterocycloalkyl forming A.sup.1 is unsubstituted or substituted by 1, 2, 3, 4 or 5 substituents each independently selected from halogen, OR.sup.a1, SR.sup.a1, C(O)OR.sup.a1, NR.sup.c1R.sup.d1, and C(O)NR.sup.c1R.sup.d1; L.sup.2 is absent, or a group of formula N(R.sup.N), O, or C(O); L.sup.3 is absent or a group of formula CH.sub.2, C≡C, N(R.sup.N) or C(O); each R.sup.N is independently H, C.sub.1-6 alkyl, C(O)C.sub.1-6 alkyl, or C(O)OC.sub.1-6 alkyl; R.sup.1 is H, C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, Cy.sup.1A, OH, OC.sub.1-6 alkyl, OCy.sup.1AO(C.sub.1-3 alkylenyl)Cy.sup.1A, NH.sub.2, NHC.sub.1-6 alkyl, N(C.sub.1-6 alkyl).sub.2, NHCy.sup.1A, NH(C.sub.1-3 alkylenyl)Cy.sup.1A, N(C.sub.1-6 alkyl)Cy.sup.1A, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.1A, wherein each of the C.sub.1-6 alkyl forming R.sup.1 is unsubstituted or substituted by 1, 2, 3, 4 or 5 substituents each independently selected from halogen, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1; Cy.sup.1A is C.sub.6-10 aryl, C.sub.3-15 cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkyl, wherein each of the C.sub.6-10 aryl, C.sub.3-15 cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkyl forming Cy.sup.1A is unsubstituted or substituted by 0, 1 or 2 Cy.sup.1B and 0, 1, 2, 3, 4 or 5 substituents each independently selected from unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1 and C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1; each Cy.sup.1B is C.sub.6-10 aryl, C.sub.3-15 cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkyl, wherein each of the C.sub.6-10 aryl, C.sub.3-15 cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkyl forming Cy.sup.1B is unsubstituted or substituted by 1, 2, 3, 4 or 5 substituents each independently selected from unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1; and C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1; A.sup.2 is CR.sup.2 or N; A.sup.3 is CR.sup.3 or N; A.sup.4 is CR.sup.4 or N; A.sup.5 is CR.sup.5 or N; A.sup.6 is CR.sup.6 or N; A.sup.7 is CR.sup.7 or N; A.sup.8 is CR.sup.8 or N; A.sup.9 is CR.sup.9 or N; A.sup.10 is CR.sup.10 or N; A.sup.D41 is CH, C(C.sub.1-6 alkyl) or N; A.sup.D42 is CH.sub.2, NH or NC.sub.1-6 alkyl; R.sup.2 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, C(O)OR.sup.a1, C(O)NR.sup.c1R.sup.d1 or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1; R.sup.3 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, C(O)OR.sup.a1, C(O)NR.sup.c1R.sup.d1 or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1; R.sup.4 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, C(O)OR.sup.a1, C(O)NR.sup.c1R.sup.d1 or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1; R.sup.5 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, C(O)OR.sup.a1, C(O)NR.sup.c1R.sup.d1 or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1; R.sup.6 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, S(O).sub.2R.sup.b1, S(O).sub.2NR.sup.c1R.sup.d1, NR.sup.c1R.sup.d1, C(O)OR.sup.a1, C(O)NR.sup.c1R.sup.d1, Cy.sup.7A, OCy.sup.7A, O(C.sub.1-3 alkylenyl)Cy.sup.7A, C(O)OCy.sup.7A, C(O)O(C.sub.1-3 alkylenyl)Cy.sup.7A, NHCy.sup.7A, NH(C.sub.1-3 alkylenyl)Cy.sup.7A, N(C.sub.1-6 alkyl)Cy.sup.7A, N(C(O)C.sub.1-6 alkyl)Cy.sup.7A, N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.7A, C(O)NHCy.sup.7A, C(O)NH(C.sub.1-3 alkylenyl)Cy.sup.7A, C(O)N(C.sub.1-6 alkyl)Cy.sup.7A, C(O)N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.7A, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1; R.sup.7 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, C(O)OR.sup.a1, S(O).sub.2NR.sup.c1R.sup.d1, C(O)NR.sup.c1R.sup.d1, Cy.sup.7A, OCy.sup.7A, O(C.sub.1-3 alkylenyl)Cy.sup.7A, C(O)OCy.sup.7A, C(O)O(C.sub.1-3 alkylenyl)Cy.sup.7A, NHCy.sup.7A, NH(C.sub.1-3 alkylenyl)Cy.sup.7A, N(C.sub.1-6 alkyl)Cy.sup.7A, N(C(O)C.sub.1-6 alkyl)Cy.sup.7A, N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.7A, C(O)NHCy.sup.7A, C(O)NH(C.sub.1-3 alkylenyl)Cy.sup.7A, C(O)N(C.sub.1-6 alkyl)Cy.sup.7A, C(O)N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.7A or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1 and NR.sup.c1R.sup.d1; Cy.sup.7A is C.sub.6-10 aryl, C.sub.3-15 cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkyl, wherein each of the C.sub.6-10 aryl, C.sub.3-15 cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkyl forming Cy.sup.7A is unsubstituted or substituted by 0, 1 or 2 substituents selected from Cy.sup.7B, OCy.sup.7B, NHCy.sup.7B, and C(O)NHCy.sup.7B, and 0, 1, 2, 3, 4 or 5 substituents each independently selected from unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, C(O)OR.sup.a1, C(O)NR.sup.c1R.sup.d1, and C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1; each Cy.sup.7B is C.sub.6-10 aryl, C.sub.3-15 cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkyl, wherein each of the C.sub.6-10 aryl, C.sub.3-15 cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkyl forming Cy.sup.7B is unsubstituted or substituted by 1, 2, 3, 4 or 5 substituents each independently selected from unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, C(O)OR.sup.a1, C(O)NR.sup.c1R.sup.d1, and C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1; R.sup.8 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, S(O).sub.2NR.sup.c1R.sup.d1, SR.sup.a1, NR.sup.c1R.sup.d1, , NR.sup.c1S(O).sub.2R.sup.b1, C(O)OR.sup.a1, C(O)NR.sup.c1R.sup.d1, Cy.sup.8A, OH, OCy.sup.8A, O(C.sub.1-3 alkylenyl)Cy.sup.8A, C(O)OCy.sup.8A, C(O)O(C.sub.1-3 alkylenyl)Cy.sup.8A, NHCy.sup.8A, N(Cy.sup.8A).sub.2, NH(C.sub.1-3 alkylenyl)Cy.sup.8A, N(C.sub.1-6 alkyl)Cy.sup.8A, N(C(O)C.sub.1-6 alkyl)Cy.sup.8A, SO.sub.2NHCy.sup.8A, N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.8A, C(O)NHCy.sup.8A, C.sub.1-3 alkylene-C(O)NHCy.sup.8A, C(O)NH(C.sub.1-3 alkylenyl)Cy.sup.8A, C(O)N(C.sub.1-6 alkyl)Cy.sup.8A, C(O)N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.8A, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1 and NR.sup.c1R.sup.d1; Cy.sup.8A is C.sub.6-10 aryl, C.sub.3-15 cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkyl, wherein each of the C.sub.6-10 aryl, C.sub.3-15 cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkyl forming Cy.sup.8A is unsubstituted or substituted by 0, 1 or 2 substituents selected from Cy.sup.8B, OCy.sup.8B, NHCy.sup.8B, and C(O)NHCy.sup.8B, and 0, 1, 2, 3, 4 or 5 substituents each independently selected from unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, C(O)OR.sup.a1, C(O)NR.sup.c1R.sup.d1, and C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1; each Cy.sup.8B is C.sub.6-10 aryl, C.sub.3-15 cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkyl, wherein each of the C.sub.6-10 aryl, C.sub.3-15 cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkyl forming Cy.sup.8B is unsubstituted or substituted by 1, 2, 3, 4 or 5 substituents each independently selected from unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, C(O)OR.sup.a1, C(O)NR.sup.c1R.sup.d1, and C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1; R.sup.9 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, NR.sup.c1C(O)R.sup.b1, C(O)OR.sup.a1, C(O)NR.sup.c1R.sup.d1, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1; R.sup.10 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, C(O)OR.sup.a1, C(O)NR.sup.c1R.sup.d1, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1; Cy.sup.D71 is C.sub.6-10 aryl, C.sub.3-15 cycloalkyl, 5-14 membered heteroaryl, or 4-10 membered heterocycloalkyl, wherein each of the C.sub.6-10 aryl, C.sub.3-15 cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkyl forming Cy.sup.D71 is unsubstituted or substituted by 0, 1 or 2 substituents selected from Cy.sup.D72, CH.sub.2Cy.sup.D72, OCy.sup.D72, NHCy.sup.D72, O—C.sub.1-6 alkylene-Cy.sup.D72, N(C.sub.1-6 alkyl)Cy.sup.D72, N(C(O)C.sub.1-6 alkyl)Cy.sup.D72, and C(O)NHCy.sup.D72, and 0, 1, 2, 3, 4 or 5 substituents each independently selected from unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, S(hal).sub.5, SR.sup.a1, NR.sup.c1R.sup.d1, C(O)OR.sup.a1, C(O)NR.sup.c1R.sup.d1, and C.sub.1-6 alkyl or C.sub.2-6 alkenyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, C(O)OR.sup.a1, and NR.sup.c1R.sup.d1; each Cy.sup.D72 is C.sub.6-10 aryl, C.sub.3-15 cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkyl, wherein each of the C.sub.6-10 aryl, C.sub.3-15 cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkyl forming Cy.sup.D72 is unsubstituted or substituted by 1, 2, 3, 4 or 5 substituents each independently selected from unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, C.sub.6-10 aryl, C.sub.3-15 cycloalkyl, 4-10 membered heterocycloalkyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, C(O)OR.sup.a1, C(O)NR.sup.c1R.sup.d1, and C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from C.sub.6-10 aryl, C.sub.3-15 cycloalkyl, 4-10 membered heterocycloalkyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, C(O)OR.sup.a1, and NR.sup.c1R.sup.d1 wherein said C.sub.6-10 aryl, C.sub.3-15 cycloalkyl, and 4-10 membered heterocycloalkyl are each optionally substituted with 1, 2, or 3 substituents independently selected from C.sub.1-6 alkyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, C(O)OR.sup.a1, and C(O)NR.sup.c1R.sup.d1; and R.sup.a1, R.sup.b1, R.sup.c1 and R.sup.d1 are each independently selected from H, C.sub.1-6 alkyl, C.sub.1-6 haloalkyl, HO—C.sub.1-6 alkylene, amino-C.sub.1-6 alkylene, C.sub.1-6 alkylamino-C.sub.1-6 alkylene, di(C.sub.1-6 alkyl)amino-C.sub.1-6 alkylene, C.sub.1-6 alkoxy-C.sub.1-6 alkylene, C.sub.6-10 aryl, C.sub.2-6 alkenyl and C.sub.2-6 alkynyl; or R.sup.c1 and R.sup.d1 together with the nitrogen atom to which they are both attached together form a 4-10 membered unsubstituted heterocycloalkyl ring or a heterocyclic ring that is substituted with 1, 2, or 3 substituents independently selected from C.sub.1-6 alkyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, C(O)OR.sup.a1, and C(O)NR.sup.c1R.sup.d1; provided: L.sup.1 is a group of formula N(R.sup.N) when L.sup.2 is C(O); L.sup.1 is a group of formula C(O) when L.sup.2 is N(R.sup.N); L.sup.2 is absent, or a group of formula N(R.sup.N) when L.sup.1 is C(O); L.sup.2 is absent, or a group of formula C(O) when L.sup.1 is N(R.sup.N); A.sup.D41 is CH, C(C.sub.1-6 alkyl) when A.sup.D42 is NH or NC.sub.1-6 alkyl; A.sup.D42 is CH.sub.2 when A.sup.D41 is NH or NC.sub.1-6 alkyl; no more than two of A.sup.2, A.sup.3, A.sup.4 and A.sup.5 is N; no more than two of A.sup.6, A.sup.7, A.sup.8, A.sup.9 and A.sup.10 is N; and either R.sup.1 is present and is Cy.sup.1A, OCy.sup.1A, O(C.sub.1-3 alkylenyl)Cy.sup.1A, NHCy.sup.1A, NH(C.sub.1-3 alkylenyl)Cy.sup.1A, N(C.sub.1-6 alkyl)Cy.sup.1A, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.1A; or R.sup.7 is Cy.sup.7A, OCy.sup.7A, O(C.sub.1-3 alkylenyl)Cy.sup.7A, C(O)OCy.sup.7A, C(O)O(C.sub.1-3 alkylenyl)Cy.sup.7A, NHCy.sup.7A, NH(C.sub.1-3 alkylenyl)Cy.sup.7A, N(C.sub.1-6 alkyl)Cy.sup.7A, N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.7A; C(O)NHCy.sup.7A, C(O)NH(C.sub.1-3 alkylenyl)Cy.sup.7A, C(O)N(C.sub.1-6 alkyl)Cy.sup.7A, or C(O)N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.7A, or R.sup.8 is Cy.sup.8A, OCy.sup.8A, O(C.sub.1-3 alkylenyl)Cy.sup.8A, C(O)OCy.sup.8A, C(O)O(C.sub.1-3 alkylenyl)Cy.sup.8A, NHCy.sup.8A, NH(C.sub.1-3 alkylenyl)Cy.sup.8A, N(C.sub.1-6 alkyl)Cy.sup.8A, N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.8A, C(O)NHCy.sup.8A, C(O)NH(C.sub.1-3 alkylenyl)Cy.sup.8A, C(O)N(C.sub.1-6 alkyl)Cy.sup.8A, or C(O)N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.8A.

2. The compound of claim 1, wherein: R.sup.6 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, C(O)OR.sup.a1, C(O)NR.sup.c1R.sup.d1, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1; R.sup.7 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, C(O)OR.sup.a1, C(O)NR.sup.c1R.sup.d1, Cy.sup.7A, OCy.sup.7A, O(C.sub.1-3 alkylenyl)Cy.sup.7A, C(O)OCy.sup.7A, C(O)O(C.sub.1-3 alkylenyl)Cy.sup.7A, NHCy.sup.7A, NH(C.sub.1-3 alkylenyl)Cy.sup.7A, N(C.sub.1-6 alkyl)Cy.sup.7A, N(C(O)C.sub.1-6 alkyl)Cy.sup.7A, N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.7A, C(O)NHCy.sup.7A, C(O)NH(C.sub.1-3 alkylenyl)Cy.sup.7A, C(O)N(C.sub.1-6 alkyl)Cy.sup.7A, C(O)N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.7A or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1; R.sup.8 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, C(O)OR.sup.a1, C(O)NR.sup.c1R.sup.d1, Cy.sup.8A, OH, OCy.sup.8A, O(C.sub.1-3 alkylenyl)Cy.sup.8A, C(O)OCy.sup.8A, C(O)O(C.sub.1-3 alkylenyl)Cy.sup.8A, NHCy.sup.8A, N(Cy.sup.8A).sub.2, NH(C.sub.1-3 alkylenyl)Cy.sup.8A, N(C.sub.1-6 alkyl)Cy.sup.8A, N(C(O)C.sub.1-6 alkyl)Cy.sup.8A, SO.sub.2NHCy.sup.8A, N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.8A, C(O)NHCy.sup.8A, C.sub.1-3 alkylene-C(O)NHCy.sup.8A, C(O)NH(C.sub.1-3 alkylenyl)Cy.sup.8A, C(O)N(C.sub.1-6 alkyl)Cy.sup.8A, C(O)N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.8A, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1; R.sup.9 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, C(O)OR.sup.a1, C(O)NR.sup.c1R.sup.d1, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1; Cy.sup.D71 is C.sub.6-10 aryl, C.sub.3-15 cycloalkyl, 5-14 membered heteroaryl, or 4-10 membered heterocycloalkyl, wherein each of the C.sub.6-10 aryl, C.sub.3-15 cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkyl forming Cy.sup.D71 is unsubstituted or substituted by 0, 1 or 2 substituents selected from Cy.sup.D72, CH.sub.2Cy.sup.D72, OCy.sup.D72, NHCy.sup.D72, O—C.sub.1-6 alkylene-Cy.sup.D72, N(C.sub.1-6 alkyl)Cy.sup.D72, N(C(O)C.sub.1-6 alkyl)Cy.sup.D72, and C(O)NHCy.sup.D72, and 0, 1, 2, 3, 4 or 5 substituents each independently selected from unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, C(O)OR.sup.a1, C(O)NR.sup.c1R.sup.d1, and C.sub.1-6 alkyl or C.sub.2-6 alkenyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, C(O)OR.sup.a1, and NR.sup.c1R.sup.d1; each Cy.sup.D72 is C.sub.6-10 aryl, C.sub.3-15 cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkyl, wherein each of the C.sub.6-10 aryl, C.sub.3-15 cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkyl forming Cy.sup.D72 is unsubstituted or substituted by 1, 2, 3, 4 or 5 substituents each independently selected from unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, C.sub.3-15 cycloalkyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, C(O)OR.sup.a1, C(O)NR.sup.c1R.sup.d1, and C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, C(O)OR.sup.a1, and NR.sup.c1R.sup.d1; and R.sup.a1, R.sup.b1, R.sup.c1 and R.sup.d1 are each independently selected from H, C.sub.1-6 alkyl, HO—C.sub.1-6 alkylene, C.sub.1-6 alkoxy-C.sub.1-6 alkylene, C.sub.6-10 aryl, C.sub.2-6 alkenyl and C.sub.2-6 alkynyl; or R.sup.c1 and R.sup.d1 together with the nitrogen atom to which they are both attached together form a 4-10 membered unsubstituted heterocycloalkyl ring.

3-4. (canceled)

5. The compound or pharmaceutically acceptable salt thereof of claim 1, wherein D is a group of formula (D1).

6. The compound or pharmaceutically acceptable salt thereof of claim 1, wherein D is a group of formula (D2).

7. The compound or pharmaceutically acceptable salt thereof of claim 1, wherein D is a group of formula (D3).

8-30. (canceled)

31. The compound or pharmaceutically acceptable salt thereof of claim 1, wherein D is a group of formula (D4).

32-40. (canceled)

41. The compound or pharmaceutically acceptable salt thereof of claim 1, wherein D is a group of formula (D5).

42-44. (canceled)

45. The compound or pharmaceutically acceptable salt thereof of claim 1, wherein D is a group of formula (D6).

46. (canceled)

47. The compound or pharmaceutically acceptable salt thereof of claim 45, wherein m is 2.

48-50. (canceled)

51. The compound or pharmaceutically acceptable salt thereof of claim 47, wherein R.sup.1 is NHCy.sup.1A.

52-53. (canceled)

54. The compound or pharmaceutically acceptable salt thereof of claim 51, wherein R.sup.1 is a group of one of the following formulae: ##STR01804## wherein: R.sup.11 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.1B, OH, OCy.sup.1B, O(C.sub.1-3 alkylenyl)Cy.sup.1B, NHCy.sup.1B, NH(C.sub.1-3 alkylenyl)Cy.sup.1B, N(C.sub.1-6 alkyl)Cy.sup.1B, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.1B, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1; R.sup.12 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.1B, OH, OCy.sup.1B, O(C.sub.1-3 alkylenyl)Cy.sup.1B, NHCy.sup.1B, NH(C.sub.1-3 alkylenyl)Cy.sup.1B, N(C.sub.1-6 alkyl)Cy.sup.1B, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.1B, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1; R.sup.13 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.1B, OH, OCy.sup.1B, O(C.sub.1-3 alkylenyl)Cy.sup.1B, NHCy.sup.1B, NH(C.sub.1-3 alkylenyl)Cy.sup.1B, N(C.sub.1-6 alkyl)Cy.sup.1B, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.1B, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1; R.sup.14 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.1B, OH, OCy.sup.1B, O(C.sub.1-3 alkylenyl)Cy.sup.1B, NHCy.sup.1B, NH(C.sub.1-3 alkylenyl)Cy.sup.1B, N(C.sub.1-6 alkyl)Cy.sup.1B, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.1B, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1; R.sup.15 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.1B, OH, OCy.sup.1B, O(C.sub.1-3 alkylenyl)Cy.sup.1B, NHCy.sup.1B, NH(C.sub.1-3 alkylenyl)Cy.sup.1B, N(C.sub.1-6 alkyl)Cy.sup.1B, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.1B, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1; R.sup.16 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.1B, OH, OCy.sup.1B, O(C.sub.1-3 alkylenyl)Cy.sup.1B, NHCy.sup.1B, NH(C.sub.1-3 alkylenyl)Cy.sup.1B, N(C.sub.1-6 alkyl)Cy.sup.1B, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.1B, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1; R.sup.17 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.1B, OH, OCy.sup.1B, O(C.sub.1-3 alkylenyl)Cy.sup.1B, NHCy.sup.1B, NH(C.sub.1-3 alkylenyl)Cy.sup.1B, N(C.sub.1-6 alkyl)Cy.sup.1B, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.1B, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1; and R.sup.18 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.1B, OH, OCy.sup.1B, O(C.sub.1-3 alkylenyl)Cy.sup.1B, NHCy.sup.1B, NH(C.sub.1-3 alkylenyl)Cy.sup.1B, N(C.sub.1-6 alkyl)Cy.sup.1B, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.1B, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1.

55. The compound or pharmaceutically acceptable salt thereof of claim 54, wherein R.sup.1 is a group of one of the following formulae: ##STR01805##

56-118. (canceled)

119. The compound or pharmaceutically acceptable salt thereof of claim 1, wherein the compound is a compound of one of the following formulae (I-1) to (I-60): ##STR01806## ##STR01807## ##STR01808## ##STR01809## ##STR01810## ##STR01811## ##STR01812## ##STR01813## ##STR01814## ##STR01815## wherein: R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.8, R.sup.9, R.sup.10, R.sup.N, A.sup.1, A.sup.2, A.sup.3, A.sup.4, A.sup.5, A.sup.6, A.sup.7, A.sup.8, A.sup.9, A.sup.10, Cy.sup.1A, Cy.sup.1B, Cy.sup.7A, Cy.sup.7B, Cy.sup.8A, Cy.sup.8B, L.sup.1 and L.sup.2, are as defined in claim 1; L.sup.7 is absent, O, NH or N(C.sub.1-6 alkyl); L.sup.8 is absent, O, NH or N(C.sub.1-6 alkyl); R.sup.11 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.1B, OH, OCy.sup.1B, O(C.sub.1-3 alkylenyl)Cy.sup.1B, NHCy.sup.1B, NH(C.sub.1-3 alkylenyl)Cy.sup.1B, N(C.sub.1-6 alkyl)Cy.sup.1B, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.1B, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1; R.sup.12 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.1B, OH, OCy.sup.1B, O(C.sub.1-3 alkylenyl)Cy.sup.1B, NHCy.sup.1B, NH(C.sub.1-3 alkylenyl)Cy.sup.1B, N(C.sub.1-6 alkyl)Cy.sup.1B, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.1B, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1; R.sup.13 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.1B, OH, OCy.sup.1B, O(C.sub.1-3 alkylenyl)Cy.sup.1B, NHCy.sup.1B, NH(C.sub.1-3 alkylenyl)Cy.sup.1B, N(C.sub.1-6 alkyl)Cy.sup.1B, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.1B, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1; R.sup.14 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.1B, OH, OCy.sup.1B, O(C.sub.1-3 alkylenyl)Cy.sup.1B, NHCy.sup.1B, NH(C.sub.1-3 alkylenyl)Cy.sup.1B, N(C.sub.1-6 alkyl)Cy.sup.1B, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.1B, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1; R.sup.15 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.1B, OH, OCy.sup.1B, O(C.sub.1-3 alkylenyl)Cy.sup.1B, NHCy.sup.1B, NH(C.sub.1-3 alkylenyl)Cy.sup.1B, N(C.sub.1-6 alkyl)Cy.sup.1B, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.1B, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1; R.sup.16 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.1B, OH, OCy.sup.1B, O(C.sub.1-3 alkylenyl)Cy.sup.1B, NHCy.sup.1B, NH(C.sub.1-3 alkylenyl)Cy.sup.1B, N(C.sub.1-6 alkyl)Cy.sup.1B, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.1B, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1; R.sup.17 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.1B, OH, OCy.sup.1B, O(C.sub.1-3 alkylenyl)Cy.sup.1B, NHCy.sup.1B, NH(C.sub.1-3 alkylenyl)Cy.sup.1B, N(C.sub.1-6 alkyl)Cy.sup.1B, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.1B, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1; R.sup.18 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.1B, OH, OCy.sup.1B, O(C.sub.1-3 alkylenyl)Cy.sup.1B, NHCy.sup.1B, NH(C.sub.1-3 alkylenyl)Cy.sup.1B, N(C.sub.1-6 alkyl)Cy.sup.1B, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.1B, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1; R.sup.71 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.7B, OH, OCy.sup.7B, O(C.sub.1-3 alkylenyl)Cy.sup.7B, NHCy.sup.7B, NH(C.sub.1-3 alkylenyl)Cy.sup.7B, N(C.sub.1-6 alkyl)Cy.sup.7B, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.7B, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1; R.sup.72 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.7B, OH, OCy.sup.7B, O(C.sub.1-3 alkylenyl)Cy.sup.7B, NHCy.sup.7B, NH(C.sub.1-3 alkylenyl)Cy.sup.7B, N(C.sub.1-6 alkyl)Cy.sup.7B, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.7B, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1; R.sup.73 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.7B, OH, OCy.sup.7B, O(C.sub.1-3 alkylenyl)Cy.sup.7B, NHCy.sup.7B, NH(C.sub.1-3 alkylenyl)Cy.sup.7B, N(C.sub.1-6 alkyl)Cy.sup.7B, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.7B, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1; R.sup.74 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.7B, OH, OCy.sup.7B, O(C.sub.1-3 alkylenyl)Cy.sup.7B, NHCy.sup.7B, NH(C.sub.1-3 alkylenyl)Cy.sup.7B, N(C.sub.1-6 alkyl)Cy.sup.7B, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.7B, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1; R.sup.75 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.7B, OH, OCy.sup.7B, O(C.sub.1-3 alkylenyl)Cy.sup.7B, NHCy.sup.7B, NH(C.sub.1-3 alkylenyl)Cy.sup.7B, N(C.sub.1-6 alkyl)Cy.sup.7B, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.7B, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1; R.sup.76 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.7B, OH, OCy.sup.7B, O(C.sub.1-3 alkylenyl)Cy.sup.7B, NHCy.sup.7B, NH(C.sub.1-3 alkylenyl)Cy.sup.7B, N(C.sub.1-6 alkyl)Cy.sup.7B, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.7B, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1; R.sup.77 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.7B, OH, OCy.sup.7B, O(C.sub.1-3 alkylenyl)Cy.sup.7B, NHCy.sup.7B, NH(C.sub.1-3 alkylenyl)Cy.sup.7B, N(C.sub.1-6 alkyl)Cy.sup.7B, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.7B, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1; and R.sup.78 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.7B, OH, OCy.sup.7B, O(C.sub.1-3 alkylenyl)Cy.sup.7B, NHCy.sup.7B, NH(C.sub.1-3 alkylenyl)Cy.sup.7B, N(C.sub.1-6 alkyl)Cy.sup.7B, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.7B, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1; R.sup.81 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.8B, OH, OCy.sup.8B, O(C.sub.1-3 alkylenyl)Cy.sup.8B, NHCy.sup.8B, NH(C.sub.1-3 alkylenyl)Cy.sup.8B, N(C.sub.1-6 alkyl)Cy.sup.8B, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.8B, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1; R.sup.82 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.8B, OH, OCy.sup.8B, O(C.sub.1-3 alkylenyl)Cy.sup.8B, NHCy.sup.8B, NH(C.sub.1-3 alkylenyl)Cy.sup.8B, N(C.sub.1-6 alkyl)Cy.sup.8B, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.8B, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1; R.sup.83 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.8B, OH, OCy.sup.8B, O(C.sub.1-3 alkylenyl)Cy.sup.8B, NHCy.sup.8B, NH(C.sub.1-3 alkylenyl)Cy.sup.8B, N(C.sub.1-6 alkyl)Cy.sup.8B, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.8B, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1; R.sup.84 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.8B, OH, OCy.sup.8B, O(C.sub.1-3 alkylenyl)Cy.sup.8B, NHCy.sup.8B, NH(C.sub.1-3 alkylenyl)Cy.sup.8B, N(C.sub.1-6 alkyl)Cy.sup.8B, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.8B, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1; R.sup.85 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.8B, OH, OCy.sup.8B, O(C.sub.1-3 alkylenyl)Cy.sup.8B, NHCy.sup.8B, NH(C.sub.1-3 alkylenyl)Cy.sup.8B, N(C.sub.1-6 alkyl)Cy.sup.8B, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.8B, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1; R.sup.86 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.8B, OH, OCy.sup.8B, O(C.sub.1-3 alkylenyl)Cy.sup.8B, NHCy.sup.8B, NH(C.sub.1-3 alkylenyl)Cy.sup.8B, N(C.sub.1-6 alkyl)Cy.sup.8B, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.8B, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1; R.sup.87 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.8B, OH, OCy.sup.8B, O(C.sub.1-3 alkylenyl)Cy.sup.8B, NHCy.sup.8B, NH(C.sub.1-3 alkylenyl)Cy.sup.8B, N(C.sub.1-6 alkyl)Cy.sup.8B, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.8B, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1; and R.sup.88 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.8B, OH, OCy.sup.8B, O(C.sub.1-3 alkylenyl)Cy.sup.8B, NHCy.sup.8B, NH(C.sub.1-3 alkylenyl)Cy.sup.8B, N(C.sub.1-6 alkyl)Cy.sup.8B, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.8B, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1.

120-124. (canceled)

125. The compound or pharmaceutically acceptable salt thereof of claim 1, wherein the compound is a compound of one of the following formulae: ##STR01816## ##STR01817## ##STR01818## ##STR01819## ##STR01820## ##STR01821## ##STR01822## ##STR01823## ##STR01824## ##STR01825## ##STR01826## ##STR01827## ##STR01828## ##STR01829## ##STR01830## ##STR01831## ##STR01832## ##STR01833## ##STR01834## ##STR01835## ##STR01836## ##STR01837## ##STR01838## ##STR01839## ##STR01840## ##STR01841## ##STR01842## ##STR01843## ##STR01844## ##STR01845## ##STR01846## ##STR01847## ##STR01848## ##STR01849## ##STR01850## ##STR01851## ##STR01852## ##STR01853## ##STR01854## ##STR01855## ##STR01856## ##STR01857##

126. A compound or claim 1, or a pharmaceutically acceptable salt thereof, wherein the compound of formula (I) is selected from any one of the following compounds: ##STR01858## ##STR01859## ##STR01860## ##STR01861## ##STR01862## ##STR01863## ##STR01864## ##STR01865## ##STR01866## ##STR01867## ##STR01868## ##STR01869## ##STR01870## ##STR01871##

127. A pharmaceutical composition comprising a compound of claim 1, or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier.

128-129. (canceled)

130. A method of treating cancer comprising administering to a patient in need of such treatment a therapeutically effective amount of a compound of claim 1, or a pharmaceutically acceptable salt thereof.

131. The method of claim 130, wherein the cancer is a solid tumor or a hematological cancer.

132. The method of claim 130, wherein the cancer is prostate cancer, colon cancer, esophageal cancer, endometrial cancer, ovarian cancer, uterine cancer, renal cancer, hepatic cancer, pancreatic cancer, gastric cancer, breast cancer, lung cancer, cancer of the head or neck, thyroid cancer, glioblastoma, sarcoma, bladder cancer, lymphoma, leukemia, acute lymphoblastic leukemia, acute myelogenous leukemia, chronic lymphocytic leukemia, chronic myelogenous leukemia, diffuse large-B cell lymphoma, mantle cell lymphoma, non-Hodgkin lymphoma, Hodgkin lymphoma or multiple myeloma.

133. The method of claim 130, wherein the cancer is hepatocellular carcinoma, medulloblastoma, cutaneous squamous cell carcinoma, lung cancer, pancreatic cancer, esophagus cancer, liver cancer, colon cancer, melanoma, or uveal melanoma.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0011] FIG. 1 scheme showing the structures of examples of compounds within the scope of the invention.

[0012] FIG. 2 is a scheme showing the structures of some reference compounds.

[0013] FIG. 3 is a picture showing the result of streptavidin and histidine blots showing the results of assays of the inhibition of TEAD2 in vitro autopalmitoylation by the compounds CP-1, flufenamic acid, CP-41, CP-42, CP-51, CP-52, CP-53, CP-54, CP-55, CP-56, CP-57, and CP-58.

[0014] FIG. 4 is a picture showing the result of streptavidin and histidine blots showing the results of assays of the inhibition of TEAD2 in vitro autopalmitoylation by the compound CP-55 at various concentrations.

[0015] FIG. 5 is a collection of plots showing inhibition of cell proliferation in the 92.1 uveal melanoma cell line, cellosaurus OCM1 cell line, human hepatoma huh7 cell line, SNU398 human liver hepatocellular carcinoma cell line, and the MDA-MB-453 human mammary gland metastatic carcinoma cell line by the compound CP-55 at various concentrations.

[0016] FIG. 6 is collection of plots showing inhibition of gene expression for the CYR61, CTGF and ANKRD1 genes in the huh7 human hepatoma cell line by the compound CP-55 at various time points and concentrations.

[0017] FIG. 7 is a picture showing the result of streptavidin and histidine blots showing the results of assays of the inhibition of TEAD2 in vitro autopalmitoylation by the compound CP-58 at various concentrations.

[0018] FIG. 8 is a plot showing inhibition of cell proliferation in the 92.1 uveal melanoma cell line by the compounds CP-1, CP-52, CP-55 and CP-58 at various concentrations.

[0019] FIG. 9 is a plot showing inhibition of cell proliferation in the huh7 human hepatoma cell line by the compound CP-57 at various concentrations.

[0020] FIG. 10 is a plot showing inhibition of cell proliferation in the huh7 human hepatoma cell line by the compound CP-58 at various concentrations.

[0021] FIG. 11 is a pair of plots showing inhibition of gene expression for the genes CYR61 and CTGF and ANKRD1 genes in the huh7 human hepatoma cell line by the compound CP-58 after 24 h compared to control.

[0022] FIG. 12 is a picture showing the result of streptavidin and histidine blots showing the results of assays of the inhibition of TEAD2 in vitro autopalmitoylation by the compounds CP-1, CP-55, CP-58, CP-59, CP-60, CP-61 and CP-62.

[0023] FIG. 13 is a plot inhibition of cell proliferation in the huh7 human hepatoma cell line by the compounds CP-58, CP-59, CP-60, CP-61 and CP-62 at various concentrations.

DETAILED DESCRIPTION

[0024] For the terms “e.g.” and “such as,” and grammatical equivalents thereof, the phrase “and without limitation” is understood to follow unless explicitly stated otherwise.

[0025] The singular forms “a,” “an,” and “the” include plural referents unless the context clearly dictates otherwise.

[0026] The term “about” means “approximately” (e.g., plus or minus approximately 10% of the indicated value).

[0027] The expressions, “ambient temperature” and “room temperature” (abbreviated “r.t.”) refer generally to a temperature, e.g., a reaction temperature, that is about the temperature of the room in which the reaction is carried out, e.g., a temperature from about 20° C. to about 30° C., typically about 25° C.

[0028] Through proteomic and biochemical studies, it has been identified that the TEAD transcription factors are palmitoylated at evolutionarily conserved cysteine residues. It has been found that TEADs undergo PAT-independent autopalmitoylation, under physiological concentrations of palmitoyl-CoA. The crystal structures of the lipid-bound TEADs, and revealed a new ligand-binding site in TEADs. Furthermore, autopalmitoylation plays critical roles in regulating TEAD-YAP association and their physiological functions in vitro and in vivo. Therefore, palmitoylation of TEADs plays important roles in regulating Hippo pathway transcriptional complexes.

[0029] The discovery of a new ligand-binding site in TEADs has allowed the discovery of small molecule inhibitors of TEAD autopalmitoylation. While not being bound by any theory, it is understood that the ligands bind to the palmitate-binding pocket, and inhibit TEAD-YAP interaction, cancer cell proliferation and migration. Therefore, direct inhibition of TEAD autopalmitoylation activities is useful to inhibit these oncogenic transcription factors.

I. Compounds

[0030] The present disclosure provides, inter alia, a compound of Formula (I):

##STR00002##

[0031] or a pharmaceutically acceptable salt thereof, wherein: [0032] L.sup.1 is absent, or a group of formula N(R.sup.N) or C(O); [0033] D is a group of formula (D1), (D2), (D3), (D4), (D5), (D6) or (D7):

##STR00003## [0034] m is 1, 2 or 3; [0035] A.sup.1 is C(O)R.sup.1, S(O).sub.2R.sup.1, NHC(O)R.sup.1, (C.sub.1-3 alkylene)-C(O)R.sup.1, NH(C.sub.1-3 alkylene)-C(O)R.sup.1, CN, NO.sub.2, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, (C.sub.1-3 alkylene)-5-10 membered heteroaryl, or (C.sub.1-3 alkylene)-4-10 membered heterocycloalkyl, wherein the (C.sub.1-3 alkylene) group of the (C.sub.1-3 alkylene)-C(O)R.sup.1 group forming A.sup.1 is unsubstituted or substituted by 1, 2, 3, 4 or 5 substituents each independently selected from halogen, OR.sup.a1, NR.sup.c1R.sup.d1, NR.sup.a1(CO)(C.sub.1-6 alkyl), and NR.sup.a1(CO)O(C.sub.1-6 alkyl); and wherein the 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, (C.sub.1-3 alkylene)-5-10 membered heteroaryl, or (C.sub.1-3 alkylene)-4-10 membered heterocycloalkyl forming A.sup.1 is unsubstituted or substituted by 1, 2, 3, 4 or 5 substituents each independently selected from halogen, OR.sup.a1, SR.sup.a1, C(O)OR.sup.a1, NR.sup.c1R.sup.d1, and C(O)NR.sup.c1R.sup.d1; [0036] L.sup.2 is absent, or a group of formula N(R.sup.N), O, or C(O); [0037] L.sup.3 is absent or a group of formula CH.sub.2, C≡C, N(R.sup.N) or C(O); [0038] each R.sup.N is independently H, C.sub.1-6 alkyl, C(O)C.sub.1-6 alkyl, or C(O)OC.sub.1-6 alkyl; [0039] R.sup.1 is H, C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, Cy.sup.1A, OH, OC.sub.1-6 alkyl, OCy.sup.1AO(C.sub.1-3 alkylenyl)Cy.sup.1A, NH.sub.2, NHC.sub.1-6 alkyl, N(C.sub.1-6 alkyl).sub.2, NHCy.sup.1A, NH(C.sub.1-3 alkylenyl)Cy.sup.1A, N(C.sub.1-6 alkyl)Cy.sup.1A, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.1A, wherein each of the C.sub.1-6 alkyl forming R.sup.1 is unsubstituted or substituted by 1, 2, 3, 4 or 5 substituents each independently selected from halogen, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1; [0040] Cy.sup.1A is C.sub.6-10 aryl, C.sub.3-15 cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkyl, wherein each of the C.sub.6-10 aryl, C.sub.3-15 cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkyl forming Cy.sup.1A is unsubstituted or substituted by 0, 1 or 2 Cy.sup.1B and 0, 1, 2, 3, 4 or 5 substituents each independently selected from unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, and C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1; [0041] each Cy.sup.1B is C.sub.6-10 aryl, C.sub.3-15 cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkyl, wherein each of the C.sub.6-10 aryl, C.sub.3-15 cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkyl forming Cy.sup.1B is unsubstituted or substituted by 1, 2, 3, 4 or 5 substituents each independently selected from unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1 SR.sup.a1, and NR.sup.c1R.sup.d1; and C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1; [0042] A.sup.2 is CR.sup.2 or N; [0043] A.sup.3 is CR.sup.3 or N; [0044] A.sup.4 is CR.sup.4 or N; [0045] A.sup.5 is CR.sup.5 or N; [0046] A.sup.6 is CR.sup.6 or N; [0047] A.sup.7 is CR.sup.7 or N; [0048] A.sup.8 is CR.sup.8 or N; [0049] A.sup.9 is CR.sup.9 or N; [0050] A.sup.10 is CR.sup.10 or N; [0051] A.sup.D41 is CH, C(C.sub.1-6 alkyl) or N; [0052] A.sup.D42 is CH.sub.2, NH or NC.sub.1-6 alkyl; [0053] R.sup.2 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, C(O)OR.sup.a1, C(O)NR.sup.c1R.sup.d1 or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1; [0054] R.sup.3 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, C(O)OR.sup.a1, C(O)NR.sup.c1R.sup.d1 or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1; [0055] R.sup.4 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, C(O)OR.sup.a1, C(O)NR.sup.c1R.sup.d1 or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1; [0056] R.sup.5 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, C(O)OR.sup.a1, C(O)NR.sup.c1R.sup.d1 or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1; [0057] R.sup.6 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, S(O).sub.2R.sup.b1, S(O).sub.2NR.sup.c1R.sup.d1, NR.sup.c1R.sup.d1, C(O)OR.sup.a1, C(O)NR.sup.c1R.sup.d1, Cy.sup.7A, OCy.sup.7A, O(C.sub.1-3 alkylenyl)Cy.sup.7A, C(O)OCy.sup.7A, C(O)O(C.sub.1-3 alkylenyl)Cy.sup.7A, NHCy.sup.7ANH(C.sub.1-3 alkylenyl)Cy.sup.7A, N(C.sub.1-6 alkyl)Cy.sup.7A, N(C(O)C.sub.1-6 alkyl)Cy.sup.7A, N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.7A, C(O)NHCy.sup.7A, C(O)NH(C.sub.1-3 alkylenyl)Cy.sup.7A, C(O)N(C.sub.1-6 alkyl)Cy.sup.7A, C(O)N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.7A, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1; [0058] R.sup.7 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, C(O)OR.sup.a1, S(O).sub.2NR.sup.c1R.sup.d1, C(O)NR.sup.c1R.sup.d1, Cy.sup.7A, OCy.sup.7A, O(C.sub.1-3 alkylenyl)Cy.sup.7A, C(O)OCy.sup.7A, C(O)O(C.sub.1-3 alkylenyl)Cy.sup.7A, NHCy.sup.7A, NH(C.sub.1-3 alkylenyl)Cy.sup.7A, N(C.sub.1-6 alkyl)Cy.sup.7A, N(C(O)C.sub.1-6 alkyl)Cy.sup.7A, N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.7A, C(O)NHCy.sup.7A, C(O)NH(C.sub.1-3 alkylenyl)Cy.sup.7A, C(O)N(C.sub.1-6 alkyl)Cy.sup.7A, C(O)N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.7A or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1; [0059] Cy.sup.7A is C.sub.6-10 aryl, C.sub.3-15 cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkyl, wherein each of the C.sub.6-10 aryl, C.sub.3-15 cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkyl forming Cy.sup.7A is unsubstituted or substituted by 0, 1 or 2 substituents selected from Cy.sup.7B, OCy.sup.7B, NHCy.sup.7B, and C(O)NHCy.sup.7B, and 0, 1, 2, 3, 4 or 5 substituents each independently selected from unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, C(O)OR.sup.a1, C(O)NR.sup.c1R.sup.d1, and C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1; [0060] each Cy.sup.7B is C.sub.6-10 aryl, C.sub.3-15 cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkyl, wherein each of the C.sub.6-10 aryl, C.sub.3-15 cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkyl forming Cy.sup.7B is unsubstituted or substituted by 1, 2, 3, 4 or 5 substituents each independently selected from unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, C(O)OR.sup.a1, C(O)NR.sup.c1R.sup.d1, and C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1; [0061] R.sup.8 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, S(O).sub.2NR.sup.c1R.sup.d1, SR.sup.a1, NR.sup.c1R.sup.d1, NR.sup.c1S(O).sub.2R.sup.b1, C(O)OR.sup.a1, C(O)NR.sup.c1R.sup.d1, Cy.sup.8A, OH, OCy.sup.8A, O(C.sub.1-3 alkylenyl)Cy.sup.8A, C(O)OCy.sup.8A, C(O)O(C.sub.1-3 alkylenyl)Cy.sup.8A, NHCy.sup.8A, N(Cy.sup.8A).sub.2, NH(C.sub.1-3 alkylenyl)Cy.sup.8A, N(C.sub.1-6 alkyl)Cy.sup.8A, N(C(O)C.sub.1-6 alkyl)Cy.sup.8A, SO.sub.2NHCy.sup.8A, N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.8A, C(O)NHCy.sup.8A, C.sub.1-3 alkylene-C(O)NHCy.sup.8A, C(O)NH(C.sub.1-3 alkylenyl)Cy.sup.8A, C(O)N(C.sub.1-6 alkyl)Cy.sup.8A, C(O)N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.8A, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1; [0062] Cy.sup.8A is C.sub.6-10 aryl, C.sub.3-15 cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkyl, wherein each of the C.sub.6-10 aryl, C.sub.3-15 cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkyl forming Cy.sup.8A is unsubstituted or substituted by 0, 1 or 2 substituents selected from Cy.sup.8B, OCy.sup.8B, NHCy.sup.8B, and C(O)NHCy.sup.8B, and 0, 1, 2, 3, 4 or 5 substituents each independently selected from unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, C(O)OR.sup.a1, C(O)NR.sup.c1R.sup.d1, and C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1; [0063] each Cy.sup.8B is C.sub.6-10 aryl, C.sub.3-15 cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkyl, wherein each of the C.sub.6-10 aryl, C.sub.3-15 cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkyl forming Cy.sup.8B is unsubstituted or substituted by 1, 2, 3, 4 or 5 substituents each independently selected from unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1 SR.sup.a1, NR.sup.c1R.sup.d1, C(O)OR.sup.a1, C(O)NR.sup.c1R.sup.d1, and C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1; [0064] R.sup.9 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, NR.sup.c1C(O)R.sup.b1, C(O)OR.sup.a1, C(O)NR.sup.c1R.sup.d1, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1; [0065] R.sup.10 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, C(O)OR.sup.a1, C(O)NR.sup.c1R.sup.d1, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1; [0066] Cy.sup.D71 is C.sub.6-10 aryl, C.sub.3-15 cycloalkyl, 5-14 membered heteroaryl, or 4-10 membered heterocycloalkyl, wherein each of the C.sub.6-10 aryl, C.sub.3-15 cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkyl forming Cy.sup.D71 is unsubstituted or substituted by 0, 1 or 2 substituents selected from Cy.sup.D72, CH.sub.2Cy.sup.D72, OCy.sup.D72, NHCy.sup.D72, O—C.sub.1-6 alkylene-Cy.sup.D72, N(C.sub.1-6 alkyl)Cy.sup.D72, N(C(O)C.sub.1-6 alkyl)Cy.sup.D72, and C(O)NHCy.sup.D72, and 0, 1, 2, 3, 4 or 5 substituents each independently selected from unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, S(hal).sub.5, SR.sup.a1, NR.sup.c1R.sup.d1, C(O)OR.sup.a1, C(O)NR.sup.c1R.sup.d1, and C.sub.1-6 alkyl or C.sub.2-6 alkenyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, C(O)OR.sup.a1, and NR.sup.c1R.sup.d1; [0067] each Cy.sup.D72 is C.sub.6-10 aryl, C.sub.3-15 cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkyl, wherein each of the C.sub.6-10 aryl, C.sub.3-15 cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkyl forming Cy.sup.D72 is unsubstituted or substituted by 1, 2, 3, 4 or 5 substituents each independently selected from unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, C.sub.6-10 aryl, C.sub.3-15 cycloalkyl, 4-10 membered heterocycloalkyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, C(O)OR.sup.a1, C(O)NR.sup.c1R.sup.d1, and C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from C.sub.6-10 aryl, C.sub.3-15 cycloalkyl, 4-10 membered heterocycloalkyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, C(O)OR.sup.a1, and NR.sup.c1R.sup.d1, wherein said C.sub.6-10 aryl, C.sub.3-15 cycloalkyl, and 4-10 membered heterocycloalkyl are each optionally substituted with 1, 2, or 3 substituents independently selected from C.sub.1-6 alkyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, C(O)OR.sup.a1, and C(O)NR.sup.c1R.sup.d1; and [0068] R.sup.a1, R.sup.b1, R.sup.c1 and R.sup.d1 are each independently selected from H, C.sub.1-6 alkyl, C.sub.1-6 haloalkyl, HO—C.sub.1-6 alkylene, amino-C.sub.1-6 alkylene, C.sub.1-6 alkylamino-C.sub.1-6 alkylene, di(C.sub.1-6 alkyl)amino-C.sub.1-6 alkylene, C.sub.1-6 alkoxy-C.sub.1-6 alkylene, C.sub.6-10 aryl, C.sub.2-6 alkenyl and C.sub.2-6 alkynyl; or [0069] R.sup.c1 and R.sup.d1 together with the nitrogen atom to which they are both attached together form a 4-10 membered unsubstituted heterocycloalkyl ring or a heterocyclic ring that is substituted with 1, 2, or 3 substituents independently selected from C.sub.1-6 alkyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, C(O)OR.sup.a1, and C(O)NR.sup.c1R.sup.d1; [0070] provided: [0071] L.sup.1 is a group of formula N(R.sup.N) when L.sup.2 is C(O); [0072] L.sup.1 is a group of formula C(O) when L.sup.2 is N(R.sup.N); [0073] L.sup.2 is absent, or a group of formula N(R.sup.N) when L.sup.1 is C(O); [0074] L.sup.2 is absent, or a group of formula C(O) when L.sup.1 is N(R.sup.N); [0075] A.sup.D41 is CH, C(C.sub.1-6 alkyl) when A.sup.D42 is NH or NC.sub.1-6 alkyl; [0076] A.sup.D42 is CH.sub.2 when A.sup.D41 is NH or NC.sub.1-6 alkyl; [0077] no more than two of A.sup.2, A.sup.3, A.sup.4 and A.sup.5 is N; [0078] no more than two of A.sup.6, A.sup.7, A.sup.8, A.sup.9 and A.sup.10 is N; and [0079] either R.sup.1 is present and is Cy.sup.1A, OCy.sup.1A, O(C.sub.1-3 alkylenyl)Cy.sup.1A, NHCy.sup.1A NH(C.sub.1-3 alkylenyl)Cy.sup.1A, N(C.sub.1-6 alkyl)Cy.sup.1A, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.1A; or [0080] R.sup.7 is Cy.sup.7A, OCy.sup.7A, O(C.sub.1-3 alkylenyl)Cy.sup.7A, C(O)OCy.sup.7A, C(O)O(C.sub.1-3 alkylenyl)Cy.sup.7A, NHCy.sup.7A, NH(C.sub.1-3 alkylenyl)Cy.sup.7A, N(C.sub.1-6 alkyl)Cy.sup.7A, N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.7A; C(O)NHCy.sup.7A, C(O)NH(C.sub.1-3 alkylenyl)Cy.sup.7A, C(O)N(C.sub.1-6 alkyl)Cy.sup.7A, or C(O)N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.7A, or [0081] R.sup.8 is Cy.sup.8A, OCy.sup.8A, O(C.sub.1-3 alkylenyl)Cy.sup.8A, C(O)OCy.sup.8A, C(O)O(C.sub.1-3 alkylenyl)Cy.sup.8A, NHCy.sup.8A, NH(C.sub.1-3 alkylenyl)Cy.sup.8A, N(C.sub.1-6 alkyl)Cy.sup.8A, N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.8A, C(O)NHCy.sup.8A, C(O)NH(C.sub.1-3 alkylenyl)Cy.sup.8A, C(O)N(C.sub.1-6 alkyl)Cy.sup.8A, or C(O)N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.8A.

[0082] The present disclosure provides, inter alia, a compound of Formula (I):

##STR00004##

[0083] or a pharmaceutically acceptable salt thereof, wherein:

[0084] L.sup.1 is absent, or a group of formula N(R.sup.N) or C(O);

[0085] D is a group of formula (D1), (D2), (D3), (D4), (D5), (D6), or (D7):

##STR00005##

[0086] m is 1, 2 or 3;

[0087] A.sup.1 is C(O)R.sup.1, S(O).sub.2R.sup.1, NHC(O)R.sup.1, (C.sub.1-3 alkylene)-C(O)R.sup.1, NH(C.sub.1-3 alkylene)-C(O)R.sup.1, CN, NO.sub.2, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, (C.sub.1-3 alkylene)-5-10 membered heteroaryl, or (C.sub.1-3 alkylene)-4-10 membered heterocycloalkyl, wherein the (C.sub.1-3 alkylene) group of the (C.sub.1-3 alkylene)-C(O)R.sup.1 group forming A.sup.1 is unsubstituted or substituted by 1, 2, 3, 4 or 5 substituents each independently selected from halogen, OR.sup.a1, NR.sup.c1R.sup.d1, NR.sup.a1(CO)(C.sub.1-6 alkyl), and NR.sup.a1(CO)O(C.sub.1-6 alkyl); and wherein the 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, (C.sub.1-3 alkylene)-5-10 membered heteroaryl, or (C.sub.1-3 alkylene)-4-10 membered heterocycloalkyl forming A.sup.1 is unsubstituted or substituted by 1, 2, 3, 4 or 5 substituents each independently selected from halogen, OR.sup.a1, SR.sup.a1, C(O)OR.sup.a1, NR.sup.c1R.sup.d1 and C(O)NR.sup.c1R.sup.d1;

[0088] L.sup.2 is absent, or a group of formula N(R.sup.N), O, or C(O);

[0089] L.sup.3 is absent or a group of formula CH.sub.2, C≡C, N(R.sup.N) or C(O);

[0090] each R.sup.N is independently H, C.sub.1-6 alkyl, C(O)C.sub.1-6 alkyl, or C(O)OC.sub.1-6 alkyl;

[0091] R.sup.1 is H, C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, Cy.sup.1A, OH, OC.sub.1-6 alkyl, OCy.sup.1A, O(C.sub.1-3 alkylenyl)Cy.sup.1A, NH.sub.2, NHC.sub.1-6 alkyl, N(C.sub.1-6 alkyl).sub.2, NHCy.sup.1A, NH(C.sub.1-3 alkylenyl)Cy.sup.1A, N(C.sub.1-6 alkyl)Cy.sup.1A, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.1A, wherein each of the C.sub.1-6 alkyl forming R.sup.1 is unsubstituted or substituted by 1, 2, 3, 4 or 5 substituents each independently selected from halogen, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1;

[0092] Cy.sup.1A is C.sub.6-10 aryl, C.sub.3-15 cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkyl, wherein each of the C.sub.6-10 aryl, C.sub.3-15 cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkyl forming Cy.sup.1A is unsubstituted or substituted by 0, 1 or 2 Cy.sup.1B and 0, 1, 2, 3, 4 or 5 substituents each independently selected from unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1 and C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1;

[0093] each Cy.sup.1B is C.sub.6-10 aryl, C.sub.3-15 cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkyl, wherein each of the C.sub.6-10 aryl, C.sub.3-15 cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkyl forming Cy.sup.1B is unsubstituted or substituted by 1, 2, 3, 4 or 5 substituents each independently selected from unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1; and C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1;

[0094] A.sup.2 is CR.sup.2 or N;

[0095] A.sup.3 is CR.sup.3 or N;

[0096] A.sup.4 is CR.sup.4 or N;

[0097] A.sup.5 is CR.sup.5 or N;

[0098] A.sup.6 is CR.sup.6 or N;

[0099] A.sup.7 is CR.sup.7 or N;

[0100] A.sup.8 is CR.sup.8 or N;

[0101] A.sup.9 is CR.sup.9 or N;

[0102] A.sup.10 is CR.sup.10 or N;

[0103] A.sup.D41 is CH, C(C.sub.1-6 alkyl) or N;

[0104] A.sup.D42 is CH.sub.2, NH or NC.sub.1-6 alkyl;

[0105] R.sup.2 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, C(O)OR.sup.a1, C(O)NR.sup.c1R.sup.d1 or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1;

[0106] R.sup.3 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, C(O)OR.sup.a1, C(O)NR.sup.c1R.sup.d1 or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1;

[0107] R.sup.4 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, C(O)OR.sup.a1, C(O)NR.sup.c1R.sup.d1 or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1;

[0108] R.sup.5 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, C(O)OR.sup.a1, C(O)NR.sup.c1R.sup.d1 or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1;

[0109] R.sup.6 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, C(O)OR.sup.a1, C(O)NR.sup.c1R.sup.d1 or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1;

[0110] R.sup.7 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, C(O)OR.sup.a1, C(O)NR.sup.c1R.sup.d1, Cy.sup.7A, OCy.sup.7A, O(C.sub.1-3 alkylenyl)Cy.sup.7A, C(O)OCy.sup.7A, C(O)O(C.sub.1-3 alkylenyl)Cy.sup.7A, NHCy.sup.7A, NH(C.sub.1-3 alkylenyl)Cy.sup.7A, N(C.sub.1-6 alkyl)Cy.sup.7A, N(C(O)C.sub.1-6 alkyl)Cy.sup.7A, N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.7A, C(O)NHCy.sup.7A, C(O)NH(C.sub.1-3 alkylenyl)Cy.sup.7A, C(O)N(C.sub.1-6 alkyl)Cy.sup.7A, C(O)N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.7A or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1;

[0111] Cy.sup.7A is C.sub.6-10 aryl, C.sub.3-15 cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkyl, wherein each of the C.sub.6-10 aryl, C.sub.3-15 cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkyl forming Cy.sup.7A is unsubstituted or substituted by 0, 1 or 2 substituents selected from Cy.sup.7B, OCy.sup.7B, NHCy.sup.7B, and C(O)NHCy.sup.7B, and 0, 1, 2, 3, 4 or 5 substituents each independently selected from unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, C(O)OR.sup.a1, C(O)NR.sup.c1R.sup.d1, and C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1;

[0112] each Cy.sup.7B is C.sub.6-10 aryl, C.sub.3-15 cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkyl, wherein each of the C.sub.6-10 aryl, C.sub.3-15 cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkyl forming Cy.sup.7B is unsubstituted or substituted by 1, 2, 3, 4 or 5 substituents each independently selected from unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, C(O)OR.sup.a1, C(O)NR.sup.c1R.sup.d1, and C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1;

[0113] R.sup.8 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, C(O)OR.sup.a1, C(O)NR.sup.c1R.sup.d1, Cy.sup.8A, OH, OCy.sup.8A, O(C.sub.1-3 alkylenyl)Cy.sup.8A, C(O)OCy.sup.8A, C(O)O(C.sub.1-3 alkylenyl)Cy.sup.8A, NHCy.sup.8A, N(Cy.sup.8A).sub.2, NH(C.sub.1-3 alkylenyl)Cy.sup.8A, N(C.sub.1-6 alkyl)Cy.sup.8A, N(C(O)C.sub.1-6 alkyl)Cy.sup.8A, SO.sub.2NHCy.sup.8A, N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.8A, C(O)NHCy.sup.8A, C.sub.1-3 alkylene-C(O)NHCy.sup.8A, C(O)NH(C.sub.1-3 alkylenyl)Cy.sup.8A, C(O)N(C.sub.1-6 alkyl)Cy.sup.8A, C(O)N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.8A, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1;

[0114] Cy.sup.8A is C.sub.6-10 aryl, C.sub.3-15 cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkyl, wherein each of the C.sub.6-10 aryl, C.sub.3-15 cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkyl forming Cy.sup.8A is unsubstituted or substituted by 0, 1 or 2 substituents selected from Cy.sup.8B, OCy.sup.8B, NHCy.sup.8B, and C(O)NHCy.sup.8B, and 0, 1, 2, 3, 4 or 5 substituents each independently selected from unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, C(O)OR.sup.a1, C(O)NR.sup.c1R.sup.d1, and C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1;

[0115] each Cy.sup.8B is C.sub.6-10 aryl, C.sub.3-15 cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkyl, wherein each of the C.sub.6-10 aryl, C.sub.3-15 cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkyl forming Cy.sup.8B is unsubstituted or substituted by 1, 2, 3, 4 or 5 substituents each independently selected from unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, C(O)OR.sup.a1, C(O)NR.sup.c1R.sup.d1, and C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1;

[0116] R.sup.9 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, C(O)OR.sup.a1, C(O)NR.sup.c1R.sup.d1, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1;

[0117] R.sup.10 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, C(O)OR.sup.a1, C(O)NR.sup.c1R.sup.d1, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1;

[0118] Cy.sup.D71 is C.sub.6-10 aryl, C.sub.3-15 cycloalkyl, 5-14 membered heteroaryl, or 4-10 membered heterocycloalkyl, wherein each of the C.sub.6-10 aryl, C.sub.3-15 cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkyl forming Cy.sup.D71 is unsubstituted or substituted by 0, 1 or 2 substituents selected from Cy.sup.D72, CH.sub.2Cy.sup.D72, OCy.sup.D72, NHCy.sup.D72, O—C.sub.1-6 alkylene-Cy.sup.D72, N(C.sub.1-6 alkyl)Cy.sup.D72, N(C(O)C.sub.1-6 alkyl)Cy.sup.D72, and C(O)NHCy.sup.D72, and 0, 1, 2, 3, 4 or 5 substituents each independently selected from unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, C(O)OR.sup.a1, C(O)NR.sup.c1R.sup.d1, and C.sub.1-6 alkyl or C.sub.2-6 alkenyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, C(O)OR.sup.a1, and NR.sup.c1R.sup.d1;

[0119] each Cy.sup.D72 is C.sub.6-10 aryl, C.sub.3-15 cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkyl, wherein each of the C.sub.6-10 aryl, C.sub.3-15 cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkyl forming Cy.sup.D72 is unsubstituted or substituted by 1, 2, 3, 4 or 5 substituents each independently selected from unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, C.sub.3-15 cycloalkyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, C(O)OR.sup.a1, C(O)NR.sup.c1R.sup.d1, and C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, C(O)OR.sup.a1, and NR.sup.c1R.sup.d1; and

[0120] R.sup.a1, R.sup.b1, R.sup.c1 and R.sup.d1 are each independently selected from H, C.sub.1-6 alkyl, HO—C.sub.1-6 alkylene, C.sub.1-6 alkoxy-C.sub.1-6 alkylene, C.sub.6-10 aryl, C.sub.2-6 alkenyl and C.sub.2-6 alkynyl; or

[0121] R.sup.c1 and R.sup.d1 together with the nitrogen atom to which they are both attached together form a 4-10 membered unsubstituted heterocycloalkyl ring;

[0122] In some embodiments:

[0123] L.sup.1 is a group of formula N(R.sup.N) when L.sup.2 is C(O);

[0124] L.sup.1 is a group of formula C(O) when L.sup.2 is N(R.sup.N);

[0125] L.sup.2 is absent, or a group of formula N(R.sup.N) when L.sup.1 is C(O);

[0126] L.sup.2 is absent, or a group of formula C(O) when L.sup.1 is N(R.sup.N);

[0127] A.sup.D41 is CH, C(C.sub.1-6 alkyl) when A.sup.D42 is NH or NC.sub.1-6 alkyl;

[0128] A.sup.D42 is CH.sub.2 when A.sup.D41 is NH or NC.sub.1-6 alkyl;

[0129] no more than two of A.sup.2, A.sup.3, A.sup.4 and A.sup.5 is N;

[0130] no more than two of A.sup.6, A.sup.7, A.sup.8, A.sup.9 and A.sup.10 is N; and

[0131] either R.sup.1 is present and is Cy.sup.1A, OCy.sup.1A, O(C.sub.1-3 alkylenyl)Cy.sup.1A, NHCy.sup.1A NH(C.sub.1-3 alkylenyl)Cy.sup.1A, N(C.sub.1-6 alkyl)Cy.sup.1A, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.1A; or

[0132] R.sup.7 is Cy.sup.7A, OCy.sup.7A, O(C.sub.1-3 alkylenyl)Cy.sup.7A C(O)OCy.sup.7A, C(O)O(C.sub.1-3 alkylenyl)Cy.sup.7A, NHCy.sup.7A, NH(C.sub.1-3 alkylenyl)Cy.sup.7A, N(C.sub.1-6 alkyl)Cy.sup.7A, N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.7A; C(O)NHCy.sup.7A, C(O)NH(C.sub.1-3 alkylenyl)Cy.sup.7A, C(O)N(C.sub.1-6 alkyl)Cy.sup.7A, or C(O)N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.7A, or

[0133] R.sup.8 is Cy.sup.8A, OCy.sup.8A, O(C.sub.1-3 alkylenyl)Cy.sup.8A, C(O)OCy.sup.8A, C(O)O(C.sub.1-3 alkylenyl)Cy.sup.8A, NHCy.sup.8A, NH(C.sub.1-3 alkylenyl)Cy.sup.8A, N(C.sub.1-6 alkyl)Cy.sup.8A, N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.8A, C(O)NHCy.sup.8A, C(O)NH(C.sub.1-3 alkylenyl)Cy.sup.8A, C(O)N(C.sub.1-6 alkyl)Cy.sup.8A, or C(O)N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.8A.

[0134] In some embodiments, L.sup.1 is absent.

[0135] In some embodiments, L.sup.1 is N(R.sup.N), e.g., NH or NMe.

[0136] In some embodiments, L.sup.1 is C(O).

[0137] In some embodiments, D is a group of formula (D1).

[0138] In some embodiments, D is a group of formula (D2).

[0139] In some embodiments, D is a group of formula (D3).

[0140] In some embodiments, D is a group of formula (D4).

[0141] In some embodiments, D is a group of formula (D5).

[0142] In some embodiments, D is a group of formula (D6).

[0143] In some embodiments, D is a group of formula (D7).

[0144] In some embodiments, A.sup.1 is C(O)R.sup.1, e.g., C(O)OH.

[0145] In some embodiments, A.sup.1 is S(O).sub.2R.sup.1.

[0146] In some embodiments, A.sup.1 is NHC(O)R.sup.1.

[0147] In some embodiments, A.sup.1 is NH(C.sub.1-3 alkylene)-C(O)R.sup.1.

[0148] In some embodiments, wherein A.sup.1 is (C.sub.1-3 alkylene)-C(O)R.sup.1, wherein the (C.sub.1-3 alkylene) group of the (C.sub.1-3 alkylene)-C(O)R.sup.1 group forming A.sup.1 is unsubstituted or substituted by 0, 1, 2, 3, 4 or 5 substituents each independently selected from halogen, OR.sup.a1, NR.sup.c1R.sup.d1, NR.sup.a1(CO)(C.sub.1-6 alkyl), and NR.sup.a1(CO)O(C.sub.1-6 alkyl).

[0149] In some embodiments, A.sup.1 is (C.sub.1-3 alkylene)-C(O)R.sup.1, wherein the (C.sub.1-3 alkylene) group of the (C.sub.1-3 alkylene)-C(O)R.sup.1 group forming A.sup.1 is substituted by NR.sup.c1R.sup.d1, NR.sup.a1(CO)(C.sub.1-6 alkyl), or NR.sup.a1(CO)O(C.sub.1-6 alkyl), e.g., CH.sub.2CH(NH.sub.2)C(O)OH.

[0150] In some embodiments, A.sup.1 is CN.

[0151] In some embodiments, A.sup.1 is NO.sub.2.

[0152] In some embodiments, A.sup.1 is 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, (C.sub.1-3 alkylene)-5-10 membered heteroaryl, or (C.sub.1-3 alkylene)-4-10 membered heterocycloalkyl that is unsubstituted or substituted by 0, 1, 2, 3, 4 or 5 substituents each independently selected from halogen, OR.sup.a1, SR.sup.a1, C(O)OR.sup.a1, NR.sup.c1R.sup.d1 and C(O)NR.sup.c1R.sup.d1.

[0153] In some embodiments, A.sup.1 is 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, CH.sub.2(5-10 membered heteroaryl), or CH.sub.2(4-10 membered heterocycloalkyl) that is unsubstituted or substituted by 1, 2, 3, 4 or 5 substituents each independently selected from halogen, OR.sup.a1, SR.sup.a1, C(O)OR.sup.a1, NR.sup.c1R.sup.d1 and C(O)NR.sup.c1R.sup.d1.

[0154] In some embodiments, A.sup.2 is CR.sup.2.

[0155] In some embodiments, R.sup.2 is H.

[0156] In some embodiments, A.sup.2 is N.

[0157] In some embodiments, A.sup.3 is CR.sup.3.

[0158] In some embodiments, R.sup.3 is H, C.sub.1-6 alkyl or C.sub.1-6 haloalkyl.

[0159] In some embodiments, R.sup.3 is H, methyl or trifluoroethyl.

[0160] In some embodiments, R.sup.3 is H.

[0161] In some embodiments, A.sup.3 is N.

[0162] In some embodiments, A.sup.4 is CR.sup.4.

[0163] In some embodiments, R.sup.4 is H.

[0164] In some embodiments, A.sup.4 is N.

[0165] In some embodiments, A.sup.5 is CR.sup.5.

[0166] In some embodiments, R.sup.5 is H.

[0167] In some embodiments, A.sup.5 is N.

[0168] In some embodiments, A.sup.2 is CR.sup.2, A.sup.3 is CR.sup.3, A.sup.4 is CR.sup.4, and A.sup.5 is CR.sup.5.

[0169] In some embodiments, A.sup.2 is CR.sup.2, A.sup.3 is CR.sup.3, A.sup.4 is CR.sup.4, and A.sup.5 is N.

[0170] In some embodiments, D is a group of formula (D4).

[0171] In some embodiments, A.sup.D41 is CH

[0172] In some embodiments, A.sup.D41 is C(C.sub.1-6 alkyl).

[0173] In some embodiments, A.sup.D41 is N.

[0174] In some embodiments, A.sup.D42 is NH.

[0175] In some embodiments, A.sup.D42 is NC.sub.1-6 alkyl, e.g., NMe.

[0176] In some embodiments, A.sup.D42 is CH.sub.2.

[0177] In some embodiments, D is a group of formula (D4) and m is 1.

[0178] In some embodiments, D is a group of formula (D4) and m is 2.

[0179] In some embodiments, D is a group of formula (D4) and m is 3.

[0180] In some embodiments, D is a group of formula (D5).

[0181] In some embodiments, D is a group of formula (D5) and m is 1.

[0182] In some embodiments, D is a group of formula (D5) and m is 2.

[0183] In some embodiments, D is a group of formula (D5) and m is 3.

[0184] In some embodiments, D is a group of formula (D6).

[0185] In some embodiments, D is a group of formula (D6) and m is 1.

[0186] In some embodiments, D is a group of formula (D6) and m is 2.

[0187] In some embodiments, D is a group of formula (D6) and m is 3.

[0188] In some embodiments, D is a group of formula (D7).

[0189] In some embodiments, L.sup.2 is absent.

[0190] In some embodiments, L.sup.2 is a group of formula O.

[0191] In some embodiments, L.sup.2 is a group of formula N(R.sup.N).

[0192] In some embodiments, L.sup.2 is a group of formula C(O).

[0193] In some embodiments, L.sup.3 is absent.

[0194] In some embodiments, L.sup.3 is a group of formula CH.sub.2.

[0195] In some embodiments, L.sup.3 is a group of formula N(R.sup.N).

[0196] In some embodiments, L.sup.3 is a group of formula C(O).

[0197] In some embodiments, L.sup.3 is a group of formula C≡C.

[0198] In some embodiments, Cy.sup.D71 is C.sub.6-10 aryl (e.g., phenyl).

[0199] In some embodiments, Cy.sup.D71 is C.sub.3-15 cycloalkyl (e.g., cyclopropyl).

[0200] In some embodiments, Cy.sup.D71 is 5-10 membered heteroaryl (e.g., triazol, pyridine, dihydropyrido[2,1-b]pyrimidin-2-one, 3,4-dihydroquinolin-2-one, benzo[d]isothiazole-1,1-dioxide, 2H-indazole, pyrazole, dioxolane, pyrrole, indole, imidazole, benzimidazole).

[0201] In some embodiments, Cy.sup.D71 is 4-10 membered heterocycloalkyl (e.g., piperidine, 1,3-dioxolane, indoline, pyrrolidine).

[0202] In some embodiments, the C.sub.6-10 aryl, C.sub.3-15 cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkyl forming Cy.sup.D71 is unsubstituted.

[0203] In some embodiments, the C.sub.6-10 aryl, C.sub.3-15 cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkyl forming Cy.sup.D71 is substituted.

[0204] In some embodiments, the C.sub.6-10 aryl, C.sub.3-15 cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkyl forming Cy.sup.D71 is substituted by 1, 2, 3, 4 or 5 substituents each independently selected from unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, C(O)OR.sup.a1, C(O)NR.sup.c1R.sup.d1, and C.sub.1-6 alkyl or C.sub.2-6 alkenyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, C(O)OR.sup.a1, and NR.sup.c1R.sup.d1.

[0205] In some embodiments, the C.sub.6-10 aryl, C.sub.3-15 cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkyl forming Cy.sup.D71 is substituted by 0, 1 or 2 substituents selected from Cy.sup.D72, CH.sub.2Cy.sup.D72, OCy.sup.D72, NHCy.sup.D72, O—C.sub.1-6 alkylene-Cy.sup.D72, N(C.sub.1-6 alkyl)Cy.sup.D72, N(C(O)C.sub.1-6 alkyl)Cy.sup.D72, and C(O)NHCy.sup.D72.

[0206] In some embodiments, Cy.sup.D72 is C.sub.6-10 aryl (e.g., phenyl).

[0207] In some embodiments, Cy.sup.D72 is C.sub.3-15 cycloalkyl (e.g., cyclopropyl).

[0208] In some embodiments, Cy.sup.D72 is 5-10 membered heteroaryl (e.g., triazol, pyridine, dihydropyrido[2,1-b]pyrimidin-2-one, 3,4-dihydroquinolin-2-one, benzo[d]isothiazole-1,1-dioxide, 2H-indazole, pyrazole, dioxolane, pyrrole, indole, imidazole, benzimidazole).

[0209] In some embodiments, Cy.sup.D72 is 4-10 membered heterocycloalkyl (e.g., piperidine, 1,3-dioxolane, indoline, pyrrolidine).

[0210] In some embodiments, the C.sub.6-10 aryl, C.sub.3-15 cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkyl forming Cy.sup.D72 is unsubstituted.

[0211] In some embodiments, the C.sub.6-10 aryl, C.sub.3-15 cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkyl forming Cy.sup.D72 is substituted.

[0212] In some embodiments, the C.sub.6-10 aryl, C.sub.3-15 cycloalkyl, 5-10 membered heteroaryl, or 4-10 membered heterocycloalkyl forming Cy.sup.D72 is substituted by 0, 1 or 2 substituents selected from C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, C.sub.3-15 cycloalkyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, C(O)OR.sup.a1, C(O)NR.sup.c1R.sup.d1, and C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, C(O)OR.sup.a1, and NR.sup.c1R.sup.d1.

[0213] In some embodiments, R.sup.1 is H, C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, Cy.sup.1A, OH, OC.sub.1-6 alkyl, OCy.sup.1A, O(C.sub.1-3 alkylenyl)Cy.sup.1A, NH.sub.2, NHC.sub.1-6 alkyl, N(C.sub.1-6 alkyl).sub.2, NHCy.sup.1A, NH(C.sub.1-3 alkylenyl)Cy.sup.1A, N(C.sub.1-6 alkyl)Cy.sup.1A, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.1A.

[0214] In some embodiments, R.sup.1 is Cy.sup.1A, OCy.sup.1A, O(C.sub.1-3 alkylenyl)Cy.sup.1A, NHCy.sup.1A NH(C.sub.1-3 alkylenyl)Cy.sup.1A, N(C.sub.1-6 alkyl)Cy.sup.1A, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.1A.

[0215] In some embodiments, R.sup.1 is NHCy.sup.1A.

[0216] In some embodiments, R.sup.1 is C.sub.1-6 alkyl (e.g., methyl), C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, Cy.sup.1AOH, or OC.sub.1-6 alkyl (e.g., OMe).

[0217] In some embodiments, R.sup.1 is OH.

[0218] In some embodiments, R.sup.1 is a group of one of the following formulae:

##STR00006##

[0219] wherein:

[0220] R.sup.11 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.1B, OH, OCy.sup.1B, O(C.sub.1-3 alkylenyl)Cy.sup.1B, NHCy.sup.1B, NH(C.sub.1-3 alkylenyl)Cy.sup.1B, N(C.sub.1-6 alkyl)Cy.sup.1B, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.1B, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1;

[0221] R.sup.12 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.1B, OH, OCy.sup.1B, O(C.sub.1-3 alkylenyl)Cy.sup.1B, NHCy.sup.1B, NH(C.sub.1-3 alkylenyl)Cy.sup.1B, N(C.sub.1-6 alkyl)Cy.sup.1B, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.1B, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1;

[0222] R.sup.13 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.1B, OH, OCy.sup.1B, O(C.sub.1-3 alkylenyl)Cy.sup.1B, NHCy.sup.1B, NH(C.sub.1-3 alkylenyl)Cy.sup.1B, N(C.sub.1-6 alkyl)Cy.sup.1B, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.1B, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1;

[0223] R.sup.14 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.1B, OH, OCy.sup.1B, O(C.sub.1-3 alkylenyl)Cy.sup.1B, NHCy.sup.1B, NH(C.sub.1-3 alkylenyl)Cy.sup.1B, N(C.sub.1-6 alkyl)Cy.sup.1B, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.1B, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1;

[0224] R.sup.15 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.1B, OH, OCy.sup.1B, O(C.sub.1-3 alkylenyl)Cy.sup.1B, NHCy.sup.1B, NH(C.sub.1-3 alkylenyl)Cy.sup.1B, N(C.sub.1-6 alkyl)Cy.sup.1B, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.1B, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1;

[0225] R.sup.16 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.1B, OH, OCy.sup.1B, O(C.sub.1-3 alkylenyl)Cy.sup.1B, NHCy.sup.1B, NH(C.sub.1-3 alkylenyl)Cy.sup.1B, N(C.sub.1-6 alkyl)Cy.sup.1B, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.1B, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1;

[0226] R.sup.17 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.1B, OH, OCy.sup.1B, O(C.sub.1-3 alkylenyl)Cy.sup.1B, NHCy.sup.1B, NH(C.sub.1-3 alkylenyl)Cy.sup.1B, N(C.sub.1-6 alkyl)Cy.sup.1B, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.1B, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1; and

[0227] R.sup.18 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.1B, OH, OCy.sup.1B, O(C.sub.1-3 alkylenyl)Cy.sup.1B, NHCy.sup.1B, NH(C.sub.1-3 alkylenyl)Cy.sup.1B, N(C.sub.1-6 alkyl)Cy.sup.1B, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.1B, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1.

[0228] In some embodiments, R.sup.1 is a group of one of the following formulae:

##STR00007##

[0229] In some embodiments, Cy.sup.1A is C.sub.6-10 aryl, e.g., phenyl that is unsubstituted or substituted by 0, 1 or 2 Cy.sup.1B and 0, 1, 2, 3, 4 or 5 substituents each independently selected from unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1 and C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1.

[0230] In some embodiments, Cy.sup.1A is C.sub.6-10 aryl, e.g., phenyl that is unsubstituted or substituted by 1 Cy.sup.1B and 0, 1, 2, 3, 4 or 5 substituents each independently selected from unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1 and C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1.

[0231] In some embodiments, Cy.sup.1A is C.sub.6-10 aryl, e.g., phenyl that is unsubstituted or substituted by 1 Cy.sup.1B.

[0232] In some embodiments, each Cy.sup.1B is C.sub.3-15 cycloalkyl (e.g., C.sub.3-10 cycloalkyl, e.g., adamantyl, e.g., adamant-1-yl) that is unsubstituted or substituted by 1, 2, 3, 4 or 5 substituents each independently selected from unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1 and C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1.

[0233] In some embodiments, each Cy.sup.1B is unsubstituted C.sub.3-15 cycloalkyl (e.g., C.sub.3-10 cycloalkyl, e.g., adamantyl, e.g., adamant-1-yl).

[0234] In some embodiments, Cy.sup.1A is a group of one of the following formulae:

##STR00008##

[0235] wherein

[0236] R.sup.11 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.1B, OH, OCy.sup.1B, O(C.sub.1-3 alkylenyl)Cy.sup.1B, NHCy.sup.1B, NH(C.sub.1-3 alkylenyl)Cy.sup.1B, N(C.sub.1-6 alkyl)Cy.sup.1B, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.1B, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1;

[0237] R.sup.12 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.1B, OH, OCy.sup.1B, O(C.sub.1-3 alkylenyl)Cy.sup.1B, NHCy.sup.1B, NH(C.sub.1-3 alkylenyl)Cy.sup.1B, N(C.sub.1-6 alkyl)Cy.sup.1B, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.1B, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1;

[0238] R.sup.13 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.1B, OH, OCy.sup.1B, O(C.sub.1-3 alkylenyl)Cy.sup.1B, NHCy.sup.1B, NH(C.sub.1-3 alkylenyl)Cy.sup.1B, N(C.sub.1-6 alkyl)Cy.sup.1B, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.1B, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1;

[0239] R.sup.14 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.1B, OH, OCy.sup.1B, O(C.sub.1-3 alkylenyl)Cy.sup.1B, NHCy.sup.1B, NH(C.sub.1-3 alkylenyl)Cy.sup.1B, N(C.sub.1-6 alkyl)Cy.sup.1B, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.1B, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1;

[0240] R.sup.15 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.1B, OH, OCy.sup.1B, O(C.sub.1-3 alkylenyl)Cy.sup.1B, NHCy.sup.1B, NH(C.sub.1-3 alkylenyl)Cy.sup.1B, N(C.sub.1-6 alkyl)Cy.sup.1B, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.1B, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1;

[0241] R.sup.16 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.1B, OH, OCy.sup.1B, O(C.sub.1-3 alkylenyl)Cy.sup.1B, NHCy.sup.1B, NH(C.sub.1-3 alkylenyl)Cy.sup.1B, N(C.sub.1-6 alkyl)Cy.sup.1B, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.1B, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1;

[0242] R.sup.17 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.1B, OH, OCy.sup.1B, O(C.sub.1-3 alkylenyl)Cy.sup.1B, NHCy.sup.1B, NH(C.sub.1-3 alkylenyl)Cy.sup.1B, N(C.sub.1-6 alkyl)Cy.sup.1B, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.1B, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1; and

[0243] R.sup.18 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.1B, OH, OCy.sup.1B, O(C.sub.1-3 alkylenyl)Cy.sup.1B, NHCy.sup.1B, NH(C.sub.1-3 alkylenyl)Cy.sup.1B, N(C.sub.1-6 alkyl)Cy.sup.1B, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.1B, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1.

[0244] In some embodiments, Cy.sup.1A is a group of one of the following formulae:

##STR00009##

[0245] In some embodiments, Cy.sup.1A is C.sub.3-15 cycloalkyl (e.g., C.sub.3-10 cycloalkyl, e.g., adamantyl, e.g., adamant-1-yl) that is unsubstituted or substituted by 0, 1 or 2 Cy.sup.1B and 0, 1, 2, 3, 4 or 5 substituents each independently selected from unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1 and C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1. In some embodiments, Cy.sup.1A is C.sub.3-15 cycloalkyl (e.g., C.sub.3-10 cycloalkyl, e.g., adamantyl, e.g., adamant-1-yl) that is unsubstituted or substituted by 1, 2, 3, 4 or 5 substituents each independently selected from unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1 and C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1 In some embodiments, Cy.sup.1A is unsubstituted C.sub.3-15 cycloalkyl (e.g., C.sub.3-10 cycloalkyl, e.g., adamantyl, e.g., adamant-1-yl). In some embodiments, Cy.sup.1A is adamantyl, e.g., adamant-1-yl that is unsubstituted or substituted. In some embodiments, Cy.sup.1A is unsubstituted adamantyl, e.g., adamant-1-yl.

[0246] In some embodiments: [0247] R.sup.7 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1 or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1; and [0248] R.sup.8 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1 or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1.

[0249] In some embodiments, R.sup.7 is H and R.sup.8 is H.

[0250] In some embodiments, L.sup.2 is absent.

[0251] In some embodiments, L.sup.2 is N(R.sup.N).

[0252] In some embodiments, L.sup.2 is C(O).

[0253] In some embodiments, R.sup.N is H.

[0254] In some embodiments, A.sup.6 is CR.sup.6.

[0255] In some embodiments, R.sup.6 is H.

[0256] In some embodiments, A.sup.6 is N.

[0257] In some embodiments, A.sup.7 is CR.sup.7.

[0258] In some embodiments, R.sup.7 is H.

[0259] In some embodiments, R.sup.7 is Cy.sup.7A, OCy.sup.7A, O(C.sub.1-3 alkylenyl)Cy.sup.7A, C(O)OCy.sup.7A, C(O)O(C.sub.1-3 alkylenyl)Cy.sup.7A, NHCy.sup.7A, NH(C.sub.1-3 alkylenyl)Cy.sup.7A, N(C.sub.1-6 alkyl)Cy.sup.7A, N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.7A; C(O)NHCy.sup.7A, C(O)NH(C.sub.1-3 alkylenyl)Cy.sup.7A, C(O)N(C.sub.1-6 alkyl)Cy.sup.7A, or C(O)N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.7A.

[0260] In some embodiments, R.sup.7 is Cy.sup.7A, OCy.sup.7A, O(C.sub.1-3 alkylenyl)Cy.sup.7A, NHCy.sup.7A, NH(C.sub.1-3 alkylenyl)Cy.sup.7A, N(C.sub.1-6 alkyl)Cy.sup.7A, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.7A.

[0261] In some embodiments, R.sup.7 is N(C(O)C.sub.1-6 alkyl)Cy.sup.7A.

[0262] In some embodiments, R.sup.7 is NHCy.sup.7A.

[0263] In some embodiments, R.sup.7 is a group of one of the following formulae:

##STR00010##

[0264] wherein:

[0265] R.sup.71 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.7B, OH, OCy.sup.7B, O(C.sub.1-3 alkylenyl)Cy.sup.7B, NHCy.sup.7B, NH(C.sub.1-3 alkylenyl)Cy.sup.7B, N(C.sub.1-6 alkyl)Cy.sup.7B, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.7B, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1;

[0266] R.sup.72 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.7B, OH, OCy.sup.7B, O(C.sub.1-3 alkylenyl)Cy.sup.7B, NHCy.sup.7B, NH(C.sub.1-3 alkylenyl)Cy.sup.7B, N(C.sub.1-6 alkyl)Cy.sup.7B, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.7B, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1;

[0267] R.sup.73 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.7B, OH, OCy.sup.7B, O(C.sub.1-3 alkylenyl)Cy.sup.7B, NHCy.sup.7B, NH(C.sub.1-3 alkylenyl)Cy.sup.7B, N(C.sub.1-6 alkyl)Cy.sup.7B, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.7B, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1;

[0268] R.sup.74 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.7B, OH, OCy.sup.7B, O(C.sub.1-3 alkylenyl)Cy.sup.7B, NHCy.sup.7B, NH(C.sub.1-3 alkylenyl)Cy.sup.7B, N(C.sub.1-6 alkyl)Cy.sup.7B, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.7B, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1;

[0269] R.sup.75 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.7B, OH, OCy.sup.7B, O(C.sub.1-3 alkylenyl)Cy.sup.7B, NHCy.sup.7B, NH(C.sub.1-3 alkylenyl)Cy.sup.7B, N(C.sub.1-6 alkyl)Cy.sup.7B, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.7B, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1;

[0270] R.sup.76 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.7B, OH, OCy.sup.7B, O(C.sub.1-3 alkylenyl)Cy.sup.7B, NHCy.sup.7B, NH(C.sub.1-3 alkylenyl)Cy.sup.7B, N(C.sub.1-6 alkyl)Cy.sup.7B, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.7B, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1;

[0271] R.sup.77 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.7B, OH, OCy.sup.7B, O(C.sub.1-3 alkylenyl)Cy.sup.7B, NHCy.sup.7B, NH(C.sub.1-3 alkylenyl)Cy.sup.7B, N(C.sub.1-6 alkyl)Cy.sup.7B, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.7B, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1; and

[0272] R.sup.78 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.7B, OH, OCy.sup.7B, O(C.sub.1-3 alkylenyl)Cy.sup.7B, NHCy.sup.7B, NH(C.sub.1-3 alkylenyl)Cy.sup.7B, N(C.sub.1-6 alkyl)Cy.sup.7B, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.7B, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1.

[0273] In some embodiments, R.sup.7 is a group of one of the following formulae:

##STR00011##

[0274] In some embodiments, Cy.sup.7A is C.sub.6-10 aryl, e.g., phenyl that is unsubstituted or substituted by 0, 1 or 2 Cy.sup.7B and 0, 1, 2, 3, 4 or 5 substituents each independently selected from unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, and C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1.

[0275] In some embodiments, Cy.sup.7A is C.sub.6-10 aryl, e.g., phenyl that is unsubstituted or substituted by 1 Cy.sup.7B and 0, 1, 2, 3, 4 or 5 substituents each independently selected from unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, and C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1.

[0276] In some embodiments, Cy.sup.7A is C.sub.6-10 aryl, e.g., phenyl that is unsubstituted or substituted by 1 Cy.sup.7B.

[0277] In some embodiments, each Cy.sup.7B is C.sub.3-15 cycloalkyl (e.g., C.sub.3-10 cycloalkyl, e.g., adamantyl, e.g., adamant-1-yl) that is unsubstituted or substituted by 1, 2, 3, 4 or 5 substituents each independently selected from unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, and C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1.

[0278] In some embodiments, each Cy.sup.7B is unsubstituted C.sub.3-15 cycloalkyl (e.g., C.sub.3-10 cycloalkyl, e.g., adamantyl, e.g., adamant-1-yl).

[0279] In some embodiments, Cy.sup.7A is a group of one of the following formulae:

##STR00012##

[0280] wherein:

[0281] R.sup.71 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.8B, OH, OCy.sup.8B, O(C.sub.1-3 alkylenyl)Cy.sup.8B, NHCy.sup.8B, NH(C.sub.1-3 alkylenyl)Cy.sup.8B, N(C.sub.1-6 alkyl)Cy.sup.8B, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.8B, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1;

[0282] R.sup.72 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.8B, OH, OCy.sup.8B, O(C.sub.1-3 alkylenyl)Cy.sup.8B, NHCy.sup.8B, NH(C.sub.1-3 alkylenyl)Cy.sup.8B, N(C.sub.1-6 alkyl)Cy.sup.8B, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.8B, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1;

[0283] R.sup.73 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.8B, OH, OCy.sup.8B, O(C.sub.1-3 alkylenyl)Cy.sup.8B, NHCy.sup.8B, NH(C.sub.1-3 alkylenyl)Cy.sup.8B, N(C.sub.1-6 alkyl)Cy.sup.8B, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.8B, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1;

[0284] R.sup.74 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.8B, OH, OCy.sup.8B, O(C.sub.1-3 alkylenyl)Cy.sup.8B, NHCy.sup.8B, NH(C.sub.1-3 alkylenyl)Cy.sup.8B, N(C.sub.1-6 alkyl)Cy.sup.8B, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.8B, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1;

[0285] R.sup.75 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.8B, OH, OCy.sup.8B, O(C.sub.1-3 alkylenyl)Cy.sup.8B, NHCy.sup.8B, NH(C.sub.1-3 alkylenyl)Cy.sup.8B, N(C.sub.1-6 alkyl)Cy.sup.8B, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.8B, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1;

[0286] R.sup.76 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.8B, OH, OCy.sup.8B, O(C.sub.1-3 alkylenyl)Cy.sup.8B, NHCy.sup.8B, NH(C.sub.1-3 alkylenyl)Cy.sup.8B, N(C.sub.1-6 alkyl)Cy.sup.8B, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.8B, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1;

[0287] R.sup.77 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.8B, OH, OCy.sup.8B, O(C.sub.1-3 alkylenyl)Cy.sup.8B, NHCy.sup.8B, NH(C.sub.1-3 alkylenyl)Cy.sup.8B, N(C.sub.1-6 alkyl)Cy.sup.8B, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.8B, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1; and

[0288] R.sup.78 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.8B, OH, OCy.sup.8B, O(C.sub.1-3 alkylenyl)Cy.sup.8B, NHCy.sup.8B, NH(C.sub.1-3 alkylenyl)Cy.sup.8B, N(C.sub.1-6 alkyl)Cy.sup.8B, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.8B, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1.

[0289] In some embodiments, Cy.sup.7A is a group of one of the following formulae:

##STR00013##

[0290] In some embodiments, Cy.sup.7A is C.sub.3-15 cycloalkyl (e.g., C.sub.3-10 cycloalkyl, e.g., adamantyl, e.g., adamant-1-yl) that is unsubstituted or substituted by 0, 1 or 2 Cy.sup.7B and 0, 1, 2, 3, 4 or 5 substituents each independently selected from unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1 and C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1. In some embodiments, Cy.sup.7A is C.sub.3-15 cycloalkyl (e.g., C.sub.3-10 cycloalkyl, e.g., adamantyl, e.g., adamant-1-yl) that is unsubstituted or substituted by 01, 2, 3, 4 or 5 substituents each independently selected from unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1 and C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1 In some embodiments, Cy.sup.7A is unsubstituted C.sub.3-15 cycloalkyl (e.g., C.sub.3-10 cycloalkyl, e.g., adamantyl, e.g., adamant-1-yl). In some embodiments, Cy.sup.7A is adamantyl, e.g., adamant-1-yl that is unsubstituted or substituted. In some embodiments, Cy.sup.7A is unsubstituted adamantyl, e.g., adamant-1-yl.

[0291] In some embodiments: [0292] R.sup.1 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1 or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1; and [0293] R.sup.8 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1 or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1.

[0294] In some embodiments, A.sup.1 is CR.sup.1, A.sup.2 is CR.sup.2, A.sup.3 is CR.sup.3, A.sup.4 is CR.sup.4, A.sup.5 is CR.sup.5, A.sup.6 is CR.sup.6, A.sup.8 is CR.sup.8, A.sup.9 is CR.sup.9, and A.sup.10 is CR.sup.10.

[0295] In some embodiments, A.sup.1 is CR.sup.1, A.sup.3 is CR.sup.3, A.sup.4 is CR.sup.4, A.sup.5 is N, A.sup.6 is CR.sup.6, A.sup.8 is CR.sup.8, A.sup.9 is CR.sup.9, and A.sup.10 is CR.sup.10.

[0296] In some embodiments, A.sup.7 is N.

[0297] In some embodiments, A.sup.8 is CR.sup.8.

[0298] In some embodiments, R.sup.8 is H.

[0299] In some embodiments, R.sup.8 is Cy.sup.8A, OCy.sup.8A, O(C.sub.1-3 alkylenyl)Cy.sup.8A, C(O)OCy.sup.8A, C(O)O(C.sub.1-3 alkylenyl)Cy.sup.8A, NHCy.sup.8A, NH(C.sub.1-3 alkylenyl)Cy.sup.8A, N(C.sub.1-6 alkyl)Cy.sup.8A, N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.8A, C(O)NHCy.sup.8A, C(O)NH(C.sub.1-3 alkylenyl)Cy.sup.8A, C(O)N(C.sub.1-6 alkyl)Cy.sup.8A, or C(O)N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.8A.

[0300] In some embodiments, R.sup.8 is Cy.sup.8A, OCy.sup.8A, O(C.sub.1-3 alkylenyl)Cy.sup.8A, NHCy.sup.8A, NH(C.sub.1-3 alkylenyl)Cy.sup.8A, N(C.sub.1-6 alkyl)Cy.sup.8A, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.8A.

[0301] In some embodiments, R.sup.8 is N(Cy.sup.8A).sub.2.

[0302] In some embodiments, R.sup.8 is N(C(O)C.sub.1-6 alkyl)Cy.sup.8A.

[0303] In some embodiments, R.sup.8 is SO.sub.2NHCy.sup.8A.

[0304] In some embodiments, R.sup.8 is C.sub.1-3 alkylene-C(O)NHCy.sup.8A.

[0305] In some embodiments, R.sup.8 is NHCy.sup.8A.

[0306] In some embodiments, R.sup.8 is a group of one of the following formulae:

##STR00014##

[0307] wherein:

[0308] R.sup.81 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.8A, OH, OCy.sup.8A, O(C.sub.1-3 alkylenyl)Cy.sup.8A, NHCy.sup.8A, NH(C.sub.1-3 alkylenyl)Cy.sup.8A, N(C.sub.1-6 alkyl)Cy.sup.8A, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.8A, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1;

[0309] R.sup.82 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.8A, OH, OCy.sup.8A, O(C.sub.1-3 alkylenyl)Cy.sup.8A, NHCy.sup.8A, NH(C.sub.1-3 alkylenyl)Cy.sup.8A, N(C.sub.1-6 alkyl)Cy.sup.8A, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.8A, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1;

[0310] R.sup.83 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.8A, OH, OCy.sup.8A, O(C.sub.1-3 alkylenyl)Cy.sup.8A, NHCy.sup.8A, NH(C.sub.1-3 alkylenyl)Cy.sup.8A, N(C.sub.1-6 alkyl)Cy.sup.8A, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.8A, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1;

[0311] R.sup.84 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.8A, OH, OCy.sup.8A, O(C.sub.1-3 alkylenyl)Cy.sup.8A, NHCy.sup.8A, NH(C.sub.1-3 alkylenyl)Cy.sup.8A, N(C.sub.1-6 alkyl)Cy.sup.8A, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.8A, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1;

[0312] R.sup.85 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.8A, OH, OCy.sup.8A, O(C.sub.1-3 alkylenyl)Cy.sup.8A, NHCy.sup.8A, NH(C.sub.1-3 alkylenyl)Cy.sup.8A, N(C.sub.1-6 alkyl)Cy.sup.8A, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.8A, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1;

[0313] R.sup.86 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.8A, OH, OCy.sup.8A, O(C.sub.1-3 alkylenyl)Cy.sup.8A, NHCy.sup.8A, NH(C.sub.1-3 alkylenyl)Cy.sup.8A, N(C.sub.1-6 alkyl)Cy.sup.8A, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.8A, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1;

[0314] R.sup.87 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.8A, OH, OCy.sup.8A, O(C.sub.1-3 alkylenyl)Cy.sup.8A, NHCy.sup.8A, NH(C.sub.1-3 alkylenyl)Cy.sup.8A, N(C.sub.1-6 alkyl)Cy.sup.8A, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.8A, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1; and

[0315] R.sup.88 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.8A, OH, OCy.sup.8A, O(C.sub.1-3 alkylenyl)Cy.sup.8A, NHCy.sup.8A, NH(C.sub.1-3 alkylenyl)Cy.sup.8A, N(C.sub.1-6 alkyl)Cy.sup.8A, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.8A, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1.

[0316] In some embodiments, R.sup.8 is a group of one of the following formulae:

##STR00015##

[0317] In some embodiments, Cy.sup.8A is C.sub.6-10 aryl, e.g., phenyl that is unsubstituted or substituted by 0, 1 or 2 Cy.sup.8B and 0, 1, 2, 3, 4 or 5 substituents each independently selected from unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1 and C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1.

[0318] In some embodiments, Cy.sup.8A is C.sub.6-10 aryl, e.g., phenyl that is unsubstituted or substituted by 1 Cy.sup.8B and 0, 1, 2, 3, 4 or 5 substituents each independently selected from unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, and C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1.

[0319] In some embodiments, Cy.sup.8A is C.sub.6-10 aryl, e.g., phenyl that is unsubstituted or substituted by 1 Cy.sup.8B.

[0320] In some embodiments, each Cy.sup.8B is C.sub.3-15 cycloalkyl (e.g., C.sub.3-10 cycloalkyl, e.g., adamantyl, e.g., adamant-1-yl) that is unsubstituted or substituted by 1, 2, 3, 4 or 5 substituents each independently selected from unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1 and C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1.

[0321] In some embodiments, each Cy.sup.8B is unsubstituted C.sub.3-15 cycloalkyl (e.g., C.sub.3-10 cycloalkyl, e.g., adamantyl, e.g., adamant-1-yl).

[0322] In some embodiments, Cy.sup.8A is a group of one of the following formulae:

##STR00016##

[0323] wherein:

[0324] R.sup.81 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.8A, OH, OCy.sup.8A, O(C.sub.1-3 alkylenyl)Cy.sup.8A, NHCy.sup.8A, NH(C.sub.1-3 alkylenyl)Cy.sup.8A, N(C.sub.1-6 alkyl)Cy.sup.8A, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.8A, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1;

[0325] R.sup.82 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.8A, OH, OCy.sup.8A, O(C.sub.1-3 alkylenyl)Cy.sup.8A, NHCy.sup.8A, NH(C.sub.1-3 alkylenyl)Cy.sup.8A, N(C.sub.1-6 alkyl)Cy.sup.8A, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.8A, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1;

[0326] R.sup.83 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.8A, OH, OCy.sup.8A, O(C.sub.1-3 alkylenyl)Cy.sup.8A, NHCy.sup.8A, NH(C.sub.1-3 alkylenyl)Cy.sup.8A, N(C.sub.1-6 alkyl)Cy.sup.8A, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.8A, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1;

[0327] R.sup.84 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.8A, OH, OCy.sup.8A, O(C.sub.1-3 alkylenyl)Cy.sup.8A, NHCy.sup.8A, NH(C.sub.1-3 alkylenyl)Cy.sup.8A, N(C.sub.1-6 alkyl)Cy.sup.8A, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.8A, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1;

[0328] R.sup.85 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.8A, OH, OCy.sup.8A, O(C.sub.1-3 alkylenyl)Cy.sup.8A, NHCy.sup.8A, NH(C.sub.1-3 alkylenyl)Cy.sup.8A, N(C.sub.1-6 alkyl)Cy.sup.8A, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.8A, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1;

[0329] R.sup.86 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.8A, OH, OCy.sup.8A, O(C.sub.1-3 alkylenyl)Cy.sup.8A, NHCy.sup.8A, NH(C.sub.1-3 alkylenyl)Cy.sup.8A, N(C.sub.1-6 alkyl)Cy.sup.8A, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.8A, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1;

[0330] R.sup.87 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.8A, OH, OCy.sup.8A, O(C.sub.1-3 alkylenyl)Cy.sup.8A, NHCy.sup.8A, NH(C.sub.1-3 alkylenyl)Cy.sup.8A, N(C.sub.1-6 alkyl)Cy.sup.8A, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.8A, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1; and

[0331] R.sup.88 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.8A, OH, OCy.sup.8A, O(C.sub.1-3 alkylenyl)Cy.sup.8A, NHCy.sup.8A, NH(C.sub.1-3 alkylenyl)Cy.sup.8A, N(C.sub.1-6 alkyl)Cy.sup.8A, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.8A, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1.

[0332] In some embodiments, Cy.sup.8A is a group of one of the following formulae:

##STR00017##

[0333] In some embodiments, Cy.sup.8A is C.sub.3-15 cycloalkyl (e.g., C.sub.3-10 cycloalkyl, e.g., adamantyl, e.g., adamant-1-yl) that is unsubstituted or substituted by 0, 1 or 2 Cy.sup.8B and 0, 1, 2, 3, 4 or 5 substituents each independently selected from unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1 and C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1. In some embodiments, Cy.sup.8A is C.sub.3-15 cycloalkyl (e.g., C.sub.3-10 cycloalkyl, e.g., adamantyl, e.g., adamant-1-yl) that is unsubstituted or substituted by 01, 2, 3, 4 or 5 substituents each independently selected from unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1 and C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1 In some embodiments, Cy.sup.8A is unsubstituted C.sub.3-15 cycloalkyl (e.g., C.sub.3-10 cycloalkyl, e.g., adamantyl, e.g., adamant-1-yl). In some embodiments, Cy.sup.8A is adamantyl, e.g., adamant-1-yl that is unsubstituted or substituted. In some embodiments, Cy.sup.8A is unsubstituted adamantyl, e.g., adamant-1-yl.

[0334] In some embodiments: [0335] R.sup.1 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1 or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1; and [0336] R.sup.7 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1 or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1.

[0337] In some embodiments, A.sup.1 is CR.sup.1, A.sup.2 is CR.sup.2, A.sup.3 is CR.sup.3, A.sup.4 is CR.sup.4, A.sup.5 is CR.sup.5, A.sup.6 is CR.sup.6, A.sup.7 is CR.sup.7, A.sup.8 is CR.sup.8, A.sup.9 is CR.sup.9, and A.sup.10 is CR.sup.10.

[0338] In some embodiments, A.sup.1 is CR.sup.1, A.sup.3 is CR.sup.3, A.sup.4 is CR.sup.4, A.sup.5 is N, A.sup.6 is CR.sup.6, A.sup.7 is CR.sup.7, A.sup.8 is CR.sup.8, A.sup.9 is CR.sup.9, and A.sup.10 is CR.sup.10.

[0339] In some embodiments, A.sup.8 is N.

[0340] In some embodiments, A.sup.9 is CR.sup.9.

[0341] In some embodiments, R.sup.9 is H, C.sub.1-6 alkyl or C.sub.1-6 haloalkyl.

[0342] In some embodiments, R.sup.9 is H, methyl or trifluoroethyl.

[0343] In some embodiments, R.sup.9 is H.

[0344] In some embodiments, A.sup.9 is N.

[0345] In some embodiments, A.sup.10 is CR.sup.10.

[0346] In some embodiments, R.sup.10 is H.

[0347] In some embodiments, A.sup.10 is N.

[0348] In some embodiments, the compound is a compound of one of the following formulae (I-1) to (I-60):

##STR00018## ##STR00019## ##STR00020## ##STR00021## ##STR00022## ##STR00023## ##STR00024## ##STR00025## ##STR00026## ##STR00027## ##STR00028## ##STR00029##

[0349] wherein:

[0350] R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.8, R.sup.9, R.sup.10, R.sup.N, A.sup.1, A.sup.2, A.sup.3, A.sup.4, A.sup.5, A.sup.6, A.sup.7, A.sup.8, A.sup.9, A.sup.10, Cy.sup.1A, Cy.sup.1B, Cy.sup.7A, Cy.sup.7B, Cy.sup.8A, Cy.sup.8B, L.sup.1 and L.sup.2, are as defined above for the compounds of formula (I), or any of the embodiments thereof;

[0351] L.sup.7 is absent, O, NH or N(C.sub.1-6 alkyl);

[0352] L.sup.8 is absent, O, NH or N(C.sub.1-6 alkyl);

[0353] R.sup.11 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.1B, OH, OCy.sup.1B, O(C.sub.1-3 alkylenyl)Cy.sup.1B, NHCy.sup.1B, NH(C.sub.1-3 alkylenyl)Cy.sup.1B, N(C.sub.1-6 alkyl)Cy.sup.1B, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.1B, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1;

[0354] R.sup.12 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.1B, OH, OCy.sup.1B, O(C.sub.1-3 alkylenyl)Cy.sup.1B, NHCy.sup.1B, NH(C.sub.1-3 alkylenyl)Cy.sup.1B, N(C.sub.1-6 alkyl)Cy.sup.1B, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.1B, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1;

[0355] R.sup.13 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.1B, OH, OCy.sup.1B, O(C.sub.1-3 alkylenyl)Cy.sup.1B, NHCy.sup.1B, NH(C.sub.1-3 alkylenyl)Cy.sup.1B, N(C.sub.1-6 alkyl)Cy.sup.1B, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.1B, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1;

[0356] R.sup.14 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.1B, OH, OCy.sup.1B, O(C.sub.1-3 alkylenyl)Cy.sup.1B, NHCy.sup.1B, NH(C.sub.1-3 alkylenyl)Cy.sup.1B, N(C.sub.1-6 alkyl)Cy.sup.1B, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.1B, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1;

[0357] R.sup.15 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.1B, OH, OCy.sup.1B, O(C.sub.1-3 alkylenyl)Cy.sup.1B, NHCy.sup.1B, NH(C.sub.1-3 alkylenyl)Cy.sup.1B, N(C.sub.1-6 alkyl)Cy.sup.1B, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.1B, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1;

[0358] R.sup.16 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.1B, OH, OCy.sup.1B, O(C.sub.1-3 alkylenyl)Cy.sup.1B, NHCy.sup.1B, NH(C.sub.1-3 alkylenyl)Cy.sup.1B, N(C.sub.1-6 alkyl)Cy.sup.1B, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.1B, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1;

[0359] R.sup.17 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.1B, OH, OCy.sup.1B, O(C.sub.1-3 alkylenyl)Cy.sup.1B, NHCy.sup.1B, NH(C.sub.1-3 alkylenyl)Cy.sup.1B, N(C.sub.1-6 alkyl)Cy.sup.1B, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.1B, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1;

[0360] R.sup.18 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.1B, OH, OCy.sup.1B, O(C.sub.1-3 alkylenyl)Cy.sup.1B, NHCy.sup.1B, NH(C.sub.1-3 alkylenyl)Cy.sup.1B, N(C.sub.1-6 alkyl)Cy.sup.1B, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.1B, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1;

[0361] R.sup.71 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.7B, OH, OCy.sup.7B, O(C.sub.1-3 alkylenyl)Cy.sup.7B, NHCy.sup.7B, NH(C.sub.1-3 alkylenyl)Cy.sup.7B, N(C.sub.1-6 alkyl)Cy.sup.7B, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.7B, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1;

[0362] R.sup.72 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.7B, OH, OCy.sup.7B, O(C.sub.1-3 alkylenyl)Cy.sup.7B, NHCy.sup.7B, NH(C.sub.1-3 alkylenyl)Cy.sup.7B, N(C.sub.1-6 alkyl)Cy.sup.7B, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.7B, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1;

[0363] R.sup.73 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.7B, OH, OCy.sup.7B, O(C.sub.1-3 alkylenyl)Cy.sup.7B, NHCy.sup.7B, NH(C.sub.1-3 alkylenyl)Cy.sup.7B, N(C.sub.1-6 alkyl)Cy.sup.7B, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.7B, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1;

[0364] R.sup.74 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.7B, OH, OCy.sup.7B, O(C.sub.1-3 alkylenyl)Cy.sup.7B, NHCy.sup.7B, NH(C.sub.1-3 alkylenyl)Cy.sup.7B, N(C.sub.1-6 alkyl)Cy.sup.7B, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.7B, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1;

[0365] R.sup.75 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.7B, OH, OCy.sup.7B, O(C.sub.1-3 alkylenyl)Cy.sup.7B, NHCy.sup.7B, NH(C.sub.1-3 alkylenyl)Cy.sup.7B, N(C.sub.1-6 alkyl)Cy.sup.7B, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.7B, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1;

[0366] R.sup.76 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.7B, OH, OCy.sup.7B, O(C.sub.1-3 alkylenyl)Cy.sup.7B, NHCy.sup.7B, NH(C.sub.1-3 alkylenyl)Cy.sup.7B, N(C.sub.1-6 alkyl)Cy.sup.7B, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.7B, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1;

[0367] R.sup.77 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.7B, OH, OCy.sup.7B, O(C.sub.1-3 alkylenyl)Cy.sup.7B, NHCy.sup.7B, NH(C.sub.1-3 alkylenyl)Cy.sup.7B, N(C.sub.1-6 alkyl)Cy.sup.7B, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.7B, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1; and

[0368] R.sup.78 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.7B, OH, OCy.sup.7B, O(C.sub.1-3 alkylenyl)Cy.sup.7B, NHCy.sup.7B, NH(C.sub.1-3 alkylenyl)Cy.sup.7B, N(C.sub.1-6 alkyl)Cy.sup.7B, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.7B, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1;

[0369] R.sup.81 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.8B, OH, OCy.sup.8B, O(C.sub.1-3 alkylenyl)Cy.sup.8B, NHCy.sup.8B, NH(C.sub.1-3 alkylenyl)Cy.sup.8B, N(C.sub.1-6 alkyl)Cy.sup.8B, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.8B, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1;

[0370] R.sup.82 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.8B, OH, OCy.sup.8B, O(C.sub.1-3 alkylenyl)Cy.sup.8B, NHCy.sup.8B, NH(C.sub.1-3 alkylenyl)Cy.sup.8B, N(C.sub.1-6 alkyl)Cy.sup.8B, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.8B, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1;

[0371] R.sup.83 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.8B, OH, OCy.sup.8B, O(C.sub.1-3 alkylenyl)Cy.sup.8B, NHCy.sup.8B, NH(C.sub.1-3 alkylenyl)Cy.sup.8B, N(C.sub.1-6 alkyl)Cy.sup.8B, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.8B, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1;

[0372] R.sup.84 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.8B, OH, OCy.sup.8B, O(C.sub.1-3 alkylenyl)Cy.sup.8B, NHCy.sup.8B, NH(C.sub.1-3 alkylenyl)Cy.sup.8B, N(C.sub.1-6 alkyl)Cy.sup.8B, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.8B, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1;

[0373] R.sup.85 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.8B, OH, OCy.sup.8B, O(C.sub.1-3 alkylenyl)Cy.sup.8B, NHCy.sup.8B, NH(C.sub.1-3 alkylenyl)Cy.sup.8B, N(C.sub.1-6 alkyl)Cy.sup.8B, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.8B, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1;

[0374] R.sup.86 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.8B, OH, OCy.sup.8B, O(C.sub.1-3 alkylenyl)Cy.sup.8B, NHCy.sup.8B, NH(C.sub.1-3 alkylenyl)Cy.sup.8B, N(C.sub.1-6 alkyl)Cy.sup.8B, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.8B, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1;

[0375] R.sup.87 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.8B, OH, OCy.sup.8B, O(C.sub.1-3 alkylenyl)Cy.sup.8B, NHCy.sup.8B, NH(C.sub.1-3 alkylenyl)Cy.sup.8B, N(C.sub.1-6 alkyl)Cy.sup.8B, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.8B, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1; and

[0376] R.sup.88 is H, unsubstituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl, C.sub.2-6 alkynyl, halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, NR.sup.c1R.sup.d1, Cy.sup.8B, OH, OCy.sup.8B, O(C.sub.1-3 alkylenyl)Cy.sup.8B, NHCy.sup.8B, NH(C.sub.1-3 alkylenyl)Cy.sup.8B, N(C.sub.1-6 alkyl)Cy.sup.8B, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.8B, or C.sub.1-6 alkyl that is substituted by 1, 2, or 3 substituents each independently selected from halogen, C.sub.1-6 haloalkyl, CN, OR.sup.a1, SR.sup.a1, and NR.sup.c1R.sup.d1.

[0377] In some embodiments, R.sup.1 is OH.

[0378] In some embodiments, R.sup.1 is OC.sub.1-6 alkyl (e.g., OMe).

[0379] In some embodiments, R.sup.1 is C.sub.2-6 alkenyl (e.g., vinyl).

[0380] In some embodiments, L.sup.7 is NH.

[0381] In some embodiments, L.sup.8 is NH.

[0382] In some embodiments, R.sup.a1, R.sup.b1, R.sup.c1 and R.sup.d1 are each independently selected from H, C.sub.1-6 alkyl, HO—C.sub.1-6 alkylene, C.sub.1-6 alkoxy-C.sub.1-6 alkylene, C.sub.6-10 aryl, C.sub.2-6 alkenyl and C.sub.2-6 alkynyl.

[0383] In some embodiments, the compound is a compound of one of the following formulae, or a pharmaceutically acceptable salt thereof:

##STR00030## ##STR00031## ##STR00032## ##STR00033## ##STR00034## ##STR00035## ##STR00036## ##STR00037## ##STR00038## ##STR00039## ##STR00040## ##STR00041## ##STR00042## ##STR00043## ##STR00044## ##STR00045## ##STR00046## ##STR00047## ##STR00048## ##STR00049## ##STR00050## ##STR00051## ##STR00052## ##STR00053## ##STR00054##

##STR00055## ##STR00056## ##STR00057## ##STR00058## ##STR00059## ##STR00060## ##STR00061## ##STR00062## ##STR00063## ##STR00064## ##STR00065## ##STR00066## ##STR00067## ##STR00068## ##STR00069## ##STR00070## ##STR00071## ##STR00072## ##STR00073## ##STR00074## ##STR00075## ##STR00076## ##STR00077## ##STR00078## ##STR00079##

[0384] In some embodiments, the compound is a compound of one of the following formulae, or a pharmaceutically acceptable salt thereof:

##STR00080## ##STR00081## ##STR00082## ##STR00083## ##STR00084## ##STR00085## ##STR00086## ##STR00087## ##STR00088## ##STR00089## ##STR00090## ##STR00091##

[0385] The compounds, or any of the embodiments thereof, can be provided in the form of a composition such as a pharmaceutical composition that includes the compound, or a salt such as a pharmaceutically acceptable salt thereof, and at least one additional agent such as a pharmaceutically acceptable carrier.

[0386] It is further appreciated that certain features of the invention, which are, for clarity, described in the context of separate embodiments, can also be provided in combination in a single embodiment (while the embodiments are intended to be combined as if written in multiply dependent form). Conversely, various features of the invention which are, for brevity, described in the context of a single embodiment, can also be provided separately or in any suitable subcombination. Thus, it is contemplated that features described as embodiments of the compounds of Formula (I) can be combined in any suitable combination.

[0387] At various places in the present specification, certain features of the compounds are disclosed in groups or in ranges. It is specifically intended that such a disclosure include each and every individual subcombination of the members of such groups and ranges. For example, the term “C.sub.1-6 alkyl” is specifically intended to individually disclose (without limitation) methyl, ethyl, C.sub.3 alkyl, C.sub.4 alkyl, C.sub.5 alkyl and C.sub.6 alkyl.

[0388] The term “n-membered,” where n is an integer, typically describes the number of ring-forming atoms in a moiety where the number of ring-forming atoms is n. For example, piperidinyl is an example of a 6-membered heterocycloalkyl ring, pyrazolyl is an example of a 5-membered heteroaryl ring, pyridyl is an example of a 6-membered heteroaryl ring and 1,2,3,4-tetrahydro-naphthalene is an example of a 10-membered cycloalkyl group. When the term is used to refer to a carbocyclic ring (e.g., aryl or cycloalkyl), all of the ring atoms are carbon atoms. When the term is used to refer to a heterocyclic ring (e.g., heteroaryl or heterocycloalkyl), one or more of the ring atoms (e.g., 1, 2, 3, or 4) are heteroatoms (e.g., nitrogen, oxygen or sulfur) and the remainder (e.g., n−1, n−2, n−3, or n−4) are carbon atoms.

[0389] At various places in the present specification, variables defining divalent linking groups are described. It is specifically intended that each linking substituent include both the forward and backward forms of the linking substituent. For example, —NR(CR′R″).sub.n— includes both —NR(CR′R″).sub.n— and —(CR′R″).sub.nNR— and is intended to disclose each of the forms individually. Where the structure requires a linking group, the Markush variables listed for that group are understood to be linking groups. For example, if the structure requires a linking group and the Markush group definition for that variable lists “alkyl” or “aryl” then it is understood that the “alkyl” or “aryl” represents a linking alkylene group or arylene group, respectively.

[0390] The term “substituted” means that an atom or group of atoms formally replaces hydrogen as a “substituent” attached to another group. The term “substituted”, unless otherwise indicated, refers to any level of substitution, e.g., mono-, di-, tri-, tetra- or penta-substitution, where such substitution is permitted. The substituents are independently selected, and substitution may be at any chemically accessible position. It is to be understood that substitution at a given atom is limited by valency. The term “optionally substituted” means unsubstituted or substituted. The term “substituted” means that a hydrogen atom is removed and replaced by a substituent. A single divalent substituent, e.g., oxo, can replace two hydrogen atoms.

[0391] The term “Cn-m” indicates a range which includes the endpoints, wherein n and m are integers and indicate the number of carbons. Examples include C.sub.1-4, C.sub.1-6 and the like. Whenever the term is used intended to describe each member included in the group, C.sub.n through C.sub.m as if each had been explicitly set forth. For example, the term C.sub.1-6 is intended to describe each of the members C.sub.1, C.sub.2, C.sub.3, C.sub.4, C.sub.5 and C.sub.6.

[0392] The term “alkyl” employed alone or in combination with other terms, refers to a saturated hydrocarbon group that may be straight-chain or branched. The term “Cn-m alkyl”, refers to an alkyl group having n to m carbon atoms. An alkyl group formally corresponds to an alkane with one C—H bond replaced by the point of attachment of the alkyl group to the remainder of the compound. In some embodiments, the alkyl group contains from 1 to 6 carbon atoms, from 1 to 4 carbon atoms, from 1 to 3 carbon atoms, or 1 to 2 carbon atoms. Examples of alkyl moieties include, but are not limited to, chemical groups such as methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, isobutyl, sec-butyl; higher homologs such as 2-methyl-1-butyl, n-pentyl, 3-pentyl, n-hexyl, 1,2,2-trimethylpropyl and the like.

[0393] The term “alkenyl” employed alone or in combination with other terms, refers to a straight-chain or branched hydrocarbon group corresponding to an alkyl group having one or more double carbon-carbon bonds. An alkenyl group formally corresponds to an alkene with one C—H bond replaced by the point of attachment of the alkenyl group to the remainder of the compound. The term “Cn-m alkenyl” refers to an alkenyl group having n to m carbons. In some embodiments, the alkenyl moiety contains 2 to 6, 2 to 4, or 2 to 3 carbon atoms. Example alkenyl groups include, but are not limited to, ethenyl, n-propenyl, isopropenyl, n-butenyl, sec-butenyl and the like.

[0394] The term “alkynyl” employed alone or in combination with other terms, refers to a straight-chain or branched hydrocarbon group corresponding to an alkyl group having one or more triple carbon-carbon bonds. An alkynyl group formally corresponds to an alkyne with one C—H bond replaced by the point of attachment of the alkyl group to the remainder of the compound. The term “Cn-m alkynyl” refers to an alkynyl group having n to m carbons. Example alkynyl groups include, but are not limited to, ethynyl, propyn-1-yl, propyn-2-yl and the like. In some embodiments, the alkynyl moiety contains 2 to 6, 2 to 4, or 2 to 3 carbon atoms.

[0395] The term “alkylene”, employed alone or in combination with other terms, refers to a divalent alkyl linking group. An alkylene group formally corresponds to an alkane with two C—H bond replaced by points of attachment of the alkylene group to the remainder of the compound.

[0396] The term “Cn-m alkylene” refers to an alkylene group having n to m carbon atoms. Examples of alkylene groups include, but are not limited to, ethan-1,2-diyl, propan-1,3-diyl, propan-1,2-diyl, butan-1,4-diyl, butan-1,3-diyl, butan-1,2-diyl, 2-methyl-propan-1,3-diyl and the like.

[0397] The term “alkoxy”, employed alone or in combination with other terms, refers to a group of formula —O-alkyl, wherein the alkyl group is as defined above. The term “Cn-m alkoxy” refers to an alkoxy group, the alkyl group of which has n to m carbons. Example alkoxy groups include methoxy, ethoxy, propoxy (e.g., n-propoxy and isopropoxy), t-butoxy and the like. In some embodiments, the alkyl group has 1 to 6, 1 to 4, or 1 to 3 carbon atoms.

[0398] The terms “halo” or “halogen”, used alone or in combination with other terms, refers to fluoro, chloro, bromo and iodo.

[0399] The term “haloalkyl” refers to an alkyl group in which one or more of the hydrogen atoms has been replaced by a halogen atom. The term “C.sub.n-m haloalkyl” refers to a C.sub.n-m alkyl group having n to m carbon atoms and from at least one up to {2(n to m)+1} halogen atoms, which may either be the same or different. In some embodiments, the halogen atoms are fluoro atoms. In some embodiments, the haloalkyl group has 1 to 6 or 1 to 4 carbon atoms. Example haloalkyl groups include CF.sub.3, C.sub.2F.sub.5, CHF.sub.2, CCl.sub.3, CHCl.sub.2, C.sub.2Cl.sub.5 and the like. In some embodiments, the haloalkyl group is a fluoroalkyl group.

[0400] The term “haloalkoxy”, employed alone or in combination with other terms, refers to a group of formula —O-haloalkyl, wherein the haloalkyl group is as defined above. The term “C.sub.n-m haloalkoxy” refers to a haloalkoxy group, the haloalkyl group of which has n to m carbons. Example haloalkoxy groups include trifluoromethoxy and the like. In some embodiments, the haloalkoxy group has 1 to 6, 1 to 4, or 1 to 3 carbon atoms.

[0401] The term “amino” refers to a group of formula —NH.sub.2.

[0402] The term “carbamyl” refers to a group of formula —C(═O)NH.sub.2.

[0403] The term “carbonyl”, employed alone or in combination with other terms, refers to a —C(═O)— group, which also may be written as C(O).

[0404] The term “carbonyl”, employed alone or in combination with other terms, refers to a —C(═O)— group.

[0405] The term “carboxy” refers to a group of formula —C(═O)OH.

[0406] The term “oxo” refers to oxygen as a divalent substituent, forming a carbonyl group, or attached to a heteroatom forming a sulfoxide or sulfone group, or an N-oxide group.

[0407] The term “aromatic” refers to a carbocycle or heterocycle having one or more polyunsaturated rings having aromatic character (i.e., having (4n+2) delocalized 7r (pi) electrons where n is an integer).

[0408] The term “aryl,” employed alone or in combination with other terms, refers to an aromatic hydrocarbon group, which may be monocyclic or polycyclic (e.g., having 2, 3 or 4 fused rings). The term “Cn-m aryl” refers to an aryl group having from n to m ring carbon atoms. Aryl groups include, e.g., phenyl, naphthyl, indenyl and the like. In some embodiments, aryl groups have from 6 to 10 carbon atoms. In some embodiments, the aryl group is phenyl.

[0409] The term “arylalkylenyl,” employed alone or in combination with other terms, refers to an aryl group, as defined herein, attached to an alkylene group, as defined herein. The term “C.sub.n-m aryl C.sub.o-p alkylenyl” refers to an arylalkylenyl group with an aryl group having from n to m ring carbon atoms attached to an alkylene group having from o to p carbon atoms. Arylalkylenyl groups include, e.g., benzyl, phenethyl and the like.

[0410] The term “heteroaryl” or “heteroaromatic” employed alone or in combination with other terms, refers to a monocyclic or polycyclic aromatic heterocycle having at least one heteroatom ring member selected from sulfur, oxygen and nitrogen. In some embodiments, the heteroaryl is a 5- or 6-membered monocyclic heteroaryl ring. In some embodiments, the heteroaryl is 5- to 10-membered C.sub.1-9 heteroaryl, which is monocyclic or bicyclic and which has 1, 2, 3 or 4 heteroatom ring members independently selected from nitrogen, sulfur and oxygen. In some embodiments, any ring-forming N in a heteroaryl moiety can be an N-oxide. In some embodiments, the heteroaryl has 5-10 ring atoms including carbon atoms and 1, 2, 3 or 4 heteroatom ring members independently selected from nitrogen, sulfur and oxygen. In some embodiments, the heteroaryl has 5-6 ring atoms and 1, 2, 3, or 4 heteroatom ring members independently selected from nitrogen, sulfur and oxygen. In some embodiments, the heteroaryl has 5-6 ring atoms and 1 or 2 heteroatom ring members independently selected from nitrogen, sulfur and oxygen. In some embodiments, the heteroaryl is a five-membered or six-membered heteroaryl ring. Example heteroaryl groups include, but are not limited to, pyridine, pyrimidine, pyrazine, pyridazine, pyrrole, pyrazole, azolyl, oxazole, thiazole, imidazole, furan, thiophene, quinoline, isoquinoline, indole, benzothiophene, benzofuran, benzisoxazole, imidazo[1,2-b]thiazole, imidazo[1,2-b]pyridazine, purine, furopyridine (e.g., furo[3,2-b]pyridine), thienopyridine (e.g. thieno[3,2-b]pyridine) or the like.

[0411] A five-membered heteroaryl ring is a heteroaryl group having five ring atoms wherein one or more (e.g., 1, 2, 3 or 4) ring atoms are independently selected from N, O and S. Exemplary five-membered ring heteroaryls include thienyl, furyl, pyrrolyl, imidazolyl, thiazolyl, oxazolyl, pyrazolyl, isothiazolyl, isoxazolyl, 1,2,3-triazolyl, tetrazolyl, 1,2,3-thiadiazolyl, 1,2,3-oxadiazolyl, 1,2,4-triazolyl, 1,2,4-thiadiazolyl, 1,2,4-oxadiazolyl, 1,3,4-triazolyl, 1,3,4-thiadiazolyl and 1,3,4-oxadiazolyl.

[0412] A six-membered heteroaryl ring is a heteroaryl group having six ring atoms wherein one or more (e.g., 1, 2 or 3) ring atoms are independently selected from N, O and S. Exemplary six-membered ring heteroaryls are pyridyl, pyrazinyl, pyrimidinyl, triazinyl and pyridazinyl.

[0413] The term “heteroarylalkylenyl,” employed alone or in combination with other terms, refers to heteroaryl group, as defined herein, attached to an alkylene group, as defined herein. The term “n-m membered heteroaryl C.sub.o-p alkylenyl” refers to a heteroaryl group having from n to m ring atoms attached to an alkylene group having from o to p carbon atoms. Heteroarylalkylenyl groups include, e.g., pyridylmethyl, pyridylethyl and the like.

[0414] The term “cycloalkyl”, employed alone or in combination with other terms, refers to a non-aromatic, saturated, monocyclic, bicyclic or polycyclic hydrocarbon ring system, including cyclized alkyl and alkenyl groups. The term “Cn-m cycloalkyl” refers to a cycloalkyl that has n to m ring member carbon atoms. Cycloalkyl groups can include mono- or polycyclic (e.g., having 2, 3 or 4 fused rings) groups and spirocycles. Cycloalkyl groups can have, e.g., 3, 4, 5, 6, 7, 8, 9 or 10 ring-forming carbons (C.sub.3-10) or 3, 4, 5, 6 or 7 ring-forming carbons (C.sub.3-7). In some embodiments, the cycloalkyl group has 3 to 6 ring members, 3 to 5 ring members, or 3 to 4 ring members. In some embodiments, the cycloalkyl group is monocyclic. In some embodiments, the cycloalkyl group is monocyclic or bicyclic. In some embodiments, the cycloalkyl group is a C.sub.3-6 monocyclic cycloalkyl group. Ring-forming carbon atoms of a cycloalkyl group can be optionally substituted by oxo or sulfido. Cycloalkyl groups also include cycloalkylidenes. Example cycloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopentenyl, cyclohexenyl, cyclohexadienyl, norbornyl, norpinyl, bicyclo[2.1.1]hexanyl, bicyclo[1.1.1]pentanyl, adamantyl and the like. In some embodiments, cycloalkyl is cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl. Also included in the definition of cycloalkyl are moieties that have one or more aromatic rings fused (i.e., having a bond in common with) to the cycloalkyl ring, e.g., benzo or thienyl derivatives of cyclopentane, cyclohexane and the like, for example indanyl or tetrahydronaphthyl. A cycloalkyl group containing a fused aromatic ring can be attached through any ring-forming atom including a ring-forming atom of the fused aromatic ring.

[0415] The term “arylalkylenyl,” employed alone or in combination with other terms, refers to a cycloalkyl group, as defined herein, attached to an alkylene group, as defined herein. The term “Cn-m cycloalkyl C.sub.o-p alkylenyl” refers to an cycloalkylalkylenyl group with a cycloalkyl group having from n to m ring carbon atoms attached to an alkylene group having from o to p carbon atoms. Cycloalkylalkylenyl groups include, e.g., cyclopropylmethyl, cyclopropylethyl, cyclobutylmethyl, cyclohexylmethyl, and the like.

[0416] The term “heterocycloalkyl”, employed alone or in combination with other terms, refers to non-aromatic ring or ring system, which may optionally contain one or more alkenylene groups as part of the ring structure, which has at least one heteroatom ring member independently selected from nitrogen, sulfur oxygen and phosphorus, and which has 4-10 ring members, 4-7 ring members or 4-6 ring members. Included in heterocycloalkyl are monocyclic 4-, 5-, 6- and 7-membered heterocycloalkyl groups. Heterocycloalkyl groups can include mono- or bicyclic (e.g., having two fused or bridged rings) ring systems. In some embodiments, the heterocycloalkyl group is a monocyclic group having 1, 2 or 3 heteroatoms independently selected from nitrogen, sulfur and oxygen. Examples of heterocycloalkyl groups include azetidine, pyrrolidine, piperidine, piperazine, morpholine, thiomorpholine, pyran, azepane, tetrahydropyran, tetrahydrofuran, dihydropyran, dihydrofuran and the like. Ring-forming carbon atoms and heteroatoms of a heterocycloalkyl group can be optionally substituted by oxo or sulfido (e.g., C(═O), S(═O), C(S) or S(═O).sub.2, etc.) or a nitrogen atom can be quaternized. The heterocycloalkyl group can be attached through a ring-forming carbon atom or a ring-forming heteroatom. In some embodiments, the heterocycloalkyl group contains 0 to 3 double bonds. In some embodiments, the heterocycloalkyl group contains 0 to 2 double bonds. Also included in the definition of heterocycloalkyl are moieties that have one or more aromatic rings fused (i.e., having a bond in common with) to the heterocycloalkyl ring, e.g., benzo or thienyl derivatives of piperidine, morpholine, azepine, etc. A heterocycloalkyl group containing a fused aromatic ring can be attached through any ring-forming atom including a ring-forming atom of the fused aromatic ring. Examples of heterocycloalkyl groups include 1, 2, 3, 4-tetrahydroquinoline, dihydrobenzofuran, azetidine, azepane, diazepan (e.g., 1,4-diazepan), pyrrolidine, piperidine, piperazine, morpholine, thiomorpholine, pyran, tetrahydrofuran and di- and tetra-hydropyran.

[0417] The term “heterocycloalkylalkylenyl,” employed alone or in combination with other terms, refers to heterocycloalkyl group, as defined herein, attached to an alkylene group, as defined herein. The term “n-m membered heterocycloalkyl C.sub.o-p alkylenyl” refers to a heterocycloalkyl group having from n to m ring atoms attached to an alkylene group having from o to p carbon atoms. Heteroarylalkylenyl groups include, e.g., tetrahydrofurylmethyl.

[0418] At certain places, the definitions or embodiments refer to specific rings (e.g., an azetidine ring, a pyridine ring, etc.). Unless otherwise indicated, these rings can be attached to any ring member provided that the valency of the atom is not exceeded. For example, an azetidine ring may be attached at any position of the ring, whereas an azetidin-3-yl ring is attached at the 3-position.

[0419] The compounds described herein can be asymmetric (e.g., having one or more stereocenters). All stereoisomers, such as enantiomers and diastereoisomers, are intended unless otherwise indicated. Compounds of the present invention that contain asymmetrically substituted carbon atoms can be isolated in optically active or racemic forms. Methods on how to prepare optically active forms from optically inactive starting materials are known in the art, such as by resolution of racemic mixtures or by stereoselective synthesis. Many geometric isomers of olefins, C═N double bonds and the like can also be present in the compounds described herein, and all such stable isomers are contemplated in the present invention. Cis and trans geometric isomers of the compounds of the present invention are described and may be isolated as a mixture of isomers or as separated isomeric forms.

[0420] Resolution of racemic mixtures of compounds can be carried out by any of numerous methods known in the art. One method includes fractional recrystallization using a chiral resolving acid which is an optically active, salt-forming organic acid. Suitable resolving agents for fractional recrystallization methods are, e.g., optically active acids, such as the D and L forms of tartaric acid, diacetyltartaric acid, dibenzoyltartaric acid, mandelic acid, malic acid, lactic acid or the various optically active camphorsulfonic acids such as β-camphorsulfonic acid. Other resolving agents suitable for fractional crystallization methods include stereoisomerically pure forms of α-methylbenzylamine (e.g., S and R forms, or diastereoisomerically pure forms), 2-phenylglycinol, norephedrine, ephedrine, N-methylephedrine, cyclohexylethylamine, 1,2-diaminocyclohexane and the like.

[0421] Resolution of racemic mixtures can also be carried out by elution on a column packed with an optically active resolving agent (e.g., dinitrobenzoylphenylglycine). Suitable elution solvent composition can be determined by one skilled in the art.

[0422] In some embodiments, the compounds of the invention have the (R)-configuration. In other embodiments, the compounds have the (S)-configuration. In compounds with more than one chiral centers, each of the chiral centers in the compound may be independently (R) or (S), unless otherwise indicated.

[0423] Compounds of the invention also include tautomeric forms. Tautomeric forms result from the swapping of a single bond with an adjacent double bond together with the concomitant migration of a proton. Tautomeric forms include prototropic tautomers which are isomeric protonation states having the same empirical formula and total charge. Example prototropic tautomers include ketone-enol pairs, amide-imidic acid pairs, lactam-lactim pairs, enamine-imine pairs, and annular forms where a proton can occupy two or more positions of a heterocyclic system, e.g., 1H- and 3H-imidazole, 1H-, 2H- and 4H-1,2,4-triazole, 1H- and 2H-isoindole and 1H- and 2H-pyrazole. Tautomeric forms can be in equilibrium or sterically locked into one form by appropriate substitution.

[0424] Compounds of the invention can also include all isotopes of atoms occurring in the intermediates or final compounds. Isotopes include those atoms having the same atomic number but different mass numbers. For example, isotopes of hydrogen include tritium and deuterium.

[0425] The term, “compound,” is meant to include all stereoisomers, geometric isomers, tautomers and isotopes of the structures depicted.

[0426] All compounds, and pharmaceutically acceptable salts thereof, can be found together with other substances such as water and solvents (e.g., hydrates and solvates) or can be isolated. When in the solid state, the compounds described herein and salts thereof may occur in various forms and may, e.g., take the form of solvates, including hydrates. The compounds may be in any solid state form, such as a polymorph or solvate, so unless clearly indicated otherwise, reference in the specification to compounds and salts thereof should be understood as encompassing any solid state form of the compound.

[0427] In some embodiments, the compounds of the invention, or salts thereof, are substantially isolated. By “substantially isolated” is meant that the compound is at least partially or substantially separated from the environment in which it was formed or detected. Partial separation can include, e.g., a composition enriched in the compounds of the invention. Substantial separation can include compositions containing at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, at least about 95%, at least about 97%, or at least about 99% by weight of the compounds of the invention, or salt thereof.

[0428] The phrase “pharmaceutically acceptable” is employed herein to refer to those compounds, materials, compositions and/or dosage forms which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of human beings and animals without excessive toxicity, irritation, allergic response, or other problem or complication, commensurate with a reasonable benefit/risk ratio.

[0429] The expressions, “ambient temperature” and “room temperature” are understood in the art, and refer generally to a temperature, e.g., a reaction temperature, that is about the temperature of the room in which the reaction is carried out, e.g., a temperature from about 20° C. to about 30° C.

[0430] The present invention also includes salts, particularly pharmaceutically acceptable salts, of the compounds described herein. The term “pharmaceutically acceptable salts” refers to derivatives of the disclosed compounds wherein the parent compound is modified by converting an existing acid or base moiety to its salt form. Examples of pharmaceutically acceptable salts include, but are not limited to, mineral or organic acid salts of basic residues such as amines; alkali or organic salts of acidic residues such as carboxylic acids; and the like. The pharmaceutically acceptable salts of the present invention include the non-toxic salts of the parent compound formed, e.g., from non-toxic inorganic or organic acids. The pharmaceutically acceptable salts of the present invention can be synthesized from the parent compound which contains a basic or acidic moiety by conventional chemical methods. Generally, such salts can be prepared by reacting the free acid or base forms of these compounds with a stoichiometric amount of the appropriate base or acid in water or in an organic solvent, or in a mixture of the two; generally, non-aqueous media like ether, ethyl acetate, alcohols (e.g., methanol, ethanol, iso-propanol or butanol) or acetonitrile (MeCN) are preferred. Lists of suitable salts are found in Remington's Pharmaceutical Sciences, 17.sup.th Ed., (Mack Publishing Company, Easton, 1985), p. 1418, Berge et al., J. Pharm. Sci., 1977, 66(1), 1-19 and in Stahl et al., Handbook of Pharmaceutical Salts: Properties, Selection, and Use, (Wiley, 2002). In some embodiments, the compounds described herein include the N-oxide forms.

[0431] The following abbreviations may be used herein: AcOH (acetic acid); Ac.sub.2O (acetic anhydride); Al.sub.2O.sub.3 (aluminium oxide); aq. (aqueous); atm. (atmosphere(s)); Boc (t-butoxycarbonyl); Boc.sub.2O (di-tert-butyldicarbonate); BOP ((benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate); br (broad); c-Pr (cyclopropyl); Cbz (carboxybenzyl); calc. (calculated); CeCl.sub.3.7H.sub.2O (cerium (III) chloride heptahydrate); Cs.sub.2CO.sub.3 (cesium carbonate); CuI (copper (I) iodide); d (doublet); dd (doublet of doublets); DCM (dichloromethane); DIPEA (N,N-diisopropylethylamine); DMAP (4-dimethylaminopyridine); DMF (N,N-dimethylformamide); DMSO (dimethylsulfoxide); Et (ethyl); EtOAc (ethyl acetate); EtOH (ethanol); Fmoc (9-fluorenylmethylmethoxycarbonyl); g (gram(s)); h (hour(s)); H.sub.2 (hydrogen gas); H.sub.2O.sub.2 (hydrogen peroxide); HATU (N,N,N′,N′-tetramethyl-O-(7-azabenzotriazol-1-yl)uronium hexafluorophosphate); HBr (hydrogen bromide); HCl (hydrochloric acid or hydrogen chloride); HPLC (high performance liquid chromatography); Hz (hertz); i-Pr (isopropyl); i-PrOH (isopropyl alcohol); J (coupling constant); KOAc (potassium acetate); K.sub.3PO.sub.4 (potassium phosphate); K.sub.3PO.sub.4.H.sub.2O (tripotassium phosphate hydrate); LCMS (liquid chromatography-mass spectrometry); LiAlH.sub.4 (lithium tetrahydroaluminate); LiBH.sub.4 (lithium tetrahydroborate); LiOH (lithium hydroxide); LiOH.H.sub.2O (lithium hydroxide monohydrate); m (multiplet); M (molar); mCPBA (m-chloroperbenzoic acid); Me (methyl); MeCN (acetonitrile); MeOH (methanol); MgSO.sub.4 (magnesium sulfate); MS (mass spectrometry); mg (milligram(s)); min. (minutes(s)); mL (milliliter(s)); mmol (millimole(s)); N (normal); N.sub.2 (nitrogen gas); NaHCO.sub.3 (sodium bicarbonate); NaIO.sub.4 (sodium metaperiodate); NaN.sub.3 (sodium azide); NaOH (sodium hydroxide); Na.sub.2SO.sub.4 (sodium sulfate); n-Bu (n-butyl); n-BuLi (n-butyllithium); NH.sub.4Cl (ammonium chloride); NH.sub.4OH (ammonium hydroxide); nM (nanomolar); NMR (nuclear magnetic resonance spectroscopy); Pd (palladium); Pd(dppf)Cl.sub.2 ([1,1′-bis(diphenylphosphino)ferrocene]palladium(II) dichloride); Pd(OAc).sub.2 (palladium acetate); Pd(tBu.sub.3P).sub.2 (bis(tri-tert-butylphosphine)palladium); pM (picomolar); Pd(PPh.sub.3).sub.4 (tetrakis(triphenylphosphine)palladium(O)); PPh.sub.3 (triphenylphosphine); psi (pounds per square inch); PTFE (polytetrafluoroethylene); RP-HPLC (reverse phase high performance liquid chromatography); r.t. (room temperature); s (singlet); t (triplet or tertiary); tert (tertiary); tt (triplet of triplets); TBAF (tetra-n-butylammoniumfluoride); t-Bu (tert-butyl); TEA (triethylamine); TFA (trifluoroacetic acid); THF (tetrahydrofuran); μg (microgram(s)); μL (microliter(s)); m (micromolar); wt % (weight percent).

II. SYNTHESIS

[0432] Compounds of the invention, including salts thereof, can be prepared using known organic synthesis techniques and can be synthesized according to any of numerous possible synthetic routes, such as shown in the Scheme below.

[0433] The reactions for preparing compounds of the invention can be carried out in suitable solvents which can be readily selected by one of skill in the art of organic synthesis. Suitable solvents can be substantially non-reactive with the starting materials (reactants), the intermediates or products at the temperatures at which the reactions are carried out, e.g., temperatures which can range from the solvent's freezing temperature to the solvent's boiling temperature. A given reaction can be carried out in one solvent or a mixture of more than one solvent. Depending on the particular reaction step, suitable solvents for a particular reaction step can be selected by the skilled artisan.

[0434] Preparation of compounds of the invention can involve the protection and deprotection of various chemical groups. The need for protection and deprotection, and the selection of appropriate protecting groups, can be readily determined by one skilled in the art. The chemistry of protecting groups is described, e.g., in Kocienski, Protecting Groups, (Thieme, 2007); Robertson, Protecting Group Chemistry, (Oxford University Press, 2000); Smith et al., March's Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, 6.sup.th Ed. (Wiley, 2007); Peturssion et al., “Protecting Groups in Carbohydrate Chemistry,” J. Chem. Educ., 1997, 74(11), 1297; and Wuts et al., Protective Groups in Organic Synthesis, 4th Ed., (Wiley, 2006).

[0435] Reactions can be monitored according to any suitable method known in the art. For example, product formation can be monitored by spectroscopic means, such as nuclear magnetic resonance spectroscopy (e.g., .sup.1H or .sup.13C), infrared spectroscopy, spectrophotometry (e.g., UV-visible), mass spectrometry or by chromatographic methods such as high performance liquid chromatography (HPLC) or thin layer chromatography (TLC).

[0436] The Schemes below provide general guidance in connection with preparing the compounds of the invention. One skilled in the art would understand that the preparations shown in the Schemes can be modified or optimized using general knowledge of organic chemistry to prepare various compounds of the invention.

[0437] Compounds of Formula (I) can be prepared as shown in Scheme 1 by coupling an aniline of Formula (II) with a compound of formula III, wherein L is a suitable leaving group, which can include halogen, such as bromine or iodine, or a sulfonate group (alkyl or aryl sulfonate, such as methanesulfonate, trifluoromethanesulfonate, benzenesulfonate, p-toluenesulfonate, or naphthalenesulfonate). The reaction can be carried out in the presence of a base such as potassium carbonate and a copper salt such as copper (I) iodide or copper (I) oxide. The reaction can also be carried out in the presence of a suitable organometallic catalyst, e.g., using Buchwald-Hartwig cross-coupling conditions. Suitable solvents for the reaction include tetrahydrofuran, 1,4-dioxane, tolune, or 1,2-dichlorobenzene. The preferred solvent is 1,2-dichlorobenzene. The reaction can typically be performed at a temperature of 0-200° C., e.g., a temperature of 100-150° C.

[0438] The present disclosure provides, inter alia, a methods of making certain compounds of Formula (I) according to Formula (Ia) by the route shown in Scheme 1:

##STR00092##

[0439] Compounds of Formula (II) and (III) are either commercially available, known in the literature, or may be prepared by methods known to one skilled in the art.

[0440] Certain compounds of formula (I) may be useful as intermediates in the synthesis of other compounds of formula (I). For example, compounds of formula (I) wherein R.sup.1 is OC.sub.1-6 alkyl, OCy.sup.1A, O(C.sub.1-3 alkylenyl)Cy.sup.1A, NHCy.sup.1A NH(C.sub.1-3 alkylenyl)Cy.sup.1A, N(C.sub.1-6 alkyl)Cy.sup.1A, or N(C.sub.1-6 alkyl)(C.sub.1-3 alkylenyl)Cy.sup.1A can be used to synthesize compounds of formula (I) wherein R.sup.1 is OH via hydrolysis of the ester or amide group.

[0441] It will be appreciated by one skilled in the art that the processes described are not the exclusive means by which compounds of the invention may be synthesized and that a broad repertoire of synthetic organic reactions is available to be potentially employed in synthesizing compounds of the invention. The person skilled in the art knows how to select and implement appropriate synthetic routes. Suitable synthetic methods of starting materials, intermediates and products may be identified by reference to the literature, including reference sources such as: Advances in Heterocyclic Chemistry, Vols. 1-107 (Elsevier, 1963-2012); Journal of Heterocyclic Chemistry Vols. 1-49 (Journal of Heterocyclic Chemistry, 1964-2012); Carreira, et al. (Ed.) Science of Synthesis, Vols. 1-48 (2001-2010) and Knowledge Updates KU2010/1-4; 2011/1-4; 2012/1-2 (Thieme, 2001-2012); Katritzky, et al. (Ed.) Comprehensive Organic Functional Group Transformations, (Pergamon Press, 1996); Katritzky et al. (Ed.); Comprehensive Organic Functional Group Transformations II (Elsevier, 2.sup.nd Edition, 2004); Katritzky et al. (Ed.), Comprehensive Heterocyclic Chemistry (Pergamon Press, 1984); Katritzky et al., Comprehensive Heterocyclic Chemistry II, (Pergamon Press, 1996); Smith et al., March's Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, 6.sup.th Ed. (Wiley, 2007); Trost et al. (Ed.), Comprehensive Organic Synthesis (Pergamon Press, 1991).

III. USES OF THE COMPOUNDS

[0442] Compounds of the invention can inhibit the autopalmitoylation of TEAD-transcription factors and, thus, are useful in treating diseases and disorders associated with activity of TEAD-transcription factors. For the uses described herein, any of the compounds of the invention, including any of the embodiments thereof, may be used.

[0443] Thus, the present disclosure provides methods of treating a TEAD-transcription factor-associated disease or disorder in an individual (e.g., patient) by administering to the individual in need of such treatment a therapeutically effective amount or dose of a compound of Formula (I), or any of the embodiments thereof, or a pharmaceutical composition thereof. The present disclosure also provides a compound of Formula (I), or any of the embodiments thereof, or a pharmaceutical composition thereof, for use in treating a TEAD-transcription factor associated disease or disorder. Also provided is the use of a compound of Formula (I), or any of the embodiments thereof, or a pharmaceutical composition thereof, in the manufacture of a medicament for treating a TEAD-transcription factor-associated disease or disorder. The disease or disorder can be one that is associated with TEAD1, TEAD2, TEAD3, or TEAD4.

[0444] A TEAD-transcription factor-associated disease can include any disease, disorder or condition that is directly or indirectly linked to expression or activity of TEAD-transcription factors, including over-expression and/or abnormal activity levels. Abnormal activity levels can be determined by comparing activity level in normal, healthy tissue or cells with activity level in diseased cells. A TEAD-transcription factor-associated disease can also include any disease, disorder or condition that can be prevented, ameliorated, inhibited or cured by modulating TEAD-transcription factor activity. In some embodiments, the disease is characterized by the abnormal activity or expression (e.g., overexpression) of TEAD-transcription factor. A TEAD-transcription factor-associated disease can also refer to any disease, disorder or condition wherein modulating the expression or activity TEAD-transcription factor is beneficial.

[0445] TEAD-transcription factor associated diseases that can be treated using the compounds of the invention include cancer. The cancers include solid tumors, e.g., prostate cancer, colon cancer, esophageal cancer, endometrial cancer, ovarian cancer, uterine cancer, renal cancer, hepatic cancer, pancreatic cancer, gastric cancer, breast cancer, lung cancer, cancers of the head or neck, thyroid cancer, glioblastoma, sarcoma, bladder cancer, etc. Other TEAD-transcription factor associated diseases include hepatocellular carcinoma, medulloblastoma, cutaneous squamous cell carcinoma, lung cancer, pancreatic cancer, esophagus cancer, liver cancer, colon cancer, melanoma, or uveal melanoma. TEAD-transcription factor associated diseases also include hematological cancers, e.g., lymphoma, leukemia such as acute lymphoblastic leukemia (ALL), acute myelogenous leukemia (AML), chronic lymphocytic leukemia (CLL), chronic myelogenous leukemia (CML), diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma, non-Hodgkin lymphoma (including relapsed non-Hodgkin lymphoma, refractory non-Hodgkin lymphoma and recurrent follicular non-Hodgkin lymphoma), Hodgkin lymphoma and multiple myeloma.

[0446] The cancer can be a cancer in which abnormally proliferating cells of the cancer express one or more TEADs, for example, a cancer that expresses one or more of TEAD1, TEAD2, TEAD3, and/or TEAD4. The method can include testing cancer cells of the individual for expression of one or more TEADs, e.g., one or more of TEAD1, TEAD2, TEAD3, and/or TEAD4, and treating the cancer according to the methods described herein based on the determination that the cancer expresses TEAD1, TEAD2, TEAD3, and/or TEAD4.

[0447] The terms “individual” or “patient,” used interchangeably, refer to any animal, including mammals, preferably mice, rats, other rodents, rabbits, dogs, cats, swine, cattle, sheep, horses, or primates, and most preferably humans.

[0448] The phrase “therapeutically effective amount” refers to the amount of active compound or pharmaceutical agent that elicits the biological or medicinal response in a tissue, system, animal, individual or human that is being sought by a researcher, veterinarian, medical doctor or other clinician.

[0449] The term “treating” or “treatment” refers to one or more of (1) inhibiting the disease; e.g., inhibiting a disease, condition or disorder in an individual who is experiencing or displaying the pathology or symptomatology of the disease, condition or disorder (i.e., arresting further development of the pathology and/or symptomatology); and (2) ameliorating the disease; e.g., ameliorating a disease, condition or disorder in an individual who is experiencing or displaying the pathology or symptomatology of the disease, condition or disorder (i.e., reversing the pathology and/or symptomatology) such as decreasing the severity of disease. In one embodiment, treating or treatment includes preventing or reducing the risk of developing the disease; e.g., preventing or reducing the risk of developing a disease, condition or disorder in an individual who may be predisposed to the disease, condition or disorder but does not yet experience or display the pathology or symptomatology of the disease.

Combination Therapies

[0450] Cancer cell growth and survival can be impacted by multiple signaling pathways. Thus, it is useful to combine different chemotherapeutic agents treat such conditions. Use of combination therapy may reduce the likelihood of drug-resistance arising in a cell population, and/or reduce the toxicity of treatment.

[0451] The compounds can be administered in combination with one or more anti-cancer drugs, such as a chemotherapeutics. Example chemotherapeutics include any of: abarelix, aldesleukin, alemtuzumab, alitretinoin, allopurinol, altretamine, anastrozole, arsenic trioxide, asparaginase, azacitidine, bevacizumab, bexarotene, bleomycin, bortezombi, bortezomib, busulfan intravenous, busulfan oral, calusterone, capecitabine, carboplatin, carmustine, cetuximab, chlorambucil, cisplatin, cladribine, clofarabine, cyclophosphamide, cytarabine, dacarbazine, dactinomycin, dalteparin sodium, dasatinib, daunorubicin, decitabine, denileukin, denileukin diftitox, dexrazoxane, docetaxel, doxorubicin, dromostanolone propionate, eculizumab, epirubicin, erlotinib, estramustine, etoposide phosphate, etoposide, exemestane, fentanyl citrate, filgrastim, floxuridine, fludarabine, fluorouracil, fulvestrant, gefitinib, gemcitabine, gemtuzumab ozogamicin, goserelin acetate, histrelin acetate, ibritumomab tiuxetan, idarubicin, ifosfamide, imatinib mesylate, interferon alfa 2a, irinotecan, lapatinib ditosylate, lenalidomide, letrozole, leucovorin, leuprolide acetate, levamisole, lomustine, meclorethamine, megestrol acetate, melphalan, mercaptopurine, methotrexate, methoxsalen, mitomycin C, mitotane, mitoxantrone, nandrolone phenpropionate, nelarabine, nofetumomab, oxaliplatin, paclitaxel, pamidronate, panitumumab, pegaspargase, pegfilgrastim, pemetrexed disodium, pentostatin, pipobroman, plicamycin, procarbazine, quinacrine, rasburicase, rituximab, ruxolitinib, sorafenib, streptozocin, sunitinib, sunitinib maleate, tamoxifen, temozolomide, teniposide, testolactone, thalidomide, thioguanine, thiotepa, topotecan, toremifene, tositumomab, trastuzumab, tretinoin, uracil mustard, valrubicin, vinblastine, vincristine, vinorelbine, vorinostat and zoledronate.

[0452] When more than one pharmaceutical agent is administered to a patient, they can be administered simultaneously, sequentially, or in combination (e.g., for more than two agents).

VI. Formulation, Dosage Forms and Administration

[0453] When employed as pharmaceuticals, the compounds of the invention can be administered in the form of pharmaceutical compositions. Thus the present disclosure provides a composition comprising a compound Formula (I), or a pharmaceutically acceptable salt thereof, or any of the embodiments thereof, and at least one pharmaceutically acceptable carrier. These compositions can be prepared in a manner well known in the pharmaceutical art, and can be administered by a variety of routes, depending upon whether local or systemic treatment is indicated and upon the area to be treated. Administration may be topical (including transdermal, epidermal, ophthalmic and to mucous membranes including intranasal, vaginal and rectal delivery), pulmonary (e.g., by inhalation or insufflation of powders or aerosols, including by nebulizer; intratracheal or intranasal), oral or parenteral. Parenteral administration includes intravenous, intraarterial, subcutaneous, intraperitoneal intramuscular or injection or infusion; or intracranial, e.g., intrathecal or intraventricular, administration. Parenteral administration can be in the form of a single bolus dose, or may be, e.g., by a continuous perfusion pump. Pharmaceutical compositions and formulations for topical administration may include transdermal patches, ointments, lotions, creams, gels, drops, suppositories, sprays, liquids and powders. Conventional pharmaceutical carriers, aqueous, powder or oily bases, thickeners and the like may be necessary or desirable.

[0454] This invention also includes pharmaceutical compositions which contain, as the active ingredient, the compound of the invention or a pharmaceutically acceptable salt thereof, in combination with one or more pharmaceutically acceptable carriers (excipients). In some embodiments, the composition is suitable for topical administration. In making the compositions of the invention, the active ingredient is typically mixed with an excipient, diluted by an excipient or enclosed within such a carrier in the form of, e.g., a capsule, sachet, paper, or other container. When the excipient serves as a diluent, it can be a solid, semi-solid, or liquid material, which acts as a vehicle, carrier or medium for the active ingredient. Thus, the compositions can be in the form of tablets, pills, powders, lozenges, sachets, cachets, elixirs, suspensions, emulsions, solutions, syrups, aerosols (as a solid or in a liquid medium), ointments containing, e.g., up to 10% by weight of the active compound, soft and hard gelatin capsules, suppositories, sterile injectable solutions and sterile packaged powders.

[0455] In preparing a formulation, the active compound can be milled to provide the appropriate particle size prior to combining with the other ingredients. If the active compound is substantially insoluble, it can be milled to a particle size of less than 200 mesh. If the active compound is substantially water soluble, the particle size can be adjusted by milling to provide a substantially uniform distribution in the formulation, e.g., about 40 mesh.

[0456] The compounds of the invention may be milled using known milling procedures such as wet milling to obtain a particle size appropriate for tablet formation and for other formulation types. Finely divided (nanoparticulate) preparations of the compounds of the invention can be prepared by processes known in the art see, e.g., WO 2002/000196.

[0457] Some examples of suitable excipients include lactose, dextrose, sucrose, sorbitol, mannitol, starches, gum acacia, calcium phosphate, alginates, tragacanth, gelatin, calcium silicate, microcrystalline cellulose, polyvinylpyrrolidone, cellulose, water, syrup and methyl cellulose. The formulations can additionally include: lubricating agents such as talc, magnesium stearate and mineral oil; wetting agents; emulsifying and suspending agents; preserving agents such as methyl- and propylhydroxy-benzoates; sweetening agents; and flavoring agents. The compositions of the invention can be formulated so as to provide quick, sustained or delayed release of the active ingredient after administration to the patient by employing procedures known in the art.

[0458] In some embodiments, the pharmaceutical composition comprises silicified microcrystalline cellulose (SMCC) and at least one compound described herein, or a pharmaceutically acceptable salt thereof. In some embodiments, the silicified microcrystalline cellulose comprises about 98% microcrystalline cellulose and about 2% silicon dioxide w/w.

[0459] In some embodiments, the composition is a sustained release composition comprising at least one compound described herein, or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier. In some embodiments, the composition comprises at least one compound described herein, or a pharmaceutically acceptable salt thereof, and at least one component selected from microcrystalline cellulose, lactose monohydrate, hydroxypropyl methylcellulose and polyethylene oxide. In some embodiments, the composition comprises at least one compound described herein, or a pharmaceutically acceptable salt thereof, and microcrystalline cellulose, lactose monohydrate and hydroxypropyl methylcellulose. In some embodiments, the composition comprises at least one compound described herein, or a pharmaceutically acceptable salt thereof, and microcrystalline cellulose, lactose monohydrate and polyethylene oxide. In some embodiments, the composition further comprises magnesium stearate or silicon dioxide. In some embodiments, the microcrystalline cellulose is Avicel PH102™. In some embodiments, the lactose monohydrate is Fast-flo 316™. In some embodiments, the hydroxypropyl methylcellulose is hydroxypropyl methylcellulose 2208 K4M (e.g., Methocel K4 M Premier™) and/or hydroxypropyl methylcellulose 2208 K100LV (e.g., Methocel KOOLV™). In some embodiments, the polyethylene oxide is polyethylene oxide WSR 1105 (e.g., Polyox WSR 1105™).

[0460] In some embodiments, a wet granulation process is used to produce the composition. In some embodiments, a dry granulation process is used to produce the composition.

[0461] The compositions can be formulated in a unit dosage form, each dosage containing from about 5 to about 1,000 mg (1 g), more usually about 100 mg to about 500 mg, of the active ingredient. In some embodiments, each dosage contains about 10 mg of the active ingredient. In some embodiments, each dosage contains about 50 mg of the active ingredient. In some embodiments, each dosage contains about 25 mg of the active ingredient. The term “unit dosage forms” refers to physically discrete units suitable as unitary dosages for human subjects and other mammals, each unit containing a predetermined quantity of active material calculated to produce the desired therapeutic effect, in association with a suitable pharmaceutical excipient.

[0462] The components used to formulate the pharmaceutical compositions are of high purity and are substantially free of potentially harmful contaminants (e.g., at least National Food grade, generally at least analytical grade, and more typically at least pharmaceutical grade). Particularly for human consumption, the composition is preferably manufactured or formulated under Good Manufacturing Practice standards as defined in the applicable regulations of the U.S. Food and Drug Administration. For example, suitable formulations may be sterile and/or substantially isotonic and/or in full compliance with all Good Manufacturing Practice regulations of the U.S. Food and Drug Administration.

[0463] The active compound may be effective over a wide dosage range and is generally administered in a therapeutically effective amount. It will be understood, however, that the amount of the compound actually administered will usually be determined by a physician, according to the relevant circumstances, including the condition to be treated, the chosen route of administration, the actual compound administered, the age, weight, and response of the individual patient, the severity of the patient's symptoms and the like.

[0464] The therapeutic dosage of a compound of the present invention can vary according to, e.g., the particular use for which the treatment is made, the manner of administration of the compound, the health and condition of the patient, and the judgment of the prescribing physician. The proportion or concentration of a compound of the invention in a pharmaceutical composition can vary depending upon a number of factors including dosage, chemical characteristics (e.g., hydrophobicity), and the route of administration. For example, the compounds of the invention can be provided in an aqueous physiological buffer solution containing about 0.1 to about 10% w/v of the compound for parenteral administration. Some typical dose ranges are from about 1 μg/kg to about 1 g/kg of body weight per day. In some embodiments, the dose range is from about 0.01 mg/kg to about 100 mg/kg of body weight per day. The dosage is likely to depend on such variables as the type and extent of progression of the disease or disorder, the overall health status of the particular patient, the relative biological efficacy of the compound selected, formulation of the excipient, and its route of administration. Effective doses can be extrapolated from dose-response curves derived from in vitro or animal model test systems.

[0465] For preparing solid compositions such as tablets, the principal active ingredient is mixed with a pharmaceutical excipient to form a solid preformulation composition containing a homogeneous mixture of a compound of the present invention. When referring to these preformulation compositions as homogeneous, the active ingredient is typically dispersed evenly throughout the composition so that the composition can be readily subdivided into equally effective unit dosage forms such as tablets, pills and capsules. This solid preformulation is then subdivided into unit dosage forms of the type described above containing from, e.g., about 0.1 to about 1000 mg of the active ingredient of the present invention.

[0466] The tablets or pills of the present invention can be coated or otherwise compounded to provide a dosage form affording the advantage of prolonged action. For example, the tablet or pill can comprise an inner dosage and an outer dosage component, the latter being in the form of an envelope over the former. The two components can be separated by an enteric layer which serves to resist disintegration in the stomach and permit the inner component to pass intact into the duodenum or to be delayed in release. A variety of materials can be used for such enteric layers or coatings, such materials including a number of polymeric acids and mixtures of polymeric acids with such materials as shellac, cetyl alcohol and cellulose acetate.

[0467] The liquid forms in which the compounds and compositions of the present invention can be incorporated for administration orally or by injection include aqueous solutions, suitably flavored syrups, aqueous or oil suspensions, and flavored emulsions with edible oils such as cottonseed oil, sesame oil, coconut oil, or peanut oil, as well as elixirs and similar pharmaceutical vehicles.

[0468] Compositions for inhalation or insufflation include solutions and suspensions in pharmaceutically acceptable, aqueous or organic solvents, or mixtures thereof, and powders. The liquid or solid compositions may contain suitable pharmaceutically acceptable excipients as described supra. In some embodiments, the compositions are administered by the oral or nasal respiratory route for local or systemic effect. Compositions can be nebulized by use of inert gases. Nebulized solutions may be breathed directly from the nebulizing device or the nebulizing device can be attached to a face mask, tent, or intermittent positive pressure breathing machine. Solution, suspension, or powder compositions can be administered orally or nasally from devices which deliver the formulation in an appropriate manner.

[0469] Topical formulations can contain one or more conventional carriers. In some embodiments, ointments can contain water and one or more hydrophobic carriers selected from, e.g., liquid paraffin, polyoxyethylene alkyl ether, propylene glycol, white Vaseline, and the like. Carrier compositions of creams can be based on water in combination with glycerol and one or more other components, e.g., glycerinemonostearate, PEG-glycerinemonostearate and cetylstearyl alcohol. Gels can be formulated using isopropyl alcohol and water, suitably in combination with other components such as, e.g., glycerol, hydroxyethyl cellulose, and the like. In some embodiments, topical formulations contain at least about 0.1, at least about 0.25, at least about 0.5, at least about 1, at least about 2 or at least about 5 wt % of the compound of the invention. The topical formulations can be suitably packaged in tubes of, e.g., 100 g which are optionally associated with instructions for the treatment of the select indication, e.g., psoriasis or other skin condition.

[0470] The amount of compound or composition administered to a patient will vary depending upon what is being administered, the purpose of the administration, such as prophylaxis or therapy, the state of the patient, the manner of administration and the like. In therapeutic applications, compositions can be administered to a patient already suffering from a disease in an amount sufficient to cure or at least partially arrest the symptoms of the disease and its complications. Effective doses will depend on the disease condition being treated as well as by the judgment of the attending clinician depending upon factors such as the severity of the disease, the age, weight and general condition of the patient and the like.

[0471] The compositions administered to a patient can be in the form of pharmaceutical compositions described above. These compositions can be sterilized by conventional sterilization techniques, or may be sterile filtered. Aqueous solutions can be packaged for use as is, or lyophilized, the lyophilized preparation being combined with a sterile aqueous carrier prior to administration. The pH of the compound preparations typically will be between 3 and 11, more preferably from 5 to 9 and most preferably from 7 to 8. It will be understood that use of certain of the foregoing excipients, carriers or stabilizers will result in the formation of pharmaceutical salts.

[0472] The therapeutic dosage of a compound of the present invention can vary according to, e.g., the particular use for which the treatment is made, the manner of administration of the compound, the health and condition of the patient, and the judgment of the prescribing physician. The proportion or concentration of a compound of the invention in a pharmaceutical composition can vary depending upon a number of factors including dosage, chemical characteristics (e.g., hydrophobicity), and the route of administration. For example, the compounds of the invention can be provided in an aqueous physiological buffer solution containing about 0.1 to about 10% w/v of the compound for parenteral administration. Some typical dose ranges are from about 1 μg/kg to about 1 g/kg of body weight per day. In some embodiments, the dose range is from about 0.01 mg/kg to about 100 mg/kg of body weight per day. The dosage is likely to depend on such variables as the type and extent of progression of the disease or disorder, the overall health status of the particular patient, the relative biological efficacy of the compound selected, formulation of the excipient, and its route of administration. Effective doses can be extrapolated from dose-response curves derived from in vitro or animal model test systems.

IV. Labeled Compounds and Assay Methods

[0473] The compounds of the invention can further be useful in investigations of biological processes in normal and abnormal tissues. Thus, another aspect of the present invention relates to labeled compounds of the invention (radio-labeled, fluorescent-labeled, etc.) that would be useful not only in imaging techniques but also in assays, both in vitro and in vivo, for localizing and quantitating TEAD transcription factor in tissue samples, including human, and for identifying TEAD transcription factor ligands by inhibition binding of a labeled compound. Accordingly, the present invention includes assays that contain such labeled compounds.

[0474] The present invention further includes isotopically-labeled compounds of the invention. An “isotopically” or “radio-labeled” compound is a compound of the invention where one or more atoms are replaced or substituted by an atom having an atomic mass or mass number different from the atomic mass or mass number typically found in nature (i.e., naturally occurring). Suitable radionuclides that may be incorporated in compounds of the present invention include but are not limited to .sup.3H (also written as T for tritium), .sup.11C, .sup.13C, .sup.14C, .sup.13N, .sup.15N, .sup.15O, .sup.17O, .sup.18O, .sup.18F, .sup.35S, .sup.36Cl, .sup.82Br, .sup.75Br, .sup.76Br, .sup.77Br, .sup.123I, .sup.124I, .sup.125I and .sup.131I. The radionuclide that is incorporated in the instant radio-labeled compounds will depend on the specific application of that radio-labeled compound. For example, for in vitro labeling and competition assays, compounds that incorporate .sup.3H, .sup.14C, .sup.82Br, .sup.125I, .sup.131I, .sup.35S or will generally be most useful. For radio-imaging applications .sup.11C, .sup.18F, .sup.125I, .sup.123I, .sup.124I, .sup.131I, .sup.75Br, .sup.76Br or .sup.77Br will generally be most useful.

[0475] It is to be understood that a “radio-labeled” or “labeled compound” is a compound that has incorporated at least one radionuclide. In some embodiments the radionuclide is selected from the group consisting of .sup.3H, .sup.14C, .sup.125I, .sup.35S and .sup.82Br. In some embodiments, the compound incorporates 1, 2 or 3 deuterium atoms. Synthetic methods for incorporating radio-isotopes into organic compounds are known in the art.

[0476] Specifically, a labeled compound of the invention can be used in a screening assay to identify and/or evaluate compounds. For example, a newly synthesized or identified compound (i.e., test compound) which is labeled can be evaluated for its ability to bind a TEAD transcription factor by monitoring its concentration variation when contacting with the TEAD transcription factor, through tracking of the labeling. For example, a test compound (labeled) can be evaluated for its ability to reduce binding of another compound which is known to bind to a TEAD transcription factor (i.e., standard compound). Accordingly, the ability of a test compound to compete with the standard compound for binding to the TEAD transcription factor directly correlates to its binding affinity. Conversely, in some other screening assays, the standard compound is labeled and test compounds are unlabeled. Accordingly, the concentration of the labeled standard compound is monitored in order to evaluate the competition between the standard compound and the test compound, and the relative binding affinity of the test compound is thus ascertained.

V. Kits

[0477] The present disclosure also includes pharmaceutical kits useful, e.g., in the treatment or prevention of TEAD transcription factor-associated diseases or disorders, such as cancer, which include one or more containers containing a pharmaceutical composition comprising a therapeutically effective amount of a compound of Formula (I), or any of the embodiments thereof. Such kits can further include one or more of various conventional pharmaceutical kit components, such as, e.g., containers with one or more pharmaceutically acceptable carriers, additional containers, etc., as will be readily apparent to those skilled in the art. Instructions, either as inserts or as labels, indicating quantities of the components to be administered, guidelines for administration, and/or guidelines for mixing the components, can also be included in the kit.

[0478] The invention will be described in greater detail by way of specific examples. The following examples are offered for illustrative purposes, and are not intended to limit the invention in any manner. Those of skill in the art will readily recognize a variety of non-critical parameters which can be changed or modified to yield essentially the same results.

EXAMPLES

Compound Synthesis

[0479] Experimental:

[0480] The MS (Mass Spectral) data provided in the examples were obtained using the following equipment: API 2000 LC/MS/MS/Triple quad; Agilent (1260 infinity) LCMS-SQD 6120/Single quad and Shimadzu LCMS-2020/Single quad.

[0481] The NMR data provided in the examples were obtained using the equipment-.sup.1HNMR: .sup.1HNMR: Varian −400 MHz, JEOL −400 MHz.

[0482] The abbreviations used in the entire specification may be summarized herein below with their particular meaning.

[0483] ° C. (degree Celsius); δ (delta); % (percentage); (BOC).sub.2O (Boc anhydride); bs (Broad singlet); CDCl.sub.3 (Deuterated chloroform); DCM (Dichloromethane); DMF (Dimethyl formamide); DIPEA (N, N-Diisopropyl ethylamine); DMAP (Dimethyl aminopyridine); (DMSO-d6 (Deuterated DMSO); d (Doublet); dd (Doublet of doublet); Fe (Iron powder); g or gm (gram); HATU (1-[bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium 3-oxid hexafluorophosphate); H or H.sub.2 (Hydrogen); H.sub.2O (Water); HCl (Hydrochloric acid); h or hr (Hours); Hz (Hertz); HPLC (High-performance liquid chromatography); J (Coupling constant); LiOH (Lithium hydroxide); MeOH (Methanol); mmol (Millimol); M (Molar); mL (Millilitre); mg (Milligram); m (Multiplet); mm (Millimeter); MHz (Megahertz); min (Minutes); NaH (Sodium hydride); NaHCO.sub.3 (Sodium bicarbonate); Na.sub.2SO.sub.4 (Sodium sulphate); N.sub.2 (Nitrogen); NMR (Nuclear magnetic resonance spectroscopy); Pd/C (palladium carbon); RT (Room Temperature); s (Singlet); TEA (Triethylamine); TFA (Trifluoroacetic acid); TLC (Thin Layer Chromatography); THE (Tetrahydrofuran); t (Triplet); rac.BINAP ((±)-2,2′-Bis(diphenylphosphino)-1,1′-binaphthalene); Pd.sub.2dba.sub.3 (Tris(dibenzylideneacetone) dipalladium(0)); XPhos (2-Dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl); in vacuo (under vacuum); eq. (equivalents); ppt (precipitate); NA (not available).

[0484] A general procedure for the synthesis of certain exemplified compounds is shown in Scheme II below:

##STR00093##

[0485] To a solution of iodide (1 mmol) and amine (1 mmol) in 1,2-dichlorobenzene was added potassium carbonate (1.5 mmol) under nitrogen atmosphere followed by copper iodide (0.05 mmol). Resulting mixture was stirred at r.t. for 1 h and then heated at 180° C. for 2 days. After completion of the reaction resulting mixture was diluted with dichloromethane (50 mL) and filtered through bed of diatomaceous earth. The organic solution was dried with MgSO.sub.4, concentrated in vacuo and purified by flash column chromatography with hexane/ethyl acetate (gradient of pure hexane to 20/1 hexane/ethyl acetate) as eluent Yield 40-69%.

[0486] Compound 2a was confirmed with proton NMR and Mass spectroscopy (ESI) and (R.sub.f of 0.3 with pure hexane as eluent TLC).

[0487] For Compound 2a .sup.1H NMR (500 MHz, CDCl.sub.3): δ 9.46 (s, 1H), 7.98-7.94 (m, 1H), 7.40 (s, 1H), 7.35 (m, 1H), 7.28 (d, 1H), 7.19-7.13 (m, 3H), 6.79 (m, 1H), 3.90 (s, 3H) ppm. Mass (M+H, 307.1) Yield 56%.

[0488] Compound 2b (M+H 306.1), 2c (M+H 375.1), 2d (M+H 325.1), 2e (M+H 443.1) were confirmed with Mass spectroscopy (LC-MS/ESI) and also consistent on TLC with retention factor (R.sub.f of 0.3 with pure hexane as eluent).

[0489] A general procedure for synthesis of starting material for compounds CP-59 and CP-65 is shown in Scheme 3 below:

##STR00094##

[0490] The requisite amine (1 mmol) and chloro-nicotinate (1 mmol) were dissolved in ethylene glycol and then heated at 140° C. for 24 h. After completion of the reaction resulting mixture was diluted with ethyl acetate (50 mL) and washed three times with 20 mL of water. The organic solution was dried with MgSO.sub.4, concentrated in vacuo and purified by flash column chromatography with hexane/ethyl acetate (gradient of pure hexane to 15/1 hexane/ethyl acetate) as eluent. Yield 55-59%

[0491] Compound 2f (M+H, 376.1) and 2g (M+H, 322.1) were confirmed with spectroscopy (ESI) and (R.sub.f of 0.1 with pure hexane as eluent TLC)

[0492] A cross-coupling procedure used in the preparation of several example compounds is shown in Scheme 4 below.

##STR00095##

[0493] To an oven-dried Schlenk tube was added amine (1 mmol) and bromide (1 mmol) and toluene (3 mL). To the above homogeneous solution t-BuONa (1.5 mmol) was added. After stirring for 5 minutes, Pd.sub.2(dba).sub.3 (0.05 mmol) and Bu.sub.3P (0.075 mmol), were added under nitrogen atmosphere. The mixture was stirred for 24 h at 110° C. After cooling to r.t., the reaction mixture was diluted with ethyl acetate (50 mL) and filtered through bed of diatomaceous earth. The organic solution was dried with MgSO.sub.4, concentrated in vacuo and purified by flash column chromatography with hexane/ethyl acetate (gradient of pure hexane to 10/1 hexane/ethyl acetate) as eluent to give desired product. Yield 42-55%

[0494] For Compound 3a .sup.1H NMR (500 MHz, CDCl.sub.3): δ 9.45 (s, 1H), 8.01 (s, 1H), 7.5-7.7.30 (m, 2H), 7.2-7.1 (m, 2H), 6.98 (s, 1H), 6.8 (s, 1H) 6.78-6.26 (m, 4H), 5.99 (s, 1H) 3.90 (s, 3H), 2.23-1.97 (m, 15H) ppm

[0495] For Compound 3c .sup.1H NMR (500 MHz, CDCl.sub.3): δ 9.45 (s, 1H), 8.01 (s, 1H), 7.45-7.23. (d, 2H), 7.23-7.01 (m, 6H), 6.98-7.01 (d, 2H), 6.94 (s, 1H), 3.93 (s, 3H), 5.99 (s, 1H) 2.21-1.98 (m, 15H) ppm

[0496] For Compound 3d .sup.1H NMR (500 MHz, CDCl.sub.3): δ 9.45 (s, 1H), 8.01 (s, 1H), 7.45-7.01 (m, 4H), 6.94 (s, 1H), 6.63 (s, 1H) 6.65-6.20 (m, 4H), 5.98 (s, 1H) 3.92 (s, 3H), 2.21-1.98 (m, 15H) ppm

[0497] A cross-coupling procedure used in the preparation of several example compounds is shown in Scheme 5 below.

##STR00096##

[0498] To an oven-dried Schlenk tube was added amine (1 mmol) and bromide (1 mmol) and toluene (3 mL). To the above homogeneous solution t-BuONa (1.5 mmol) was added. After stirring for 5 minutes, Pd.sub.2(dba).sub.3 (0.05 mmol) and Bu.sub.3P (0.075 mmol), were added under nitrogen atmosphere. The mixture was stirred for 24 h at 110° C. After cooling to r.t., the reaction mixture was diluted with ethyl acetate (50 mL) and filtered through bed of diatomaceous earth. The organic solution was dried with MgSO.sub.4, concentrated in vacuo and purified by flash column chromatography with hexane/ethyl acetate (gradient of pure hexane to 10/1 hexane/ethyl acetate) as eluent to give desired product. Yield 50-54%

[0499] For Compound 3f .sup.1H NMR (500 MHz, CDCl.sub.3): δ 9.45 (s, 1H), 8.01 (s, 1H), 7.49-7.33. (d, 2H), 7.23-7.01 (m, 5H), 6.91-7.04 (d, 2H), 6.94 (s, 1H), 3.93 (s, 3H), 5.99 (s, 1H) 2.21-1.98 (m, 15H) ppm

[0500] Compound 3g confirmed with LC-MS/ESI (M+H 468.57)

[0501] A cross-coupling procedure used in the preparation of several example compounds is shown in Scheme 6 below.

##STR00097##

[0502] To an oven-dried Schlenk tube was added amine (1 mmol) and bromide (1 mmol) and toluene (3 mL). To the above homogeneous solution t-BuONa (1.5 mmol) was added. After stirring for 5 minutes, Pd.sub.2(dba).sub.3 (0.05 mmol) and Bu.sub.3P (0.075 mmol), were added under nitrogen atmosphere. The mixture was stirred for 24 h at 110° C. After cooling to r.t., the reaction mixture was diluted with ethyl acetate (50 mL) and filtered through bed of diatomaceous earth. The organic solution was dried with MgSO.sub.4, concentrated in vacuo and purified by flash column chromatography with hexane/ethyl acetate (gradient of pure hexane to 10/1 hexane/ethyl acetate) as eluent to give desired product (39-55% yield).

[0503] For Compound 3b .sup.1H NMR (500 MHz, CDCl.sub.3): δ 9.45 (s, 1H), 8.01 (s, 1H), 7.67-7.56 (d, 2H), 7.2-7.1 (m, 2H), 6.98 (s, 1H), 6.82 (s, 1H) 6.78-6.26 (m, 2H), 5.99 (s, 1H) 3.92 (s, 3H), 2.23-1.97 (m, 15H) ppm

[0504] For Compound 3e .sup.1H NMR (500 MHz, CDCl.sub.3): δ 9.46 (s, 1H), 8.05 (s, 1H), 7.79-7.56 (m, 4H), 7.2-6.99 (m, 4H), 6.98 (s, 1H, 5.99 (s, 1H) 3.94 (s, 3H), 2.23-1.97 (m, 15H) ppm

[0505] Carboxylic acid compounds were prepared by hydrolysis reactions as shown in Schemes 7, 8, 9 and 10, and the experimental procedures described below.

##STR00098##

[0506] To a solution of ester (1 mmol) in ethanol (10 mL) was added 2 mmol of 2N NaOH solution and heated at 40° C. for 24-48 h. Upon completion of the reaction, reaction was cooled on ice and acidified with 2N Hydrochloride solution and extracted three times with 10 mL of ethyl acetate. The organic solution was dried with MgSO.sub.4, concentrated in vacuo and purified by flash column chromatography with hexane/ethyl acetate (gradient of pure hexane to 5/1 hexane/ethyl acetate) as eluent to give desired product. Yield 70-79%

[0507] CP-52 was confirmed by LC-MS (ESI, M+H 439.1).

[0508] CP-57 was confirmed by LC-MS (ESI M+H 521.1).

[0509] CP-62 was confirmed by LC-MS (ESI M+H 457.1).

##STR00099##

[0510] To a solution of ester (1 mmol) in ethanol (10 mL) was added 2 mmol of 2N NaOH solution and heated at 40° C. for 24-48 h. Upon completion of the reaction, reaction was cooled on ice and acidified with 2N Hydrochloride solution and extracted three times with 10 mL of ethyl acetate. The organic solution was dried with MgSO.sub.4, concentrated in vacuo and purified by flash column chromatography with hexane/ethyl acetate (gradient of pure hexane to 5/1 hexane/ethyl acetate) as eluent to give desired product. Yield 80-83%

[0511] CP-59 was confirmed by LC-MS (ESI, M+H 509.1).

[0512] CP-65 was confirmed by LC-MS (ESI, M+H 454.1).

##STR00100##

[0513] CP-55 was confirmed by LC-MS (ESI, M+H 439.12).

[0514] CP-64 was confirmed by LC-MS (ESI, M+H 474.1).

##STR00101##

[0515] To a solution of ester (1 mmol) in ethanol (10 mL) was added 2 mmol of 2N NaOH solution and heated at 40° C. for 24-48 h. Upon completion of the reaction, reaction was cooled on ice and acidified with 2N Hydrochloride solution and extracted three times with 10 mL of ethyl acetate. The organic solution was dried with MgSO.sub.4, concentrated in vacuo and purified by flash column chromatography with hexane/ethyl acetate (gradient of pure hexane to 5/1 hexane/ethyl acetate) as eluent to give desired product. Yield 73-87%

[0516] CP-55 was confirmed by LC-MS (ESI, M+H 521.1).

[0517] CP-64 was confirmed by LC-MS (ESI, M+H 575.1).

[0518] Carboxylic acid compounds were converted to vinyl ketone compounds as shown in Scheme 11, and the experimental procedures described below.

##STR00102## ##STR00103##

[0519] The acid was converted to Weinreb amide. To a solution of acid (0.1 mmol) in dichloromethane (1 mL) was added triethylamine (0.25 mmol) followed by Weinreb amine salt (0.2 mmol), HATU (0.2 mmol) and stirred at r.t. for 16 h. After completion of the reaction, water was and added and extracted three times with 10 mL of ethyl acetate. The organic solution was dried with MgSO.sub.4, concentrated in vacuo and purified by flash column chromatography with hexane/ethyl acetate (gradient of pure hexane to 5/1 hexane/ethyl acetate) as eluent to give desired product.

[0520] An ice cooled solution of Weinreb amide (1 mmol) in anhydrous THF (10 mL) was added 4 mL of 1M solution of vinyl magnesium bromide in THF and warmed to r.t. and stirred for 4 h after completion of the reaction, quenched with 1N hydrochloride solution at 0° C. and extracted three times with 10 mL of ethyl acetate. The organic solution was dried with MgSO.sub.4, concentrated in vacuo and purified by flash column chromatography with hexane/ethyl acetate (gradient of pure hexane to 5/1 hexane/ethyl acetate) as eluent to give desired product. Yield 42-57%.

[0521] CP-55 was confirmed by LC-MS (ESI, M+H 449.14).

[0522] CP-64 was confirmed by LC-MS (ESI, M+H 449.16).

Certain exemplified compound can be synthesized and characterized as discussed below.

Intermediate-I

[0523] ##STR00104##

Step-a: Synthesis of N-(4-((3r,5r,7r)-adamantan-1-yl)phenyl) acetamide (Ia)

[0524] To a solution of acetanilide (50 g, 369 mmol, 1.0 eq.) in 1,1,2,2-tetrachloroethane (300 mL) was added 1-bromoadamantane (87.5 g, 406 mmol, 1.1 eq.) and stirred for 5 minutes. Zinc chloride anhydrous (25.1 g, 184 mmol, 0.5 eq.) was added and stirred at 100° C. for 36 h. Reaction mixture was cooled to RT and excess tetrachloroethane was removed by concentrating in vacuo. The residue was dissolved in ethyl acetate, washed with water and brine. The organic layer was dried over anhydrous Sodium sulfate, adsorbed over silica and purified by flash column chromatography to afford title product as a white solid (58 g, 58%).

[0525] .sup.1H NMR (400 MHz, DMSO-d6) δ 9.81 (s, 1H), 7.47 (d, J=8.8 Hz, 2H), 7.25 (d, J=8.8 Hz, 2H), 2.04 (bs, 2H), 2.00 (s, 3H), 1.82 (s, 6H), 1.72 (s, 6H); LC-MS: m/z 270.1 (M+H).sup.+

[0526] The below intermediates were prepared by a procedure similar to Intermediate-Ia using appropriate reactants and reagents in presence of suitable solvents and appropriate reaction conditions.

TABLE-US-00001 Intermediate CP No. Structure Analytical data 396 Ia.1 [00105] .sup.1H NMR (400 MHz, DMSO-d6) δ 9.80 (s, 1H), 7.47 (d, J = 8.8 Hz, 2H), 7.24 (d, J = 8.8 Hz, 2H), 2.13-2.11 (m, 1H), 2.00 (s, 3H), 1.65 (s, 2H), 1.49-1.32 (m, 8H), 1.17 (s, 2H), 0.84 (s, 6H). LC-MS: m/z 298.2 (M + H).sup.+

Step-b: Synthesis of N-(4-((3r,5r,7r)-adamantan-1-yl)-2-chlorophenyl)acetamide (Ib)

[0527] A solution of N-(4-((3r,5r,7r)-adamantan-1-yl)phenyl)acetamide (25 g, 92.8 mmol, 1.0 eq.) in DMF (500 mL) at 0° C. was added with N-chlorosuccinimide (13.6 g, 101 mmol, 1.1 eq.). The reaction mixture was allowed to RT and stirred for 16 h. Excess DMF was removed by concentrating in vacuo. The residue was dissolved in ethyl acetate, washed with water and brine. The organic layer was dried over anhydrous Sodium sulfate and concentrated in vacuo. The crude solid (22 g, 780%) obtained was used in next step without further purification.

[0528] .sup.1H NM/R (400 MHz, DMSO-d6) δ 9.42 (s, 1H), 7.58 (d, J=8.3 Hz, 1H), 7.37 (d, J=2.5 Hz, 1H), 7.29 (dd, J.sub.1=2.85 Hz, J.sub.2=8.8 Hz, 1H), 2.06 (bs, 6H), 1.75 (s, 6H), 1.69 (s, 6H); LC-MS: m/z 304.10 (M+H).sup.+

[0529] The below intermediates were prepared by a procedure similar to Intermediate-Ib using appropriate reactants and reagents in presence of suitable solvents and appropriate reaction conditions.

TABLE-US-00002 Intermediate CP No. Structure Analytical data 170 Ib.1 [00106] .sup.1H NMR (400 MHz, DMSO-d6) δ 8.21-8.19 (m, 1H), 7.53-7.48 (m, 2H), 7.31-7.29 (m, 1H), 2.22 (s, 3H), 2.09 (s, 3H), 1.86 (s, 6H), 1.80-1.60 (m, 6H). LC-MS: m/z 348.0 M + H).sup.+ 396 Ib.2 [00107] .sup.1H NMR (400 MHz, DMSO-d6) δ 9.42 (s, 1H), 7.58 (d, J = 8.8 Hz, 1H), 7.37 (d, J = 1.6 Hz, 1H), 7.28 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 8.4 Hz, 1H), 2.14-2.12 (m, 1H), 2.06 (s, 3H), 1.67 (s, 2H), 1.51-1.32 (m, 8H), 1.18 (s, 2H), 0.85 (s, 6H). LC-MS: m/z 332.2 (M + H).sup.+

Step-c: Synthesis of 4-((3r,5r,7r)-adamantan-1-yl)-2-chloroaniline (Intermediate-1)

[0530] To a solution of N-(4-((3r,5r,7r)-adamantan-1-yl)-2-chlorophenyl)acetamide (17 g, 56 mmol, 1.0 eq.) in methanol (150 mL), conc. HCl (150 mL) was added and refluxed at 100° C. for 8 h. Excess methanol was removed in vacuo. The white ppt. obtained was filtered off. The filtered solid was washed with a solution of Sodium bicarbonate followed by water and dried under vacuum. Desired product was obtained as a white solid (13 g, 880).

[0531] .sup.1H NMR (400 MHz, DMSO-d6) δ 7.08 (d, J.sub.1=2.4 Hz, 1H), 7.02 (dd, J.sub.1=1.9 Hz, J.sub.2=8.3 Hz, 1H), 6.73 (d, J=8.3 Hz, 1H), 5.09 (bs, 2H), 2.01 (s, 3H), 1.76 (s, 6H), 1.66 (s, 6H); LC-MS: m/z 262.2 (M+H).sup.+

[0532] The below intermediates were prepared by a procedure similar to Intermediate-I using appropriate reactants and reagents in presence of suitable solvents and appropriate reaction conditions.

TABLE-US-00003 Intermediate CP No. Structure Analytical data I.1 [00108] .sup.1H NMR (400 MHz, DMSO-d6) δ 6.99 (d, J = 8.3 Hz, 2H), 6.50 (d, J = 8.3 Hz, 1H), 4.76 (s, 2H), 2.01 (bs, 3H), 1.77 (s, 6H), 1.70 (s, 6H). LC-MS: m/z 228.1 (M + H).sup.+ 295 I.2 [00109] .sup.1H NMR (400 MHz, DMSO-d6) δ 7.06 (d, J = 8.4 Hz, 2H), 6.63 (d, J = 7.6 Hz, 2H), 6.10-6.00 (bs, 2H), 2.10 (s, 1H), 1.61 (s, 2H), 1.45-1.30 (m, 8H), 1.15 (s, 2H), 0.84 (s, 6H). LC-MS: m/z 256.2 (M + H).sup.+ 396 I.3 [00110] .sup.1H NMR (400 MHz, DMSO-d6) δ 7.19 (d, J = 2.0 Hz, 1H), 7.11 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 8.4 Hz, 1H), 6.91 (d, J = 8.4 Hz, 1H), 2.11-2.10 (m, 1H), 1.61 (s, 2H), 1.46- 1.30 (m, 8H), 1.15 (s, 2H), 0.84 (s, 6H). LC-MS: m/z 290.2 (M + H).sup.+ 170 I.4 [00111] .sup.1H NMR (400 MHz, DMSO-d6) δ 7.39-7.38 (m, 1H), 7.12-7.09 (m, 1H), 6.74-6.72 (m, 1H), 3.94 (s, 2H), 2.09 (s, 3H), 1.86 (s, 6H), 1.80-1.69 (m, 6H).

[0533] The below intermediates were prepared by a procedure similar to the ones described in literature using appropriate reactants and reagents in presence of suitable solvents and appropriate reaction conditions.

TABLE-US-00004 Intermediate Literature CP No. Structure report Analytical data 113, 132, 133 I.5 [00112] Journal of the American Chemical Society, 2000, vol. 122, 17, p. 4020-4028 .sup.1H NMR (400 MHz, DMSO-d6) δ 7.21 (d, J = 3.5 Hz, 1H), 7.19 (t, J = 3.4 Hz, 2H), 7.13 (d, J = 1.9 Hz, 2H), 7.10 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 8.3 Hz, 1H), 6.84 (d, J = 8.3 Hz, 1H), 5.40 (s, 2H), 2.23 (s, 3H). LC-MS: m/z 218.0 (M + H).sup.+ 115 I.6 [00113] Organic Letters, 2012, vol. 14, 20, p. 5306-5309 .sup.1H NMR (400 MHz, DMSO-d6) δ 7.73-7.69 (m, 1H), 7.50 (t, J = 7.3 Hz, 1H), 7.49 (t, J = 7.9 Hz, 1H), 7.30 (d, J = 5.3 Hz, 1H), 7.22 (d, J = 1.4 Hz, 1H), 7.03 (d, J = 1.0 Hz, 1H), 6.77 (d, J = 8.3 Hz, 1H), 4.11 (s, 2H). LC-MS: m/z 271.9 (M + H).sup.+ 116 I.7 [00114] Journal of Medicinal Chemistry, 2012, vol. 55, 8, p. 3923-3933 .sup.1H NMR (400 MHz, DMSO-d6) δ 7.46 (dd, J.sub.1 = 3.0 Hz, J.sub.2 = 8.8 Hz, 1H), 7.38-7.34 (m, 1H), 7.24-7.22 (m, 1H), 7.07 (d, J = 2.0 Hz, 2H), 6.61 (d, J = 4.4 Hz, 2H), 5.25 (s, 2H). LC-MS: m/z 221.9 (M + H).sup.+ 118 I.8 [00115] Journal of Medicinal Chemistry, 2009, vol. 52, 9, p. 2683-2693 .sup.1H NMR (400 MHz, DMSO-d6) δ 7.31 (d, J = 1.9 Hz, 1H), 7.28- 7.22 (m, 2H), 7.16 (dd, J.sub.1 = 2.5 Hz, J.sub.2 = 8.4 Hz, 1H), 7.05 (d, J = 8.3 Hz, 1H), 6.99-6.95 (dt, J.sub.1 = 1.0 Hz, J.sub.2 = 6.3 Hz, 1H), 6.81 (d, J = 8.3 Hz, 1H), 5.38 (s, 2H), 3.75 (s, 3H). LC-MS: m/z 233.9 (M + H).sup.+ 121 I.9 [00116] WO2015/14944, 2015, A1 .sup.1H NMR (400 MHz, DMSO-d6) δ 7.10-7.05 (m, 3H), 6.93 (d, J = 2.0 Hz, 1H), 6.86 (d, J = 8.3 Hz, 1H), 6.77 (dd, J.sub.1 = 1.4 Hz, J.sub.2 = 7.8 Hz, 1H), 5.34 (s, 2H), 1.99 (s, 6H). 122 I.10 [00117] Journal of Medicinal Chemistry, 2009, vol. 52, 9, p. 2683-2693 .sup.1H NMR (400 MHz, DMSO-d6) δ 7.51 (d, J = 7.3 Hz, 1H), 7.38- 7.32 (m, 3H), 7.26 (d, J = 2.0 Hz, 1H), 7.12 (dd, J.sub.1 = 1.9 Hz, J.sub.2 = 8.3 Hz, 1H), 6.85 (d, J = 8.4 Hz, 1H), 5.53 (s, 2H). LC- MS: m/z 238.1 (M + H).sup.+ 126 I.11 [00118] Journal of Medicinal Chemistry, 2009, vol. 52, 9, p. 2683-2693 LC-MS: m/z 232.0 (M + H).sup.+ 140 I.12 [00119] WO2012/137181, 2012, A1 .sup.1H NMR (400 MHz, DMSO-d6) δ 7.19 (t, J = 2.0 Hz, 1H), 7.10 (dd, J1 = 2.0 Hz, J2 = 8.3 Hz, 1H), 6.72 (d, J = 8.3 Hz, 1H), 5.78 (s, 1H), 5.28 (s, 2H), 2.33 (m, 2H), 1.82-1.71 (m, 4H), 0.77- 0.74 (m, 6H). 146 I.13 [00120] Journal of Medicinal Chemistry, 2002, vol. 45, 8, p. 1697-1711 .sup.1H NMR (400 MHz, DMSO-d6) δ 7.47-7.40 (m, 4H), 7.32 (d, J = 1.6 Hz, 1H), 7.25 (d, J = 7.2 Hz, 2H), 7.05 (d, J = 1.2 Hz, 1H), 6.94 (d, J = 8.4 Hz, 2H), 6.41 (d, J = 8.8 Hz, 2H). LC-MS: m/z 236.1 (M + H).sup.+ 178 I.14 [00121] U.S. Pat. No. 5,200,550 A1 .sup.1H NMR (400 MHz, DMSO-d6) δ 12.91 (bs, 1H), 7.93 (t, J = 1.2 Hz, 1H), 7.76 (d, J = 8.0 Hz, 1H), 7.64 (d, J = 8.0 Hz, 1H), 7.44 (t, J = 8.0 Hz, 1H), 2.07 (s, 3H), 1.88 (s, 6H), 1.75 (s, 6H). 177, 191, 200, I.15 [00122] Journal of the Chemical Society, Perkin Transactions 2: Physical Organic Chemistry (1972- 1999), 1976, p. 662-668 .sup.1H NMR (400 MHz, DMSO-d6) δ 7.92 (t, J = 7.8 Hz, 1H), 6.56 (t, J = 2.0 Hz, 1H), 6.49 (d, J = 7.9 Hz, 1H), 6.35 (dd, J.sub.1 = 0.9 Hz, J.sub.2 = 7.9 Hz, 1H), 4.86 (s, 2H), 2.03 (s, 3H), 1.75 (s, 6H), 1.71 (s, 6H). 193 I.16 [00123] Chemistry-A European Journal, 2011, vol. 17, 49, p. 13832-13846 .sup.1H NMR (400 MHz, DMSO-d6) δ 7.34 (d, J = 7.8 Hz, 1H), 7.24 (t, J = 0.9 Hz, 1H), 7.14 (t, J = 1.0 Hz, 1H), 7.05 (d, J = 1.0 Hz, 1H), 6.91 (d, J = 9.0 Hz, 2H), 6.60 (d, J = 8.3 Hz, 2H), 5.08 (s, 2H), 3.08 (m, 1H), 1.10 (d, J = 6.9 Hz, 6H). 287 I.17 [00124] Advanced Synthesis and Catalysis, 2007, vol. 349, 10, p. 1775-1780 LC-MS: m/z 235.2 (M + H).sup.+ 288 I.18 [00125] Journal of Medicinal Chemistry, 1997, vol. 40, 16, p. 2634-2642 .sup.1H NMR (400 MHz, CDCl3) δ 6.65-6.63 (m, 4H), 3.14 (s, 2H), 3.12 (m, 4H), 1.48 (m, 4H), 1.32 (m, 4H), 0.91 (m, 6H). 292 I.19 [00126] Antibiotics Chemotherapy, 1954, vol. 4, p. 150, 152 .sup.1H NMR (400 MHz, DMSO-d6) δ 7.05 (t, J = 7.3 Hz, 2H), 6.81 (d, J = 6.8 Hz, 2H), 6.60- 6.52 (m, 5H), 5.02 (s, 2H), 3.48 (t, J = 7.8 Hz, 2H), 1.52-1.46 (m, 2H), 1.33-1.27 (m, 2H), 0.86 (t, J = 3.9 Hz, 3H). 291, 328 I.20 [00127] WO2008/82003, 2008, A1 LC-MS: m/z 181.10 (M + H).sup.+ 309 I.21 [00128] Organic and Biomolecular Chemistry, 2006, vol. 4, 6, p. 1091- 1096 .sup.1H NMR (400 MHz, DMSO-d6) δ 7.42-7.35 (m, 4H), 2.05 (s, 3H), 1.84 (s, 6H), 1.73 (s, 6H). LC-MS: m/z 237.1 (M + H).sup.+ 318 I.22 [00129] WO2010/125390, 2010, A1 LC-MS: m/z 284.2 (M- 113).sup.+ Azetidine fragment 338 I.23 [00130] Pharmazie, 1981, vol. 36, 6, p. 400- 402 .sup.1H NMR (400 MHz, DMSO-d6) δ 7.50 (d, J = 8.0 Hz, 2H), 7.02 (s, 1H), 6.49 (d, J = 8.4 Hz, 2H), 5.50 (s, 2H), 2.03 (s, 9H), 1.64 (s, 6H). LC-MS: m/z 271.15 (M + H).sup.+ 203 I.24 [00131] Organic Letters, 2007, vol. 9, 26, p. 5397-5400 .sup.1H NMR (400 MHz, DMSO-d6) δ 8.07-8.05 (m, 1H), 7.94 (s, 1H), 7.61-7.57 (m, 2H), 7.30 (d, J = 7.2 Hz, 1H), 7.28- 7.24 (m, 1H), 7.20-7.16 (m, 2H), 4.20 (s, 2H), 3.11-3.07 (m, 1H), 1.06 (d, J = 6.8 Hz, 6H). 321 I.25 [00132] Letters in Organic Chemistry, 2016, vol. 13, 3, p. 171- 176 .sup.1H NMR (400 MHz, DMSO-d6) δ 9.83 (s, 1H), 7.22-7.21 (m, 1H), 7.12-7.10 (m, 1H), 6.90- 6.88 (m, 1H), 2.03 (s, 3H), 1.79 (s, 6H), 1.71 (s, 6H). 323 I.26 [00133] WO2015/51149, 2015, A1 .sup.1H NMR (400 MHz, DMSO-d6) δ 6.62 (d, J = 8.8 Hz, 2H), 6.48 (d, J = 8.8 Hz, 2H), 4.54 (s, 2H), 3.37 (s, 2H), 1.96 (s, 3H), 1.69-1.59 (m, 12H). 337 I.27 [00134] Letters in Organic Chemistry, 2016, vol. 13, 3, p. 171- 176 .sup.1H NMR (400 MHz, DMSO-d6) δ 7.17 (d, J = 8.8 Hz, 2H), 6.83 (d, J = 8.4 Hz, 2H), 2.98- 2.96 (m, 4H), 2.92-2.88 (m, 1H), 2.81-2.80 (m, 4H), 2.03 (s, 3H), 1.81 (s, 6H), 1.71 (s, 6H). LC-MS: m/z 297.3 (M + H).sup.+ 388 I.28 [00135] Antibiotics Chemotherapy, 1954, vol. 4, p. 150, 152 .sup.1H NMR (400 MHz, DMSO-d6) δ 7.12-7.08 (m, 2H), 6.96 (d, J = 2.0 Hz, 1H), 6.86-6.80 (m, 2H), 6.64-6.58 (m, 3H), 5.30 (s, 2H), 3.50 (t, J = 7.2 Hz, 2H), 1.51- 1.46 (m, 2H), 1.35-1.28 (m, 2H), 0.87 (t, J = 7.2 Hz, 3H). LC-MS: m/z 275.1 (M + H).sup.+ 407, 408 I.29 [00136] Tetrahedron, 1988, vol. 44, 7, p. 1893-1904 .sup.1H NMR (400 MHz, DMSO-d6) δ 7.26-7.24 (m, 4H), 3.66 (s, 2H), 2.05 (s, 3H), 1.84 (s, 6H), 1.73 (s, 6H). LC- MS: m/z 242.2 (M + H).sup.+ 314 I.30 [00137] Letters in Organic Chemistry, 2016, vol. 13, 3, p. 171- 176 .sup.1H NMR (400 MHz, DMSO-d6) δ 9.07 (s, 1H), 7.13-7.11 (m, 2H), 6.68-6.66 (m, 2H), 2.03 (s, 3H), 1.80 (s, 6H), 1.71 (s, 6H). LC-MS: m/z 228.0 (M + H).sup.+ 383 I.31 [00138] Letters in Organic Chemistry, 2016, vol. 13, 3, p. 171- 176 .sup.1H NMR (400 MHz, DMSO-d6) δ 6.87-6.83 (m, 1H), 6.65 (dd, J.sub.1 = 2.8 Hz, J.sub.2 = 8.8 Hz, 1H), 6.15 (d, J = 8.4 Hz, 1H), 2.08- 2.05 (m, 1H), 1.54 (s, 2H), 1.38-1.29 (m, 8H), 1.11 (s, 2H), 0.82 (s, 6H). LC-MS: m/z 289.05 (M − H).sup.−. 360 I.32 [00139] Chemistry-A European Journal, 2011, vol. 17, 49, p. 13832-13846 .sup.1H NMR (400 MHz, DMSO-d6) δ 10.20 (s, 1H), 7.39 (d, J = 7.9 Hz, 1H), 7.32 (t, J = 7.4 Hz, 1H), 7.19 (t, J = 6.3 Hz, 2H), 7.09 (d, J = 7.3 Hz, 1H), 7.03 (t, J = 8.3 Hz, 2H), 2.99-2.96 (m, 1H), 1.11 (d, J = 6.9 Hz, 6H). LC-MS: m/z 245.1 (M − H).sup.−. 93 I.33 [00140] Chemistry-A European Journal, 2011, vol. 17, 49, p. 13832-13846 LC-MS: m/z 246.0 (M + H).sup.+

Intermediate-II

[0534] ##STR00141##

Step-a: Synthesis of methyl 2-((4-bromophenyl)amino)benzoate (Intermediate-II)

[0535] A solution of methyl 2-iodobenzoate (30 g, 114.5 mmol, 1.0 eq.) and 4-bromoaniline (19.3 g, 114.5 mmol, 1.0 eq.) in toluene (500 mL) was added with cesium carbonate (49 g, 150 mmol, 1.3 eq.) and de-gassed with N.sub.2 gas for 15 min. Palladium acetate (1.28 g, 5.7 mmol, 0.05 eq.) and rac. BINAP (3.56 g, 5.7 mmol, 0.05 eq.) were added and de-gassed for 5 min. Reaction mass was heated at 110° C. for 16 h. Reaction mass was filtered through celite, concentrated in vacuo and purified by combi-flash to afford the title product as pale brown liquid (33 g, 940%).

[0536] .sup.1H NMR (400 MHz, DMSO-d6) δ 9.25 (s, 1H), 7.89 (dd, J.sub.1=2.0 Hz, J.sub.2=8.3 Hz, 1H), 7.51 (d, J=2.9 Hz, 2H), 7.48 (t, J=1.9 Hz, 1H), 7.26 (d, J=7.8 Hz, 1H), 7.21 (d, J=4.9 Hz, 2H), 6.87 (t, J=1.0 Hz, 1H), 3.84 (s, 3H); LC-MS: m/z 307.9 (M+H).sup.2+

[0537] The below intermediates were prepared by a procedure similar to Intermediate-II using appropriate reactants and reagents employing suitable Pd & Fe catalysts and ligands and in presence of suitable solvents and appropriate reaction conditions.

TABLE-US-00005 Intermediate CP No. Structure Analytical data  52 II.1 [00142] LC-MS: m/z 308 (M + H).sup.2+ 127 II.2 [00143] .sup.1H NMR (400 MHz, DMSO-d6) δ 10.24 (s, 1H), 8.20 (d, J = 5.6 Hz, 1H), 7.89-7.82 (m, 2H), 7.64 (t, J = 8.4 Hz, 1H), 7.27 (t, J = 7.6 Hz, 1H), 6.84 (d, J = 6.0 Hz, 1H), 3.77 (s, 3H). LC-MS: m/z 263.9 (M + H).sup.+ 141 154 II.3 [00144] .sup.1H NMR (400 MHz, DMSO-d6) δ 10.83 (s, 1H), 8.69 (s, 2H), 8.57 (d, J = 8.4 Hz, 1H), 7.98 (dd, J.sub.1 = 1.6 Hz, J.sub.2 = 8.0 Hz, 1H), 7.66-7.61 (m, 1H), 7.11 (t, J = 7.6 Hz, 1H), 3.86 (s, 3H). LC-MS: m/z 309.9 (M + H).sup.2+ 142 252 II.4 [00145] .sup.1H NMR (400 MHz, DMSO-d6) δ 10.34 (s, 1H), 8.35 (d, J = 1.6 Hz, 1H), 8.29-8.26 (m, 2H), 7.94 (dd, J.sub.1 = 1.6 Hz, J.sub.2 = 7.6 Hz, 1H), 7.60 (t, J = 8.0 Hz, 1H), 7.11 (t, J = 8.0 Hz, 1H), 3.84 (s, 3H). LC-MS: m/z 309.9 (M + H).sup.2+ 144, 152, 155 II.5 [00146] .sup.1H NMR (400 MHz, DMSO-d6) δ 10.18 (s, 1H), 8.39 (d, J = 8.8 Hz, 1H), 8.30 (d, J = 2.4 Hz, 1H), 7.92 (dd, J.sub.1 = 1.2 Hz, J2 = 7.6 Hz, 1H), 7.83 (dd, J.sub.1 = 2.4 Hz, J.sub.2 = 8.8 Hz, 1H), 7.56 (t, J = 7.2 Hz, 1H), 7.04-6.98 (m, 2H), 3.84 (s, 3H). LC-MS: m/z 308.9 (M + H).sup.2+ 158 II.6 [00147] .sup.1H NMR (400 MHz, DMSO-d6) δ 8.57 (s, 1H), 7.63 (t, J = 1.5 Hz, 1H), 7.44-7.40 (m, 4H), 7.33-7.30 (m, 1H), 7.06-7.02 (m, 2H), 3.83 (s, 3H). LC- MS: m/z 307.9 (M + H).sup.2+ 175 II.7 [00148] .sup.1H NMR (400 MHz, DMSO-d6) δ 10.72 (s, 1H), 8.52 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 4.8 Hz, 1H), 8.49 (d, J = 9.0 Hz, 1H), 8.39 (d, J =0 2.4 Hz, 1H), 8.34 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 8.0 Hz, 1H), 8.0 (dd, J.sub.1 = 2.4 Hz, J.sub.2 = 8.8 Hz, 1H), 7.06 (dd, J.sub.1 = 5.2 Hz, J.sub.2 = 8.0 Hz, 1H), 3.91 (s, 3H). LC-MS: m/z 310 (M + H).sup.2+ 194 II.8 [00149] .sup.1H NMR (400 MHz, DMSO-d6) δ 8.29 (dd, J.sub.1 = 1.6 Hz, J.sub.2 = 4.4 Hz, 1H), 7.95 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 7.2 Hz, 1H), 6.86 (dd, J.sub.1 = 5.2 Hz, J.sub.2 = 8.0 Hz, 1H), 3.82 (s, 3H), 3.42 (s, 4H), 3.29-3.25 (m, 4H). 200, 233, 241, 247 II.9 [00150] .sup.1H NMR (400 MHz, DMSO-d6) δ 10.15 (s, 1H), 8.46 (dd, J.sub.1 = 1.4 Hz, J.sub.2 = 4.9 Hz, 1H), 8.28 (dd, J.sub.1 = 1.4 Hz, J.sub.2 = 7.8 Hz, 1H), 8.20 (s, 1H), 7.56 (d, J = 7.8 Hz, 1H), 7.27 (t, J = 8.3 Hz, 1H), 7.19 (d, J = 7.8 Hz, 1H), 6.97- 6.94 (m, 1H), 3.91 (s, 3H). LC-MS: m/z 306.9 (M + H).sup.+ 218, 385, 386, 389 II.10 [00151] .sup.1H NMR (400 MHz, DMSO-d6) δ 10.13 (s, 1H), 8.44 (dd, J.sub.1 = 1.6 Hz, J.sub.2 = 4.8 Hz, 1H), 8.28 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 8.0 Hz, 1H), 7.72 (d, J = 9.2 Hz, 2H), 7.49 (d, J = 8.8 Hz, 2H), 6.95- 6.92 (m, 1H), 3.91 (s, 3H). LC-MS: m/z 307.1 (M + H).sup.+ 223 II.11 [00152] .sup.1H NMR (400 MHz, DMSO-d6) δ 9.96 (s, 1H), 8.56 (d, J = 1.0 Hz, 2H), 8.01 (s, 1H), 7.66-7.60 (m, 1H), 7.34- 7.29 (m, 2H), 7.06-7.03 (m, 1H). LC- MS: m/z 294.0 (M + H).sup.+ 242 II.12 [00153] .sup.1H NMR (400 MHz, DMSO-d6) δ 9.98 (s, 1H), 8.28-8.26 (m, 2H), 8.06- 8.04 (m, 1H), 7.92-7.89 (m, 1H), 7.72-7.68 (m, 1H), 7.28 (t, J = 0.8 Hz, 1H). LC-MS: m/z 295.0 (M + H).sup.+ 243 II.13 [00154] .sup.1H NMR (400 MHz, DMSO-d6) δ 9.67 (s, 1H), 8.3 (m, 2H), 7.59 (d, J = 8.8 Hz, 2H), 7.30 (m, 3H), 7.11 (d, J =8.8 Hz, 2H), 6.72 (d, J = 8.9 Hz, 2H), 3.85 (s, 3H). 251 II.14 [00155] .sup.1H NMR (400 MHz, DMSO-d6) δ 10.17 (s, 1H), 8.70 (d, J = 1.0 Hz, 1H), 8.38 (d, J = 2.4 Hz, 1H), 8.24 (dd, J.sub.1 = 1.9 Hz, J.sub.2 = 8.8 Hz, 1H), 7.73 (dd, J.sub.1 = 2.4 Hz, J.sub.2 = 8.3 Hz, 1H), 7.62-7.56 (m, 1H), 7.01 (t, J = 1.5 Hz, 1H), 6.88 (d, J = 8.8 Hz, 1H). LC-MS: m/z 295.9 (M + H).sup.2+ 254 II.15 [00156] .sup.1H NMR (400 MHz, DMSO-d6) δ 10.38 (s, 1H), 8.49 (dd, J.sub.1 = 1.5 Hz, J.sub.2 = 4.4 Hz, 1H), 8.31 (dd, J.sub.1 = 1.9 Hz, J.sub.2 = 7.8 Hz, 1H), 7.89-7.84 (m, 4H), 7.02-6.99 (m, 1H), 3.92 (s, 3H), 1.54 (s, 9H). 259, 346 II.16 [00157] .sup.1H NMR (400 MHz, DMSO-d6) δ 9.76 (s, 1H), 7.97 (d, J = 8.8 Hz, 2H), 7.83-7.78 (m, 3H), 7.52 (d, J = 7.3 Hz, 1H), 7.13 (d, J = 8.3 Hz, 1H), 4.37- 4.32 (m, 2H), 1.54 (s, 9H), 1.36 (t, J = 6.8 Hz, 3H). 264 II.17 [00158] .sup.1H NMR (400 MHz, DMSO-d6) δ 9.16 (s, 1H), 8.15 (dd, J.sub.1 = 1.2 Hz, J.sub.2 = 5.6 Hz, 1H), 7.69-7.66 (m, 2H), 7.59-7.55 (m, 1H), 7.42-7.39 (m, 2H), 6.82 (d, J = 8.0 Hz, 1H), 6.78-6.75 (m, 1H). LC-MS: m/z 249.0 (M + H).sup.+ 265 II.18 [00159] .sup.1H NMR (400 MHz, DMSO-d6) δ 9.30 (s, 1H), 8.11 (dd, J.sub.1 = 1.2 Hz, J.sub.2 = 8.0 Hz, 1H), 7.85 (d, J = 8.8 Hz, 2H), 7.58 (t, J = 6.8 Hz, 1H), 7.47 (d, J = 8.0 Hz, 1H), 7.30 (d, J = 8.8 Hz, 2H), 7.09-7.05 (m, 1H), 1.54 (s, 9H). LC-MS: m/z 313.0 (M − H).sup.− 269 II.19 [00160] .sup.1H NMR (400 MHz, DMSO-d6) δ 9.95 (s, 1H), 8.56-8.51 (m, 2H), 7.66- 7.64 (m, 2H), 7.54-7.52 (m, 2H), 7.02 (dd J.sub.1 = 5.2 Hz, J.sub.2 = 8.4 Hz, 1H). 274, 285, II.20 [00161] .sup.1H NMR (400 MHz, DMSO-d6) δ 9.40 (s, 1H), 7.93 (d, J = 7.8 Hz, 1H), 7.83 (d, J = 8.3 Hz, 2H), 7.53-7.44 (m, 2H), 7.26 (d, J = 8.8 Hz, 2H), 6.98 (t, J = 7.8 Hz, 1H), 3.84 (s, 3H), 1.53 (s, 9H). LC-MS: m/z 328.0 (M + H).sup.+ 302 II.21 [00162] .sup.1H NMR (400 MHz, DMSO-d6) δ 10.06 (s, 1H), 8.41 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 4.9 Hz, 1H), 8.26 (dd, J.sub.1 = 1.9 Hz, J.sub.2 = 7.8 Hz, 1H), 7.66 (d, J = 8.8 Hz, 2H), 7.21 (d, J = 8.4 Hz, 2H), 6.88 (m, 1H), 3.90 (s, 3H), 3.50 (s, 2H), 1.42 (s, 9H). LC-MS: m/z 343.0 (M + H).sup.+ 303 II.22 [00163] .sup.1H NMR (400 MHz, DMSO-d6) δ 8.93 (s, 1H), 7.78 (d, J = 8.8 Hz, 2H), 7.73 (s, 1H), 7.55-7.50 (m, 1H), 7.44 (d, J = 4.4 Hz, 2H), 7.09 (d, J = 8.8 Hz, 2H), 3.84 (s, 3H), 1.53 (s, 9H). LC-MS: m/z 328.0 (M + H).sup.+ 327 II.23 [00164] .sup.1H NMR (400 MHz, DMSO-d6) δ 9.48 (s, 1H), 7.85 (d, J = 8.8 Hz, 2H), 7.74 (t, J = 7.6 Hz, 1H), 7.47-7.42 (m, 3H), 7.05 (d, J = 8.4 Hz, 1H), 4.35- 4.30 (m, 2H), 1.35 (t, J = 7.2 Hz, 3H). LC-MS: m/z 321.0 (M + H).sup.+ 330 II.24 [00165] LC-MS: m/z 288.0 (M − 56H).sup.+; t-butyl fragment 333, 408 II.25 [00166] .sup.1H NMR (400 MHz, DMSO-d6) δ 9.31 (s, 1H), 7.96-7.90 (m, 1H), 7.72 (s, 1H), 7.59-7.57 (m, 1H), 7.50-7.44 (m, 3H), 7.25 (d, J = 8.4 Hz, 1H), 3.82 (s, 3H), 1.50 (s, 9H). LC-MS: m/z 328.2 (M + H).sup.+ 334 II.26 [00167] .sup.1H NMR (400 MHz, DMSO-d6) δ 7.91 (d, J = 9.3 Hz, 1H), 7.88 (d, J = 8.8 Hz, 2H), 7.69 (t, J = 7.8 Hz, 1H), 7.40 (t, J = 7.8 Hz, 1H), 7.20 (d, J = 8.3 Hz, 1H), 6.93 (d, J = 8.8 Hz, 2H), 3.67 (s, 3H), 1.53 (s, 9H). 347 II.27 [00168] .sup.1H NMR (400 MHz, DMSO-d6) δ 7.57 (s, 1H), 7.29 (d, J = 8.8 Hz, 2H), 7.21 (d, J = 7.6 Hz, 1H), 7.15-7.12 (m, 2H), 6.97-6.94 (m, 1H), 6.77 (d, J = 8.8 Hz, 2H), 2.17 (s, 3H). LC-MS: m/z 262.0 (M + H).sup.+ 651 II.28 [00169] LC-MS: m/z 324.05 (M + H).sup.+ 638 II.29 [00170] LC-MS: m/z 310.1 (M + H).sup.+

Intermediate-II.28

[0538] ##STR00171##

Step-a: Synthesis of methyl 2-((5-bromopyrimidin-2-yl)(tert-butoxycarbonyl)amino)benzoate (II.28)

[0539] To a solution of Intermediate-II.3 (1.3 g, 4.3 mmol, 1 eq.) in THF (30 mL), DMAP (0.1 g, 0.84 mmol, 0.2 eq.), pyridine (0.67 g, 8.7 mmol, 2 eq.), Boc anhydride (1.38 g, 6.3 mmol, 1.5 eq.) were added and heated at 60° C. overnight. Reaction mass was concentrated in vacuo and purified by combi-flash to afford title product as off-white solid (1.4 g, 82%). LC-MS: m/z 408.2 (M+H).sup.+

[0540] The below intermediates were prepared by a procedure similar to Intermediate-II.28 using appropriate reactants and reagents and in presence of suitable solvents and appropriate reaction conditions.

TABLE-US-00006 Intermediate CP No. Reactant Structure Analytical data 142 II.29 II.4 [00172] LC-MS: m/z 408.9 (M + H).sup.+ 152 II.30 II.5 [00173] LC-MS: m/z 409.9 (M + H).sup.2+ 175 II.31 II.7 [00174] LC-MS: m/z 410.1 (M + H).sup.2+

[0541] The below intermediates were prepared by a procedure similar to Intermediate-II using appropriate reactants and reagents employing suitable Pd catalysts and ligands and in presence of suitable solvents and appropriate reaction conditions.

TABLE-US-00007 Intermediate CP No. Reactant Structure Analytical data 357 II.32 Int-II [00175] LC-MS: m/z 419.1 (M + H).sup.+ 363 II.33 I.1 [00176] .sup.1H NMR (400 MHz, DMSO-d6) δ 8.28 (s, 1H), 7.6 (s, 1H), 7.33-7.25 (m, 5H), 7.04 (d, J = 8.8 Hz, 2H), 3.82 (s, 3H), 2.05 (s, 3H), 1.84 (s, 6H), 1.73 (s, 6H). LC-MS: m/z 362.3 (M + H).sup.+ 394 II.34 [00177] LC-MS: m/z 329.2 (M + H).sup.+ 315, 316 II.35 I.1 [00178] LC-MS: m/z 362.3 (M + H).sup.+

Intermediates-IIIa & IIIb

[0542] ##STR00179##

Step-a: Synthesis of ethyl 2-(5-bromo-1H-indazol-1-yl)acetate & ethyl 2-(5-bromo-2H-indazol-2-yl)acetate (IIIa & IIIb)

[0543] A solution of 5-bromo-1H-indazole (1 g, 5.1 mmol, 1.0 eq.) in acetonitrile (25 mL) was added with potassium carbonate (1.8 g, 12.8 mmol, 2.5 eq.) under stirring. Ethyl bromoacetate (0.7 mL, 6.1 mmol, 1.2 eq.) was added drop wise and reaction mass was heated at reflux overnight. Reaction mass was concentrated in vacuo, adsorbed over silica after water washings and purified by combi-flash to afford title products IIIa (400 mg, 28%, white solid) and IIIb (180 mg, 13%, yellow solid).

[0544] Intermediate-IIIa: .sup.1H NMR (400 MHz, DMSO-d6) δ 8.10 (s, 1H), 8.05 (s, 1H), 7.68-7.65 (m, 1H), 7.53-7.51 (m, 1H), 5.40 (s, 2H), 4.18-4.12 (m, 2H), 1.19 (t, J=6.8 Hz, 3H); LC-MS: m/z 283.0 (M+H).sup.+

[0545] Intermediate-IIIb: .sup.1H NMR (400 MHz, DMSO-d6) δ 8.41 (s, 1H), 8.02 (s, 1H), 7.60-7.58 (m, 1H), 7.35-7.32 (m, 1H), 5.42 (s, 2H), 4.20-4.15 (m, 2H), 1.18 (t, J=6.4 Hz, 3H); LC-MS: m/z 283.0 (M+H).sup.+

[0546] The below intermediates were prepared by a procedure similar to Intermediates-IIIa & IIIb using appropriate reactants and reagents and in presence of suitable solvents and appropriate reaction conditions.

TABLE-US-00008 Intermediate CP No. Structure Analytical data 187 III.1 [00180] .sup.1H NMR (400 MHz, DMSO-d6) δ 7.49 (d, J = 7.6 Hz, 2H), 7.25 (d, J = 8.0 Hz, 2H), 3.81 (d, J = 13.6 Hz, 1H), 3.58 (s, 3H), 3.49 (d, J = 12.4 Hz, 1H), 3.27 (dd, J.sub.1 = 5.2 Hz, J.sub.2 = 8.8 Hz, 1H), 2.85-2.80 (m, 1H), 2.38-2.32 (m, 1H), 2.09-2.04 (m, 1H), 1.84-1.71 (m, 3H). 192 III.2 [00181] .sup.1H NMR (400 MHz, DMSO-d6) δ 7.62 (s, 1H), 7.54 (d, J = 8.8 Hz, 2H), 7.15 (s, 1H), 7.11 (d, J = 8.4 Hz, 2H), 5.58 (s, 2H), 4.25- 4.23 (m, 2H), 2.50 (t, J = 2.0 Hz, 3H). LC- MS: m/z 308.9 (M + H).sup.+ 195 III.3 [00182] Proceeded with crude/only TLC reference 197 III.4 [00183] .sup.1H NMR (400 MHz, DMSO-d6) δ 8.24 (d, J = 9.2 Hz, 1H), 7.88 (dd, J.sub.1 = 1.6 Hz, J.sub.2 = 10 Hz, 1H), 7.27-7.55 (m, 1H), 7.42-7.34 (m, 1H), 5.26 (d, J = 2.8 Hz, 2H), 4.20-4.14 (m, 2H), 1.25-1.20 (m, 3H). LC-MS: m/z 282.9 (M + H).sup.+ 201 III.5 [00184] .sup.1H NMR (400 MHz, DMSO-d6) δ 8.65 (s, 1H), 7.98 (s, 1H), 7.56 (d, J = 8.4 Hz, 2H), 7.23 (d, J = 8.4 Hz, 2H), 5.4 (s, 2H). LC-MS: m/z 238 (M + H).sup.+ 202 III.6 [00185] .sup.1H NMR (400 MHz, DMSO-d6) δ 9.00 (s, 1H), 8.29 (s, 1H), 7.43-7.42 (m, 1H), 7.37- 7.35 (m, 1H), 7.22-7.19 (m, 1H), 5.47 (s, 2H), 2.05 (s, 3H), 1.84 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 372.1 (M + H).sup.+ 210 III.7 [00186] .sup.1H NMR (400 MHz, DMSO-d6) δ 8.14 (s, 1H), 8.03 (s, 1H), 7.74 (d, J = 8.4 Hz, 1H), 7.29 (dd, J.sub.1 = 1.6 Hz, J.sub.2 = 8.4 Hz, 1H), 5.38 (s, 2H), 4.14 (q, J = 14 Hz, 2H), 1.20 (t, J = 7.6 Hz, 3H). LC-MS: m/z 285.0 (M + H).sup.2+ 213 III.8 [00187] .sup.1H NMR (400 MHz, DMSO-d6) δ 8.47 (s, 1H), 7.87 (s, 1H), 7.56-7.54 (dd, J.sub.1 = 0.8 Hz, J.sub.2 = 6.4 Hz, 2H), 7.22 (d, J = 8.0 Hz, 2H), 5.35 (s, 2H), 4.23-4.18 (m, 2H), 1.26 (t, J = 7.6 Hz, 3H). LC-MS: m/z 309.0 (M + H).sup.+ 214 III.9 [00188] LC-MS: m/z 306.0 (M + H).sup.+ 217 III.10 [00189] .sup.1H NMR (400 MHz, DMSO-d6) δ 7.51-7.49 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 6.8 Hz, 2H), 7.29 (t, J = 2.0 Hz, 1H), 7.0 (d, J = 8.0 Hz, 2H), 6.91- 6.9 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 4.0 Hz, 1H), 6.20- 6.18 (dd, J.sub.1 = 1.2 Hz, J.sub.2 = 4.0 Hz, 1H), 5.51 (s, 2H), 4.16-4.11 (m, 2H), 1.12 (t, J = 6.8 Hz, 3H). LC-MS: m/z 308.0 (M + H).sup.+ 219 III.11 [00190] .sup.1H NMR (400 MHz, DMSO-d6) δ 7.70 (s, 1H), 7.51 (d, J = 2.0 Hz, 1H), 7.36 (s, 1H), 7.18-7.14 (m, 1H), 6.3 (s, 1H), 5.14 (s, 2H), 4.17-4.12 (m, 2H), 1.24-1.19 (m, 3H). LC- MS: m/z 282.1 (M + H).sup.+ 220 III.12 [00191] .sup.1H NMR (400 MHz, DMSO-d6) δ 8.01 (d, J = 0.8 Hz, 1H), 7.92 (s, 1H), 7.58 (s, 1H), 7.52 (d, J = 6.0 Hz, 1H), 7.34-7.33 (m, 2H), 5.25 (s, 2H), 3.72 (s, 3H). LC-MS: m/z 295.0 (M + H).sup.+ 221 III.13 [00192] .sup.1H NMR (400 MHz, DMSO-d6) δ 8.19 (s, 1H), 7.71 (d, J = 1.2 Hz, 1H), 7.49-7.47 (dd, J.sub.1 = 0.8 Hz, J.sub.2 = 7.6 Hz, 1H), 7.37 (s, 1H), 7.3 (t, J = 8.0 Hz, 1H), 7.13 (d, J = 7.6 Hz, 1H), 5.52 (s, 2H), 3.73 (s, 3H). LC-MS: m/z 295.1 (M + H).sup.+ 227 III.14 [00193] .sup.1H NMR (400 MHz, DMSO-d6) δ 7.74 (d, J = 1.2 Hz, 1H), 7.39-7.37 (m, 2H), 7.23 (dd, J.sub.1 = 1.6 Hz, J.sub.2 = 8.8 Hz, 1H), 6.45 (d, J = 3.2 Hz, 1H), 5.13 (s, 2H), 4.13 (q, J = 14.4 Hz, 2H), 1.2 (t, J = 7.2 Hz, 3H). LC-MS: m/z 282.0 (M + H).sup.+ 250 III.15 [00194] .sup.1H NMR (400 MHz, DMSO-d6) δ 7.51 (d, J = 8.3 Hz, 2H), 7.24 (d, J = 8.3 Hz, 2H), 3.57 (s, 3H), 3.43 (s, 2H), 2.75-2.67 (m, 1H), 2.60-2.51 (m, 1H), 2.33-2.32 (m, 1H), 2.17- 2.12 (m, 1H), 2.07-2.05 (m, 1H), 1.79-1.77 (m, 1H), 1.67-1.63 (m, 1H), 1.49-1.39 (m, 2H). LC-MS: m/z 314.0 (M + H).sup.2+

Intermediate-IV

[0547] ##STR00195##

Step-a: Synthesis of methyl 2-(4-bromobenzamido)benzoate (Intermediate-IV)

[0548] A solution of methyl 2-aminobenzoate (5 g, 33.1 mmol, 1.0 eq.) in DCM (50 mL) was added with triethylamine (11 g, 108 mmol, 3 eq.) followed by 4-bromobenzoyl chloride (7.2 g, 33.1 mmol, 1.0 eq.) and stirred at RT overnight. Reaction mixture was extracted with ethyl acetate from water and concentrated in vacuo. The crude was washed with n-pentane and dried to afford title product (9 g, 85%).

[0549] .sup.1H NMR (400 MHz, DMSO-d6) δ 11.52 (s, 1H), 8.47 (d, J=8.3 Hz, 1H), 8.04 (d, J=8.4 Hz, 1H), 7.89 (d, J=8.8 Hz, 2H), 7.83 (d, J=8.8 Hz, 2H), 7.67 (t, J=7.3 Hz, 1H), 7.24 (t, J=7.3 Hz, 1H), 3.87 (s, 3H).

[0550] The below intermediates were prepared by a procedure similar to Intermediate-IV using appropriate reactants and reagents and in presence of suitable solvents and appropriate reaction conditions.

TABLE-US-00009 Intermediate CP No. Structure Analytical data 178 IV.1 [00196] LC-MS: m/z 387.4 (M + H).sup.+ 239 IV.2 [00197] .sup.1H NMR (400 MHz, DMSO-d6) δ6 13.10 (bs, 1H), 10.63 (s, 1H), 7.58 (d, J = 5.4 Hz, 2H), 7.47 (d, J = 6.8 Hz, 2H), 1.44 (s, 4H). LC-MS: m/z 284.0 (M + H).sup.+ 291 IV.3 [00198] LC-MS: m/z 345.0 (M + H).sup.+ 317 IV.4 [00199] Proceeded with crude/only TLC reference 328 IV.5 [00200] LC-MS: m/z 345.0 (M + H).sup.2+

Intermediate-V

[0551] ##STR00201##

Step-a: Synthesis of methyl 2-((4-bromophenyl)(methyl)amino)nicotinate (Intermediate-V)

[0552] A solution of Intermediate-II.10 (0.4 g, 1.3 mmol, 1.0 eq.) in DMF (3 mL) was added with sodium hydride (50% o, 0.16 g, 3.9 mmol, 3 eq.) and stirred for 10 min. Iodomethane (0.25 mL, 3.9 mmol, 3 eq.) was added drop wise and stirred at RT overnight in a seal tube. Reaction mass was poured in to water, extracted with ethyl acetate and concentrated in vacuo. The crude was purified by combi-flash to afford title product as a colourless liquid (0.21 g, 500%).

[0553] .sup.1H NM/R (400 MHz, DMSO-d6) δ 8.46 (dd, J.sub.1=2.0 Hz, J.sub.2=4.0 Hz, 1H), 7.85 (dd, J.sub.1=2.0 Hz, J.sub.2=7.6 Hz, 1H), 7.44-7.40 (m, 2H), 7.05 (dd, J.sub.1=3.6 Hz, J.sub.2=7.2 Hz, 1H), 6.94-6.90 (m, 2H), 3.44 (s, 3H), 3.29 (s, 3H), LC-MS: m/z 321.0 (M+H).sup.+

[0554] The below intermediates were prepared by a procedure similar to Intermediate-V using appropriate reactants and reagents and in presence of suitable solvents and appropriate reaction conditions.

TABLE-US-00010 Intermediate CP No. Reactant Structure Analytical data 241 V.1 II.9 [00202] .sup.1H NMR (400 MHz, DMSO- d6) δ8.49-8.48 (m, 1H), 7.89- 7.87 (m, 1H), 7.21-7.14 (m, 2H), 7.11-7.07 (m, 2H), 6.94- 6.91 (m, 1H), 3.43 (s, 3H), 3.32 (s, 3H). LC-MS: m/z 321.0 (M + H).sup.+ 239 V.2 IV.2 [00203] .sup.1H NMR (400 MHz, DMSO- d6) δ 7.6 (d, J = 8.3 Hz, 2H), 7.27 (d, J = 6.8 Hz, 2H), 3.39 (s, 3H), 3.19 (s, 3H), 1.38 (m, 2H), 1.07 (s, 2H). 252 V.3 II.4 [00204] .sup.1H NMR (400 MHz, DMSO- d6) δ 8.19 (d, J = 1.6 Hz, 1H), 7.92 (dd, J.sub.1 = 1.6 Hz, J.sub.2 = 8.0 Hz, 1H), 7.72-7.63 (m, 1H), 7.57 (s, 1H), 7.52-7.47 (m, 2H), 3.62 (s, 3H), 3.30 (s, 3H). LC-MS: m/z 323.9 (M + H).sup.2+ 255 V.4 II.20 [00205] .sup.1H NMR (400 MHz, DMSO- d6) δ 7.90-7.80 (m, 1H), 7.80- 7.70 (m, 1H), 7.65 (d, J = 9.6 Hz, 2H), 7.50-7.40 (m, 2H), 6.48 (d, J = 9.2 Hz, 2H), 3.56 (s, 3H), 3.25 (s, 3H), 1.50 (s, 9H). LC-MS: m/z 342.1 (M + H).sup.+ 258 V.5 II.15 [00206] .sup.1H NMR (400 MHz, DMSO- d6) δ 8.57 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 4.9 Hz, 1H), 8.00 (dd, J.sub.1 = 1.9 Hz, J.sub.2 = 7.8 Hz, 1H), 7.73 (d, J = 9.3 Hz, 2H), 7.23 (m, 1H), 6.89 (d, J = 8.8 Hz, 2H), 3.45 (s, 3H), 3.32 (s, 3H), 1.52 (s, 9H). 317 V.6 IV.4 [00207] LC-MS: m/z 344.9 (M + H).sup.+2 353 V.7 II.25 [00208] .sup.1H NMR (400 MHz, DMSO- d6) δ 7.79 (d, J = 7.2 Hz, 1H), 7.68 (t, J = 8.0 Hz, 1H), 7.43- 7.36 (m, 2H), 7.25-7.21 (m, 2H), 7.04 (s, 1H), 6.75 (d, J = 6.8 Hz, 1H), 3.54 (s, 3H), 3.22 (s, 3H), 1.49 (s, 9H). LC- MS: m/z 342.1 (M + H).sup.+ 340 V.8 Int-IV [00209] .sup.1H NMR (400 MHz, DMSO- d6) δ 7.67 (d, J = 7.6 Hz, 1H), 7.60-7.58 (m, 1H), 7.52 (d, J = 8.0 Hz, 1H), 7.38-7.36 (m, 3H), 7.08 (d, J = 8.0 Hz, 2H), 3.78 (s, 3H), 3.29 (s, 3H). LC- MS: m/z 348.0 (M + H).sup.+ 357 V.9 II.32 [00210] .sup.1H NMR (400 MHz, DMSO- d6) δ 7.69 (d, J = 8.0 Hz, 1H), 7.65-7.60 (m, 1H), 7.39-7.30 (m, 3H), 7.15-7.07 (m, 3H), 6.94 (d, J = 8.8 Hz, 2H), 6.76 (d, J = 8.0 Hz, 1H), 6.60 (d, J = 8.8 Hz, 2H), 3.56 (s, 3H), 3.22 (s, 3H), 3.18 (s, 3H), 2.03 (s, 9H), 1.64 (s, 6H). 318 V.10 Int-II [00211] LC-MS: m/z 367.9 (M + H).sup.+

Intermediate-VI

[0555] ##STR00212##

Step-a: Synthesis of methyl 2-((4-((4-((3R,5R)-adamantan-1-yl)phenyl)amino) phenyl) amino) benzoate (Intermediate-VI)

[0556] A solution of Intermediate-II (0.5 g, 1.63 mmol, 1.0 eq.) and Intermediate-I.1 (0.37 g, 1.63 mmol, 1.0 eq.) in toluene (10 mL) was de-gassed with N.sub.2 gas for 15 min. Pd.sub.2dba.sub.3 (0.12 g, 0.13 mmol, 0.08 eq.) and XPhos (0.16 g, 0.326 mmol, 0.2 eq.) were added and de-gassed for 5 min. Reaction mass was heated at 110° C. for 16 h. Reaction mass was filtered through celite, concentrated in vacuo and purified by combi-flash to afford the title product as pale yellow solid (0.26 g, 35%).

[0557] .sup.1H NMR (400 MHz, DMSO-d6) δ 9.14 (s, 1H), 8.02 (s, 1H), 7.86 (dd, J.sub.1=1.4 Hz, J.sub.2=7.8 Hz, 1H), 7.35 (t, J=1.4 Hz, 1H), 7.21 (d, J=8.8 Hz, 2H), 7.12-6.96 (m, 7H), 6.69 (t, J=6.8 Hz, 1H), 3.85 (s, 3H), 2.04 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H); LC-MS: m/z 452.4 (M+H).sup.+

[0558] The below intermediates were prepared by a procedure similar to Intermediate-VI using appropriate reactants and reagents employing suitable Pd catalysts and ligands and in presence of suitable solvents and appropriate reaction conditions.

TABLE-US-00011 Inter- medi- ate CP No. Reactant Structure Analytical data 64 VI.1 Int-II & Int-I [00213] .sup.1H NMR (400 MHz, DMSO-d6) δ 9.17 (s, 1H), 7.86 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 9.8 Hz, 1H), 7.54 (s, 1H), 7.36-7.34 (m, 2H), 7.20 (s, 2H), 7.13 (d, J = 8.8 Hz, 2H), 6.06 (s, 1H), 7.03 (d, J = 4.9 Hz, 1H), 7.01 (s, 1H), 6.72 (t, J = 6.8 Hz, 1H), 3.85 (s, 3H), 2.05 (bs, 3H), 1.84 (bs, 6H), 1.31 (bs, 6H). LC-MS: m/z 487.2 (M + H).sup.+ 93 VI.2 Int-II & I.33 [00214] .sup.1H NMR (400 MHz, DMSO-d6) δ 9.22 (s, 1H), 7.89-7.87 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 8.4 Hz, 1H), 7.71 (s, 1H), 7.42- 7.23 (m, 6H), 7.21-7.19 (m, 4H), 7.15-7.07 (m, 3H), 6.74 (t, J = 7.3 Hz, 1H), 3.86 (s, 3H), 3.06- 3.02 (m, 1H), 1.14 (d, J = 12.8 Hz, 6H). LC- MS: m/z 471.1 (M + H).sup.+ 113 VI.3 Int-II & I.5 [00215] .sup.1H NMR (400 MHz, DMSO-d6) δ 9.22 (s, 1H), 7.89-7.87 (dd, J.sub.1 = 1.5 Hz, J.sub.2 = 7.9 Hz, 1H), 7.72 (s, 1H), 7.38- 7.37 (m, 2H), 7.29-7.17 (m, 10H), 7.08 (d, J = 8.3 Hz, 1H), 6.75 (d, J = 8.3 Hz, 1H), 3.86 (s, 3H), 2.27 (s, 3H). LC-MS: m/z 442.4 (M + H).sup.+ 115 VI.4 Int-II & I.6 [00216] .sup.1H NMR (400 MHz, DMSO-d6) δ 9.40 (s, 1H), 7.96 (d, J = 8.3 Hz, 1H), 7.73 (d, J = 7.9 Hz, 1H), 7.54 (d, J = 7.3 Hz, 1H), 7.48-7.45 (m, 1H), 7.34-7.32 (m, 1H), 7.31 (d, J = 8.8 Hz, 1H), 7.25 (d, J = 3.9 Hz, 1H), 7.24- 7.18 (m, 6H), 7.10 (d, J = 9.3 Hz, 1H), 6.72- 6.68 (m, 1H), 6.18 (s, 1H), 3.91 (s, 3H). LC- MS: m/z 497.1 (M + H).sup.+ 116 VI.5 Int-II & I.7 [00217] .sup.1H NMR (400 MHz, DMSO-d6) δ 9.20 (s, 1H), 8.34 (s, 1H), 7.87 (d, J = 6.8 Hz, 1H), 7.51 (dd, J.sub.1 = 2.4 Hz, J.sub.2 = 8.8 Hz, 1H), 7.45 (t, J = 6.4 Hz, 1H), 7.36 (t, J = 7.3 Hz, 1H), 7.30-7.25 (m, 3H), 7.17 (s, 4H), 7.11 (d, J = 8.8 Hz, 2H), 7.04 (d, J = 8.4 Hz, 1H), 6.73 (t, J = 7.3 Hz, 1H), 3.85 (s, 3H). 118 VI.6 Int-II & I.8 [00218] .sup.1H NMR (400 MHz, DMSO-d6) δ 9.22 (s, 1H), 7.89-7.87 (dd, J.sub.1 = 1.5 Hz, J.sub.2 = 7.9 Hz, 1H), 7.71 (s, 1H), 7.53 (d, J = 1.9 Hz, 1H), 7.41- 7.36 (m, 1H), 7.34-7.29 (dd, J.sub.1 = 1.9 Hz, J.sub.2 = 8.3 Hz, 3H), 6.24 (d, J = 8.3 Hz, 1H), 7.21-7.15 (m, 4H), 7.09 (t, J = 9.3 Hz, 2H), 7.01 (t, J = 7.4 Hz, 1H), 6.76-6.72 (dd, J.sub.1 = = 1.0 Hz, J.sub.2 = 8.3 Hz, 1H), 3.86 (s, 3H), 3.79 (s, 3H). LC-MS: m/z 458.3 (M + H).sup.+ 121 VI.7 Int-II & I.9 [00219] .sup.1H NMR (400 MHz, DMSO-d6) δ 9.22 (s, 1H), 7.91-7.87 (m, 1H), 7.69 (s, 1H), 7.50 (d, J = 8.8 Hz, 1H), 7.38- 7.36 (m, 1H), 7.30-7.06 (m, 8H), 6.99-6.96 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 8.3 Hz, 1H), 6.88-6.80 (m, 1H), 6.74 (t, J = 6.8 Hz, 1H), 3.86 (s, 3H), 2.03 (s, 6H). LC-MS: m/z 457.1 (M + H).sup.+ 122 VI.8 Int-II & I.10 [00220] .sup.1H NMR (400 MHz, DMSO-d6) δ 9.24 (s, 1H), 7.88 (d, J = 7.9 Hz, 1H), 7.78 (s, 1H), 7.55 (d, J = 7.3 Hz, 1H), 7.49 (s, 1H), 7.43-7.37 (m, 4H), 7.26 (s, 2H), 7.21 (s, 4H), 7.1 (d, J = 8.3 Hz, 1H), 6.75 (t, J = 7.3 Hz, 1H), 3.86 (s, 3H). LC-MS: m/z 463.1 (M + H).sup.+ 125 VI.9 Int-I [00221] LC-MS: m/z 396.3 (M + H).sup.+ 126 VI.10 Int-II & I.11 [00222] .sup.1H NMR (400 MHz, DMSO-d6) δ 9.21 (s, 1H), 7.87 (d, J = 1.5 Hz, 1H), 7.62 (s, 1H), 7.35 (t, J = 6.8 Hz, 1H), 7.29- 7.06 (m, 11H), 6.73 (t, J = 7.3 Hz, 1H), 3.86 (s, 3H), 2.05 (s, 3H), 1.90 (s, 3H). LC-MS: m/z 457.1 (M + H).sup.+ 135 VI.11 Int-II [00223] .sup.1H NMR (400 MHz, DMSO-d6) δ 9.39 (s, 1H), 8.26 (s, 1H), 7.99- 7.92 (m, 4H), 7.70 (d, J = 8.4 Hz, 2H), 7.55-7.46 (m, 4H), 7.38-7.33 (m, 2H), 6.89 (t, J = 8.0 Hz, 1H), 3.87 (s, 3H). LC- MS: m/z 387.0 (M + H).sup.+ 140 VI.12 Int-II & I.12 [00224] .sup.1H NMR (400 MHz, DMSO-d6) δ 9.19 (s, 1H), 7.87 (d, J = 7.9 Hz, 1H), 7.65 (s, 1H), 7.43 (s, 1H), 7.36 (t, J = 6.8 Hz, 1H), 7.27 (d, J = 6.8 Hz, 1H), 7.19-7.03 (m, 6H), 6.74 (t, J = 7.3 Hz, 1H), 5.92 (s, 1H), 3.85 (s, 3H), 2.35 (m, 2H), 1.75 (m, 4H), 0.99 (m, 6H). LC-MS: m/z 460.3 (M + H).sup.+ 141 VI.13 II.28 & Int-I [00225] .sup.1H NMR (400 MHz, DMSO-d6) δ 8.36 (s, 2H), 8.02 (s, 1H), 7.87 (dd, J.sub.1 = 1.2 Hz, J.sub.2 = 4.8 Hz, 1H), 7.55-7.53 (m, 1H), 7.41-7.38 (m, 2H), 7.24-7.19 (m, 2H), 7.12- 7.10 (m, 1H), 3.74 (s, 3H), 2.05 (s, 3H), 1.82 (s, 6H), 1.72 (s, 6H), 1.34 (s, 9H). 142 VI.14 II.29 & Int-I [00226] .sup.1H NMR (400 MHz, DMSO-d6) δ 8.81 (s, 1H), 8.28 (s, 1H), 8.05 (d, J = 1.2 Hz, 1H), 7.87- 7.85 (m, 1H), 7.76 (d, J = 8.4 Hz, 1H), 7.58- 7.54 (m, 1H), 7.41-7.38 (m, 2H), 7.32-7.28 (m, 2H), 3.77 (s, 3H), 2.05 (s, 3H), 1.85 (s, 6H), 1.73 (s, 6H). LC-MS: m/z 589.1 (M + H).sup.+ 144, 152 VI.15 II.30 & Int-I [00227] .sup.1H NMR (400 MHz, DMSO-d6) δ 7.96 (d, J = 3.2 Hz, 1H), 7.84 (dd, J.sub.1 = 1.2 Hz, J.sub.2 = 7.6 Hz, 1H), 7.79 (s, 1H), 7.56 (t, J = 2.0 Hz, 1H), 7.47- 7.46 (m, 1H), 7.41-7.35 (m, 3H), 7.27 (dd, J.sub.1 = 1.2 Hz, J.sub.2 = 8.0 Hz, 1H), 7.21 (d, J = 2.8 Hz, 1H), 7.15 (d, J = 8.0 Hz, 1H), 3.75 (s, 3H), 2.04 (s, 3H), 1.82 (s, 6H), 1.72 (s, 6H), 1.32 (s, 9H). LC- MS: m/z 588.1 (M + H).sup.+ 158 VI.16 II.6 & Int-I [00228] .sup.1H NMR (400 MHz, DMSO-d6) δ 8.17 (s, 1H), 7.37-7.04 (m, 12H), 3.82 (bs, 3H), 2.04 (s, 3H), 1.85 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 487.1 (M + H).sup.+ 170 VI.17 I.4 [00229] .sup.1H NMR (400 MHz, DMSO-d6) δ 10.25 (s, 1H), 8.41 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 4.4 Hz, 1H), 8.35 (d, J = 8.8 Hz, 1H), 8.30 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 8.0 Hz, 1H), 7.56 (d, J = 2.0 Hz, 1H), 7.37 (dd, J.sub.1 = 1.6 Hz, J.sub.2 = 8.8 Hz, 1H), 6.95 (dd, J.sub.1 = 4.4 Hz, J.sub.2 = 8.0 Hz, 1H), 3.92 (s, 3H), 2.06 (s, 3H), 1.86 (s, 6H), 1.74 (s, 6H). 173 VI.18 Int-I [00230] .sup.1H NMR (400 MHz, DMSO-d6) δ 7.43 (d, J = 10.4 Hz, 2H), 7.32 (d, J = 2.0 Hz, 1H), 7.18- 7.17 (m, 2H), 7.08 (d, J = 8.4 Hz, 2H), 6.93 (d, J = 8.4 Hz, 2H), 4.1 (m, 1H), 3.61 (d, J = 2.4 Hz, 4H), 2.90 (m, 2H), 2.80 (m, 1H), 2.05 (s, 3H), 1.83 (s, 6H), 1.73 (s, 6H), 1.34-1.30 (m, 15H). 175 VI.19 II.31 & Int-I [00231] .sup.1H NMR (400 MHz, DMSO-d6) δ 8.55 (d, J = 2.8 Hz, 1H), 8.28 (d, J = 6.0 Hz, 1H), 7.92 (s, 1H), 7.77 (s, 1H), 7.46- 7.42 (m, 3H), 7.36 (d, J = 1.6 Hz, 1H), 7.23 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 8.8 Hz, 1H), 7.15 (d, J = 8.4 Hz, 1H), 3.78 (s, 3H), 2.04 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H), 1.34 (s, 9H). LC-MS: m/z 589.1 (M + H).sup.+ 177 VI.20 I.15 [00232] .sup.1H NMR (400 MHz, DMSO-d6) δ 10.06 (s, 1H), 8.41 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 4.9 Hz, 1H), 8.26 (dd, J.sub.1 = 1.9 Hz, J.sub.2 = 7.8 Hz, 1H), 7.68 (d, J = 6.8 Hz, 1H), 7.50 (s, 1H), 7.26 (t, J = 7.8 Hz, 1H), 7.05 (d, J = 7.9 Hz, 1H), 6.88-6.85 (m, 1H), 3.90 (s, 3H), 2.06 (s, 3H), 1.88 (s, 6H), 1.74 (s, 6H). LC-MS: m/z 363.1 (M + H).sup.+ 185 VI.21 IIIa & Int-I [00233] LC-MS: m/z 464.3 (M + H).sup.+ 187 VI.22 III.1 & Int-I [00234] .sup.1H NMR (400 MHz, DMSO-d6) δ 7.77 (s, 1H), 7.33 (s, 1H), 7.18 (s, 2H), 7.12 (d, J = 8.4 Hz, 2H), 6.95 (d, J = 8.8 Hz, 2H), 3.78-3.72 (m, 1H), 3.56 (s, 3H), 3.43- 3.39 (m, 1H), 3.25-3.21 (m, 1H), 2.89-2.80 (m, 1H), 2.38-2.32 (m, 1H), 2.09-2.01 (m, 4H), 1.89- 1.81 (m, 7H), 1.82-1.69 (m, 8H). 192 VI.23 III.2 & Int-I [00235] .sup.1H NMR (400 MHz, DMSO-d6) δ 7.61 (s, 1H), 7.57 (s, 1H), 7.34 (s, 1H), 7.19 (d, J = 0.8 Hz, 2H), 7.10-7.08 (m, 3H), 6.94 (d, J = 8.4 Hz, 2H), 5.49 (s, 2H), 4.31- 4.25 (m, 2H), 2.04 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H), 1.28 (t, J = 6.8 Hz, 3H). 197 VI.24 III.4 & Int-I [00236] LC-MS: m/z 464.1 (M + H).sup.+ 199 VI.25 IIIb & Int-I [00237] LC-MS: m/z 464.1 (M + H).sup.+ 200 VI.26 II.9 & I.15 [00238] .sup.1H NMR (400 MHz, DMSO-d6) δ 10.09 (s, 1H), 8.38 (t, J = 1.4 Hz, 1H), 8.25 (d, J = 7.8 Hz, 1H), 8.12 (s, 1H), 7.66 (s, 1H), 7.19-7.11 (m, 3H), 7.02 (d, J = 7.8 Hz, 1H), 6.95 (d, J = 7.8 Hz, 1H), 6.89-6.83 (m, 2H), 6.70 (d, J = 7.8 Hz, 1H), 3.89 (s, 3H), 2.04 (s, 3H), 1.75 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 454.3 (M + H).sup.+ 210 VI.27 III.7 & Int-I [00239] .sup.1H NMR (400 MHz, DMSO-d6) +67 7.91 (s, 1H), 7.77 (s, 1H), 7.58 (d, J = 8.4 Hz, 1H), 7.37 (d, J = 2.0 Hz, 1H), 7.32 (d, J = 8.8 Hz, 1H), 7.23- 7.21 (m, 1H), 6.99 (s, 1H), 6.92 (d, J = 8.0 Hz, 1H), 5.19 (s, 2H), 4.12 (q, J = 14 Hz, 2H), 2.05 (s, 3H), 1.85 (s, 6H), 1.73 (s, 6H), 1.17 (t, J = 6.8 Hz, 3H). LC-MS: m/z 464.2 (M + H).sup.+ 213 VI.28 III.8 & Int-I [00240] .sup.1H NMR (400 MHz, DMSO-d6) δ 8.38 (s, 1H), 7.85 (s, 1H), 7.64 (s, 1H), 7.34 (s, 1H), 7.21 (s, 2H), 7.17 (d, J = 8.4 Hz, 2H), 6.94 (d, J = 8.4 Hz, 2H), 5.24 (s, 2H), 4.23-4.17 (q, J = 3.6 Hz, 2H), 2.04 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H), 1.25 (t, J = 7.2 Hz, 3H). 214 VI.29 III.9 & Int-I [00241] .sup.1H NMR (400 MHz, DMSO-d6) δ 8.69-8.68 (m, 1H), 8.15-8.13 (m, 1H), 7.41-7.39 (m, 2H), 7.30 (d, J = 2.0 Hz, 1H), 7.15-7.14 (m, 2H), 7.12- 7.03 (m, 3H), 6.94-6.89 (m, 1H), 4.34 (s, 2H), 3.83 (s, 3H), 2.03 (s, 3H), 1.81 (s, 6H), 1.71 (s, 6H). LC-MS: m/z 487.2 (M + H).sup.+ 217 VI.30 III.10 & Int-I [00242] .sup.1H NMR (400 MHz, DMSO-d6) δ 7.54 (s, 1H), 7.32 (s, 1H), 7.24 (t, J = 2.0 Hz, 1H), 7.17 (s, 2H), 7.01 (d, J = 8.4 Hz, 2H), 6.93 (d, J = 8.0 Hz, 2H), 6.88-6.87 (m, 1H), 6.15-6.14 (m, 1H), 5.43 (s, 2H), 4.20-4.15 (q, J = 7.2 Hz, 2H), 2.04 (s, 3H), 1.82 (s, 6H), 1.72 (s, 6H), 1.23 (t, J = 6.8 Hz, 3H). LC-MS: m/z 489.2 (M + H).sup.+ 218 VI.31 Int-V & Int-I [00243] .sup.1H NMR (400 MHz, DMSO-d6) δ 8.36-8.34 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 4.8 Hz, 1H), 7.71-7.67 (m, 1H), 7.5 (s, 1H), 7.32 (d, J = 1.6 Hz, 1H), 7.22- 7.19 (dd, J.sub.1 = 2.4 Hz, J.sub.2 = 8.8 Hz, 1H), 7.12 (d, J = 8.4 Hz, 1H), 6.95- 6.80 (m, 5H), 3.37 (s, 3H), 3.29 (s, 3H), 2.04 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 502.2 (M +H).sup.+ 219 VI.32 III.11 & Int-I [00244] .sup.1H NMR (400 MHz, DMSO-d6) δ 7.44 (d, J = 8.0 Hz, 1H), 7.29 (s, 2H), 7.20 (d, J = 2.8 Hz, 1H), 7.09-7.06 (m, 3H), 6.87 (dd, J.sub.1 = 1.6 Hz, J.sub.2 = 8.4 Hz, 1H), 6.37 (d, J = 2.8 Hz, 1H), 5.11 (s, 2H), 4.16-4.12 (m, 2H), 2.03 (s, 3H), 1.81 (d, J = 2.8 Hz, 6H), 1.71 (s, 6H), 1.19 (t, J = 7.2 Hz, 3H). LC-MS: m/z 463.2 (M + H).sup.+ 220 VI.33 III.12 & Int-I [00245] .sup.1H NMR (400 MHz, DMSO-d6) δ 7.93 (d, J = 0.8 Hz, 1H), 7.85 (d, J = 0.8 Hz, 1H), 7.67 (s, 1H), 7.34 (s, 1H), 7.19 (t, J = 7.2 Hz, 3H), 6.89 (d, J = 8.4 Hz, 2H), 6.74 (d, J = 8.0 Hz, 1H), 5.17 (s, 2H), 3.72 (s, 3H), 2.05 (s, 3H), 1.83 (s, 6H), 1.73 (s, 6H). LC- MS: m/z 476.2 (M + H).sup.+ 221 VI.34 III.13 & Int-I [00246] .sup.1H NMR (400 MHz, DMSO-d6) δ 8.10 (s, 1H), 7.69 (s, 1H), 7.64 (s, 1H), 7.34 (d, J = 2.0 Hz, 1H), 7.21-7.13 (m, 3H), 6.85 (d, J = 8.4 Hz, 1H), 6.77 (s, 1H), 6.61 (d, J = 8.0 Hz, 1H), 5.45 (s, 2H), 3.73 (s, 3H), 2.05 (s, 3H), 1.84 (s, 6H), 1.73 (s, 6H). LC- MS: m/z 476.3 (M + H).sup.+ 227 VI.35 III.14 & Int-I [00247] LC-MS: m/z 463.2 (M + H).sup.+ 233 VI.36 II.9 & Int-I [00248] .sup.1H NMR (400 MHz, DMSO-d6) δ 10.03 (s, 1H), 8.38 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 4.9 Hz, 1H), 8.24 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 7.8 Hz, 1H), 7.56 (s, 1H), 7.48 (s, 1H), 7.32 (m, 2H), 7.23 (m, 1H), 7.14 (m, 2H), 6.88 (m, 1H), 6.68 (m, 1H), 3.90 (s, 3H), 2.08 (s, 3H), 1.85 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 488.2 (M + H).sup.+ 239 VI.37 V.2 & Int-I [00249] .sup.1H NMR (400 MHz, DMSO-d6) δ 7.74 (s, 1H), 7.36 (s, 1H), 7.23 (m, 2H), 7.1 (d, J = 8.8 Hz, 2H), 6.95 (d, J = 8.8 Hz, 2H), 3.41 (s, 3H), 3.15 (s, 3H), 2.05 (bs, 3H), 1.84 (bs, 6H), 1.72 (bs, 6H), 1.3 (m, 2H), 1.05 (m, 2H). LC-MS: m/z 493.2 (M + H).sup.+ 241 VI.38 V.1 & Int-I [00250] .sup.1H NMR (400 MHz, DMSO-d6) δ 8.39 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 4.8 Hz, 1H), 7.79 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 8.0 Hz, 1H), 7.54 (s, 1H), 7.32 (d, J = 2.0 Hz, 1H), 7.25 (d, J = 8.4 Hz, 1H), 7.18 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 8.4 Hz, 1H), 7.10 (t, J = 8.0 Hz, 1H), 6.95 (dd, J.sub.1 = 3.2 Hz, J.sub.2 = 7.6 Hz, 1H), 6.66 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 8.4 Hz, 1H), 6.60 (t, J = 2.0 Hz, 1H), 6.46 (dd, J.sub.1 = 1.6 Hz, J.sub.2 = 7.6 Hz, 1H), 3.39 (s, 3H), 3.31 (s, 3H), 2.04 (s, 3H), 1.82 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 502.1 (M + H).sup.+ 243 VI.39 II.13 & Int-I [00251] .sup.1H NMR (400 MHz, DMSO-d6) δ 8.29 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 4.9 Hz, 1H), 8.25 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 7.3 Hz, 1H), 7.54 (s, 1H), 7.34 (s, 1H), 7.22 (m, 3H), 7.04 (d, J = 9.3 Hz, 2H), 6.99 (d, J = 9.2 Hz, 2H), 3.86 (s, 3H), 2.05 (s, 3H), 1.84 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 489.0 (M + H).sup.+ 245 VI.40 Int-V & I.1 [00252] .sup.1H NMR (400 MHz, DMSO-d6) δ 8.33 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 4.8 Hz, 1H), 7.97 (s, 1H), 7.65 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 7.2 Hz, 1H), 7.2 (d J = 8.8 Hz, 2H), 6.97-6.94 (m, 4H), 6.89-6.82 (m, 3H), 3.35 (s, 3H), 3.27 (s, 3H), 2.04 (s, 3H), 1.82 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 468.1 (M + H).sup.+ 247 VI.41 II.9 & I.1 [00253] .sup.1H NMR (400 MHz, DMSO-d6) δ 10.03 (s, 1H), 8.41 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 4.4 Hz, 1H), 8.25 (dd, J.sub.1 = 1.9 Hz, J.sub.2 = 7.8 Hz, 1H), 8.05 (s, 1H), 7.56 (t, J = 2.0 Hz, 1H), 7.24 (d, J = 8.4 Hz, 2H), 7.15 (t, J = 7.8 Hz, 1H), 7.13 (d, J = 7.8 Hz, 2H), 7.06 (d, J = 8.8 Hz, 1H), 6.88 (m, 1H), 6.71 (dd, J.sub.1 = 1.5 Hz, J.sub.2 = 7.8 Hz, 1H), 3.89 (s, 3H), 2.04 (bs, 3H), 1.84 (s, 6H), 1.73 (s, 6H). 250 VI.42 III.15 & Int-I [00254] .sup.1H NMR (400 MHz, DMSO-d6) δ 7.48 (s, 1H), 7.33 (s, 1H), 7.19 (d, J = 1.0 Hz, 2H), 7.12 (d, J = 8.4 Hz, 2H), 6.97 (d, J = 8.0 Hz, 2H), 3.57 (s, 3H), 3.37 (s, 2H), 2.80-2.78 (m, 1H), 2.64- 2.61 (m, 1H), 2.10-1.99 (m, 5H), 1.83-1.72 (m, 14H), 1.63-1.62 (m, 1H), 1.47-1.40 (m, 2H). LC- MS: m/z 493.1 (M + H).sup.+ 252 VI.43 V.3 & Int-I [00255] .sup.1H NMR (400 MHz, DMSO-d6) δ 8.04 (s, 1H), 7.94 (d, J = 1.6 Hz, 1H), 7.77 (dd, J.sub.1 = 1.2 Hz, J.sub.2 = 7.6 Hz, 1H), 7.68-7.64 (m, 2H), 7.48 (d, J = 1.6 Hz, 1H), 7.43- 7.35 (m, 2H), 7.30 (d, J = 2.4 Hz, 1H), 7.18 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 8.4 Hz, 1H), 3.55 (s, 3H), 3.31 (s, 3H), 2.04 (s, 3H), 1.82 (s, 6H). LC-MS: m/z 503.1 (M + H).sup.+ 276, 293 VI.44 Int-II [00256] .sup.1H NMR (400 MHz, DMSO-d6) δ 9.23 (s, 1H), 8.69 (s, 1H), 7.88 (dd, J.sub.1 = 1.4 Hz, J.sub.2 = 7.8 Hz, 1H), 7.73 (d, J = 8.8 Hz, 2H), 7.41-7.37 (m, 1H), 7.23-7.17 (m, 4H), 7.10 (d, J = 7.9 Hz, 1H), 7.02 (d, J = 8.8 Hz, 2H), 6.77-6.73 (m, 1H), 3.75 (s, 3H), 1.51 (s, 9H). 277 VI.45 Int-II & I.16 [00257] .sup.1H NMR (400 MHz, DMSO-d6) δ 9.18 (s, 1H), 8.24 (s, 1H), 7.87 (dd, J.sub.1 = 1.2 Hz, J.sub.2 = 7.6 Hz, 1H), 7.40-7.28 (m, 3H), 7.20-7.10 (m, 10H), 7.02 (d, J = 8.4 Hz, 1H), 6.71 (t, J = 7.6 Hz, 1H), 3.85 (s, 3H), 3.11-3.07 (m, 1H), 1.13 (d, J = 2.8 Hz, 6H). LC-MS: m/z 437.1 (M + H).sup.+ 287 VI.46 Int-II & I.17 [00258] .sup.1H NMR (400 MHz, DMSO-d6) δ 9.15 (s, 1H), 8.07 (s, 1H), 7.86 (dd, J.sub.1 = 1.2 Hz, J.sub.2 = 7.6 Hz, 1H), 7.37-7.33 (m, 1H), 7.15-7.06 (m, 3H), 7.04-6.98 (m, 2H), 6.72- 6.68 (m, 1H), 3.85 (s, 3H), 3.40 (s, 3H), 2.36- 2.32 (m, 5H), 1.43-1.30 (m, 5H), 1.29-1.21 (m, 5H), 0.84 (t, J = 7.2 Hz, 6H). LC-MS: m/z 460.1 (M + H).sup.+ 291 VI.47 IV.3 & I.1 [00259] .sup.1H NMR (400 MHz, DMSO-d6) δ 8.49 (s, 1H), 7.87 (d, J = 7.2 Hz, 1H), 7.7-7.65 (m, 3H), 7.32-7.28 (m, 3H), 7.17- 7.13 (m, 4H), 3.94 (s, 3H), 3.8 (s, 3H), 2.06 (s, 3H), 1.83 (s, 6H), 1.74 (s, 6H). LC-MS: m/z 492.1 (M + H).sup.+ 292 VI.48 Int-II & I.19 [00260] .sup.1H NMR (400 MHz, DMSO-d6) δ 9.16 (s, 1H), 8.11 (s, 1H), 7.86 (dd, J.sub.1 = 1.5 Hz, J.sub.2 = 7.8 Hz, 1H), 7.33 (t, J = 1.5 Hz, 1H), 7.15-7.07 (m, 8H), 7.02-6.98 (m, 3H), 6.72-6.65 (m, 4H), 3.85 (s, 3H), 3.57 (t, J = 7.3 Hz, 2H), 1.58-1.51 (m, 2H), 1.36-1.30 (m, 2H), 0.88 (t, J = 7.3 Hz, 3H). LC-MS: m/z 466.1 (M + H).sup.+ 295 VI.49 Int-II & I.2 [00261] .sup.1H NMR (400 MHz, DMSO-d6) δ 9.14 (s, 1H), 8.02 (s, 1H), 7.86 (dd, J.sub.1 = 1.6 Hz, J.sub.2 = 8.0 Hz, 1H), 7.35 (t, J = 8.4 Hz, 1H), 7.21 (d, J = 8.8 Hz, 2H), 7.12-7.04 (m, 4H), 7.01-7.69 (m, 3H), 6.69 (t, J = 7.2 Hz, 1H), 3.85 (s, 3H), 2.13-2.12 (m, 1H), 1.66 (s, 2H), 1.50-1.32 (m, 8H), 1.17 (s, 2H), 0.85 (s, 6H). LC-MS: m/z 481.0 (M + H).sup.+ 309 VI.50 V.10 & I.21 [00262] .sup.1H NMR (400 MHz, DMSO-d6) δ 7.8 (d, J = 7.6 Hz, 1H), 7.71- 7.61 (m, 1H), 7.44-7.35 (m, 6H), 7.28 (d, J = 8.4 Hz, 2H), 6.50 (d, J = 8.4 Hz, 2H), 3.56 (s, 3H), 3.23 (s, 3H), 2.05 (s, 3H), 1.85 (s, 6H), 1.73 (s, 6H). LC-MS: m/z 476.1 (M + H).sup.+ 317 VI.51 V.6 & I.1 [00263] .sup.1H NMR (400 MHz, DMSO-d6) δ 8.49 (s, 1H), 7.84 (d, J = 7.6 Hz, 1H), 7.78-7.71 (m, 3H), 7.35-7.29 (m, 3H), 7.19- 7.13 (m, 4H), 3.91 (s, 3H), 3.89 (s, 3H), 2.06 (s, 3H), 1.86 (s, 6H), 1.74 (s, 6H). LC-MS: m/z 492.3 (M + H).sup.+ 318 VI.52 V.10 & I.22 [00264] .sup.1H NMR (400 MHz, DMSO-d6) δ 7.50-7.46 (m, 2H), 7.27 (d, J = 8.8 Hz, 2H), 7.19-7.17 (m, 1H), 7.08 (t, J = 7.6 Hz, 1H), 6.80 (d, J = 8.8 Hz, 2H), 6.64 (d, J = 8.8 Hz, 2H), 6.37 (d, J = 8.8 Hz, 2H), 5.09-5.06 (m, 1H), 4.23-4.20 (m, 2H), 3.64- 3.61 (m, 2H), 3.45 (s, 3H), 3.15 (s, 3H), 2.04 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 523.3 (M + H).sup.+ 323 VI.53 Int-II & I.26 [00265] .sup.1H NMR (400 MHz, DMSO-d6) δ 9.11 (s, 1H), 7.86-7.83 (m, 2H), 7.34 (t, J = 7.6 Hz, 1H), 7.07 (d, J = 8.4 Hz, 2H), 7.02 (d, J = 8.8 Hz, 2H), 6.96-6.92 (m, 3H), 6.85 (d, J = 8.8 Hz, 2H), 6.68 (t, J = 7.2 Hz, 1H), 3.85 (s, 3H), 3.48 (s, 2H), 1.99 (s, 3H), 1.74-1.63 (m, 13H). LC-MS: m/z 483.3 (M + H).sup.+ 327 VI.54 II.23 & I.16 [00266] .sup.1H NMR (400 MHz, DMSO-d6) δ 9.18 (s, 1H), 8.04 (s, 1H), 7.72- 7.67 (m, 3H), 7.37 (t, J = 6.4 Hz, 2H), 7.29 (t, J = 6.4 Hz, 1H), 7.18 (t, J = 6.8 Hz, 1H), 7.11- 6.97 (m, 8H), 4.34-4.29 (m, 2H), 3.13-3.08 (m, 1H), 1.34 (t, J = 7.2 Hz, 3H), 1.12 (d, J = 6.8 Hz, 6H). LC-MS: m/z 452.3 (M + H).sup.+ 328 VI.55 IV.5 & I.1 [00267] .sup.1H NMR (400 MHz, DMSO-d6) δ 6 8.44 (s, 1H), 7.93-7.91 (m, 1H), 7.72-7.67 (m, 1H), 7.45 (t, J = 2.0 Hz, 1H), 7.4 (t, J = 7.6 Hz, 1H), 7.33 (t, J = 8.0 Hz, 1H), 7.28- 7.27 (m, 2H), 7.23-7.17 (m, 2H), 7.12-7.1 (m, 2H), 3.94 (s, 3H), 3.78 (s, 3H), 2.08 (s, 3H), 1.84 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 492.3 (M + H).sup.+ 337 VI.56 V.10 & I.27 [00268] LC-MS: m/z 536.3 (M + H).sup.+ 340 VI.57 V.8 & I.1 [00269] .sup.1H NMR (400 MHz, DMSO-d6) δ 8.23 (bs, 1H), 7.70-7.59 (m, 2H), 7.47 (d, J = 7.2 Hz, 1H), 7.4-7.3 (m, 1H), 7.23 (d, J = 8.4 Hz, 2H), 6.99 (d, J = 8.0 Hz, 4H), 6.72 (bs, 2H), 3.73 (s, 3H), 3.28 (s, 3H), 2.04 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 495.3 (M + H).sup.+ 349 VI.58 Int-IV & I.4 [00270] .sup.1H NMR (400 MHz, DMSO-d6) δ 11.52 (s, 1H), 8.64 (d, J = 8.3 Hz, 1H), 8.24 (s, 1H), 8.02 (d, J = 8.4 Hz, 1H), 7.80 (d, J = 8.8 Hz, 2H), 7.64- 7.62 (m, 1H), 7.60 (s, 1H), 7.38-7.37 (m, 2H), 7.21-7.19 (m, 1H), 6.95 (d, J = 8.3 Hz, 2H), 3.91 (s, 3H), 2.07 (s, 3H), 1.88 (s, 6H), 1.74 (s, 6H). LC-MS: m/z 561.2 (M + H).sup.2+ 350 VI.59 Int-IV & Int-I [00271] .sup.1H NMR (400 MHz, DMSO-d6) δ 11.54 (s, 1H), 8.65-8.63 (dd, J.sub.1 = 1.2 Hz, J.sub.2 = 8.4 Hz, 1H), 8.35 (s, 1H), 8.01 (d, J = 1.6 Hz, 1H), 7.81 (d, J = 8.8 Hz, 2H), 7.69- 7.64 (m, 1H), 7.45 (d, J = 2.0 Hz, 1H), 7.39 (d, J = 8.4 Hz, 1H), 7.34 (d, J = 2.0 Hz, 1H), 7.22- 7.18 (dd, J.sub.1 = 1.2 Hz, J.sub.2 = 8.4 Hz, 1H), 6.99 (d, J = 8.8 Hz, 2H), 3.91 (s, 3H), 2.07 (s, 3H), 1.99 (s, 6H), 1.74 (s, 6H). LC-MS: m/z 515.1 (M + H).sup.2+ 361 VI.60 Int-IV & I.30 [00272] .sup.1H NMR (400 MHz, DMSO-d6) δ 11.55 (s, 1H), 8.56 (d, J = 8.3 Hz, 1H), 8.02 (d, J = 7.8 Hz, 1H), 7.97 (d, J = 8.8 Hz, 2H), 7.68 (t, J = 7.0 Hz, 1H), 7.44 (d, J = 8.8 Hz, 2H), 7.24 (t, J = 7.0 Hz, 1H), 7.13 (d, J = 8.3 Hz, 2H), 7.07 (d, J = 8.8 Hz, 2H), 3.89 (s, 3H), 2.07 (s, 3H), 1.89 (s, 6H), 1.75 (s, 6H). LC-MS: m/z 482.3 (M + H).sup.1+ 385 VI.61 Int-II.10 & I.19 [00273] LC-MS: m/z 467.3 (M + H).sup.+ 386 VI.62 II.10 [00274] .sup.1H NMR (400 MHz, DMSO-d6) δ 10.01 (s, 1H), 8.63 (s, 1H), 8.39 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 4.8 Hz, 1H), 8.24 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 27.6 Hz, 1H), 7.72 (d, J = 8.4 Hz, 2H), 7.65 (d, J = 8.8 Hz, 2H), 7.16 (d, J = 8.8 Hz, 2H), 6.98 (d, J = 8.8 Hz, 2H), 6.86 (dd, J.sub.1 = 4.8 Hz, J.sub.2 = 7.6 Hz, 1H), 3.91 (s, 3H), 1.52 (s, 9H). LC-MS: m/z 420.1 (M + H).sup.+ 388 VI.63 Int-II & I.28 [00275] .sup.1H NMR (400 MHz, DMSO-d6) δ 9.15 (s, 1H), 7.86 (dd, J.sub.1 = 1.2 Hz, J.sub.2 = 7.6 Hz, 1H), 7.55 (s, 1H), 7.37-7.26 (m, 1H), 7.25-7.19 (m, 3H), 7.11 (d, J = 8.4 Hz, 2H), 7.04 (d, J = 2.8 Hz, 1H), 7.0-6.96 (m, 3H), 6.91- 6.85 (m, 4H), 6.70 (t, J = 6.8 Hz, 1H), 3.63 (t, J = 7.2 Hz, 3H), 1.56-1.5 (m, 2H), 1.36-1.3 (m, 2H), 0.88 (t, J = 7.2 Hz, 3H). LC-MS: m/z 500.2 (M + H).sup.+ 389 VI.64 II.10 & I.28 [00276] .sup.1H NMR (400 MHz, DMSO-d6) δ 9.91 (s, 1H), 8.35 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 4.8 Hz, 1H), 8.22 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 7.6 Hz, 1H), 7.53 (d, J = 8.8 Hz, 2H), 7.44 (s, 1H), 7.24-7.20 (m, 2H), 7.16 (d, J = 8.8 Hz, 1H), 7.05 (d, J = 2.4 Hz, 1H), 6.99 (d, J = 8.8 Hz, 2H), 3.89 (s, 3H), 3.61 (t, J = 7.2 Hz, 2H), 1.56-1.52 (m, 2H), 1.36-1.30 (m, 2H), 0.88 (t, J = 7.2 Hz, 3H). LC-MS: m/z 501.2 (M + H).sup.+ 127 VI. 65 II.2 & Int-I [00277] .sup.1H NMR (400 MHz, DMSO-d6) δ 10.16 (s, 1H), 8.41 (s, 1H), 8.34 (d, J = 8.8 Hz, 1H), 8.05 (d, J = 5.6 Hz, 1H), 7.90 (d, J = 8.0 Hz, 1H), 7.70 (d, J = 8.8 Hz, 1H), 7.43- 7.39 (m, 2H), 7.32-07.30 (m, 1H), 7.08 (t, J = 8.0 Hz, 1H), 6.32 (d, J = 6.0 Hz, 1H), 3.83 (s, 3H), 2.07 (s, 3H), 1.88 (s, 6H), 1.74 (s, 6H).

Intermediate-VII

[0559] ##STR00278##

Step-d: Synthesis of 4-((3R,5R)-adamantan-1-yl)-2-chloro-N-(4-nitrophenyl) aniline (Intermediate-VII)

[0560] A solution of Intermediate-I (8.5 g, 32.5 mmol, 1 eq.) and 4-bromonitrobenzene (6.57 g, 32.5 mmol, 1 eq.) in toluene (100 mL) was de-gassed by bubbling Nitrogen gas for 5 minutes. Cesium carbonate (16 g, 48.9 mmol, 1.5 eq.) was added followed by Palladium acetate (0.72 g, 3.25 mmol, 0.1 eq.) and XPhos (2.32 g, 4.88 mmol, 0.15 eq.) and de-gassed again for 5 min. Reaction mixture was heated at 110° C. under stirring for 16 h. Reaction mixture was cooled to RT, diluted with ethyl acetate and filtered through celite. The organic layer was adsorbed over silica and purified by flash column chromatography. Desired product was eluted in 5 to 10% ethyl acetate in hexanes. Concentrated in vacuo to afford dark yellow oil (7 g, 57%).

[0561] .sup.1H NMR (400 MHz, DMSO-d6) δ 8.98 (s, 1H), 8.09-8.07 (m, 2H), 7.44 (s, 1H), 7.38 (s, 2H), 6.83-6.79 (m, 2H), 2.06 (s, 3H), 1.88 (s, 6H), 1.74 (s, 6H); LC-MS: m/z 383.2 (M+H).sup.+

[0562] The below intermediates were prepared by a procedure similar to Intermediate-VII using appropriate reactants and reagents employing suitable Pd catalysts and ligands and in presence of suitable solvents and appropriate reaction conditions.

TABLE-US-00012 Intermediate CP No. Structure Analytical data 58, 59, 60, 61, 266 VII.1 [00279] LC-MS: m/z 415.05 (M − H).sup.−. 62 VII.2 [00280] n/a 66, 128, 129, 211 VII.3 [00281] LC-MS: m/z 449.1 (M − H).sup.− 67, 275 VII.4 [00282] .sup.1H NMR (400 MHz, DMSO- d6) δ 9.06 (s, 1H), 8.15 (d, J = 2.8 Hz, 1H), 7.66 (dd, J.sub.1 = 2.8 Hz, J.sub.2 = 8.8 Hz, 1H), 7.49 (d, J = 8.8 Hz, 2H), 7.23 (d, J = 8.8 Hz, 2H), 6.75 (d, J = 8.8 Hz, 1H), 2.03 (s, 3H), 1.82 (s, 6H), 1.71 (s, 6H). 132, 133 VII.5 [00283] .sup.1H NMR (400 MHz, DMSO- d6) δ 9.00 (s, 1H), 8.10 (d, J = 9.2 Hz, 2H), 7.55-7.50 (m, 2H), 7.37-7.28 (m, 5H), 6.96 (d, J = 9.2 Hz, 2H), 2.28 (s, 3H). LC-MS: m/z 339.5 (M + H).sup.+ 106, 145 VII.6 [00284] .sup.1H NMR (400 MHz, DMSO- d6) δ 8.34 (s, 1H), 7.76 (d, J = 8.8 Hz, 2H), 7.43 (s, 1H), 7.34-7.33 (m, 2H), 6.87 (d, J = 8.8 Hz, 2H), 4.24 (m, 2H), 2.04 (s, 3H), 1.86 (s, 6H), 1.73 (s, 6H), 1.28 (t, J = 6.8 Hz, 3H). LC-MS: m/z 410.1 (M + H).sup.+ 169 VII.7 [00285] LC-MS: m/z 426.2 (M + H).sup.+ 191 VII.8 [00286] .sup.1H NMR (400 MHz, DMSO- d6) δ 9.25 (s, 1H), 8.09 (d, J = 9.3 Hz, 2H), 7.32 (t, J = 7.8 Hz, 1H), 7.17 (s, 1H), 7.12- 7.07 (m, 2H), 7.03 (d, J = 9.3 Hz, 2H), 2.06 (s, 3H), 1.87 (s, 6H), 1.74 (s, 6H). LC-MS: m/z 349.1 (M + H).sup.+ 204, 261 VII.9 [00287] LC-MS: m/z 383.0 (M + H).sup.+ 249 VII.10 [00288] LC-MS: m/z 397.0 (M + H).sup.+ 271 VII.11 [00289] .sup.1H NMR (400 MHz, DMSO- d6) δ 8.60 (s, 1H), 8.32 (d, J = 2.8 Hz, 1H), 8.19 (dd, J.sub.1 = 2.8 Hz, J.sub.2 = 9.2 Hz, 1H), 7.44 (d, J = 8.0 Hz, 2H), 7.24 (d, J = 8.4 Hz, 2H), 6.98 (d, J = 9.2 Hz, 1H), 2.07 (s, 3H), 1.89 (s, 6H), 1.75 (s, 6H). LC- MS: m/z 415.05 (M − H).sup.− 272 VII.12 [00290] .sup.1H NMR (400 MHz, DMSO- d6) δ 9.86 (s, 1H), 8.18 (d, J = 9.3 Hz, 2H), 8.04 (dd, J.sub.1 = 1.4 Hz, J.sub.2 = 8.3 Hz, 1H), 7.53-7.45 (m, 2H), 7.23 (s, 2H), 6.96 (t, J = 6.9 Hz, 1H), 3.93 (s, 3H). 289, 311, 379 VII.13 [00291] .sup.1H NMR (400 MHz, DMSO- d6) δ 8.05 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 7.4 Hz, 2H), 7.48 (d, J = 8.4 Hz, 2H), 7.25 (d, J = 8.3 Hz, 2H), 6.74 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 7.4 Hz, 2H), 3.36 (s, 3H), 2.80 (s, 3H), 1.89 (s, 6H), 1.75 (s, 6H). LC-MS: m/z 363.1 (M + H).sup.+ 297, 300 VII.14 [00292] .sup.1H NMR (400 MHz, DMSO- d6) δ 8.75 (s, 1H), 7.58 (t, J = 7.6 Hz, 1H), 7.33-7.27 (m, 3H), 6.83 (d, J = 8.4 Hz, 1H), 6.54 (d, J = 8.8 Hz, 2H), 4.76 (s, 2H), 4.33-4.26 (m, 2H), 1.32 (t, J = 7.6 Hz, 3H). LC-MS: m/z 258.1 (M + H).sup.+ 298, 299 VII.15 [00293] .sup.1H NMR (400 MHz, DMSO- d6) δ 10.58 (s, 1H), 8.55 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 4.8 Hz, 1H), 8.35 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 7.6 Hz, 1H), 8.24-8.20 (m, 2H), 8.05-8.01 (m, 2H), 7.10 (dd, J.sub.1 = 4.4 Hz, J.sub.2 = 7.6 Hz, 1H), 3.93 (s, 3H). LC-MS: m/z 274.10 (M + H).sup.+ 319 VII.16 [00294] .sup.1H NMR (400 MHz, DMSO- d6) δ 9.22 (s, 1H), 8.06 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 7.6 Hz, 2H), 7.36 (d, J = 8.4 Hz, 2H), 7.17 (d, J = 8.8 Hz, 2H), 7.00 (d, J = 9.2 Hz, 2H), 2.14 (m, 1H), 1.69 (s, 2H), 1.53-1.36 (m, 8H), 1.19 (s, 2H), 0.86 (s, 6H). LC-MS: m/z 377.1 (M + H).sup.+ 320 VII.17 [00295] .sup.1H NMR (400 MHz, DMSO- d6) δ 9.40 (s, 1H), 8.07 (d, J = 9.3 Hz, 2H), 7.24 (m, 2H), 7.18 (d, J = 8.8 Hz, 2H), 7.00 (m, 4H), 6.96-6.91 (m, 3H), 3.60 (m, 2H), 1.60 (m, 2H), 1.40-1.35 (m, 2H), 0.88 (t, J = 7.4 Hz, 3H). 338 VII.18 [00296] .sup.1H NMR (400 MHz, DMSO- d6) δ 9.48 (s, 1H), 8.12 (d, J = 9.2 Hz, 2H), 7.80 (d, J = 8.8 Hz, 2H), 7.46 (s, 1H), 7.24 (d, J = 8.4 Hz, 2H), 7.15 (d, J = 8.8 Hz, 2H), 2.06 (s, 9H), 1.65 (s, 6H). LC-MS: m/z 392.1 (M + H).sup.+ 352 VII.19 [00297] LC-MS: m/z 349.1 (M + H).sup.+ 378 VII.20 [00298] LC-MS: m/z 349.2 (M + H).sup.+ 271 VII.21 [00299] LC-MS: m/z 431.15 (M + H).sup.+ 521, 541, 605, 606, 607, 608, VII.22 [00300] LC-MS: m/z 283.1 (M + H)+ 613, 648 522, 536, 558 VII.23 [00301] LC-MS: m/z 297.2 (M + H)+ 528 VII.24 [00302] LC-MS: m/z 339.0 (M − H)− 535 VII.25 [00303] 1H NMR (400 MHz, DMSO- d6): δ 9.36 (s, 1H), 8.10 (d, J = 9.2 Hz, 2H), 7.42 (d, J = 8.8 Hz, 2H), 7.26 (d, J = 8.8 Hz, 2H), 7.08 (d, J = 9.2 Hz, 2H). 537 VII.26 [00304] LC-MS: m/z 367.2 (M + H)+ 538 VII.27 [00305] 1H NMR (400 MHz, DMSO- d6) δ 9.22 (s, 1H), 8.06 (dd, J1 = 2 Hz & J2 = 7.6 Hz, 2H), 7.22 (d, J = 8.4 Hz, 2H), 7.15 (dd, J1 = 1.6 Hz & J2 = 6.4 Hz, 2H), 6.99 (dd, J1 = 2 Hz & J2 = 7.2 Hz, 2H), 271-2.69 (m, 1H), 2.33 (brs, 1H), 2.27 (brs, 1H), 1.73-1.70 (m, 1H), 1.55- 1.46 (m, 4H), 1.35-1.29 (m, 2H), 1.16-1.14 (m, 1H). LC- MS: m/z 309.1 (M + H)+. 542 VII.28 [00306] LC-MS: m/z 283.0 (M + H)+ 545 VII.29 [00307] LC-MS: m/z 245.1 (M + H)+ 547 VII.30 [00308] 1H NMR (400 MHz, DMSO- d6): δ 9.08 (s, 1H), 8.03 (d, J = 9.2 Hz, 2H), 7.12 (d, J = 8.8 Hz, 2H), 6.98 (d, J = 8.8 Hz, 2H), 6.87 (d, J = 9.2 Hz, 2H), 3.75-3.73 (m, 4H), 3.10-3.08 (m, 4H). LC-MS: m/z 300.1 (M + H)+. 548 VII.31 [00309] 1H NMR (400 MHz, DMSO- d6): δ 9.41 (s, 1H), 8.11 (d, J = 9.2 Hz, 2H), 7.38-7.32 (m, 4H), 7.10 (d, J = 9.2 Hz, 2H). LC-MS: m/z 297.1 (M − H)− 549 VII.32 [00310] LC-MS: m/z 315.2 (M + H)+ 551 VII.33 [00311] LC-MS: m/z 363.1 (M + H)+ 553 VII.34 [00312] 1H NMR (400 MHz, DMSO- d6): δ 9.17 (s, 1H), 8.06 (d, J = 9.2 Hz, 2H), 7.21 (d, J = 8.8 Hz, 2H), 7.10 (d, J = 8.8 Hz, 2H), 6.92 (d, J = 8.8 Hz, 2H), 4.75 (q, J = 9.2 Hz, 2H). 554, 567 VII.35 [00313] LC-MS: m/z 241.2 (M − H)− 555, 556, 574, 583, 584, 552, VII.36 [00314] LC-MS: m/z 312.2 (M + H)+ 557, 582, 593 560, 579, 580, 614, 619, 620, 621, 625, VII.37 [00315] LC-MS: m/z 311.1 (M + H)+ 627, Also for CP compounds 630, 631, 628, 632, 633, 634, 635, 636, 637, 640, 629 653, 656, 657, 678, 679 563 VII.38 [00316] 1H NMR (400 MHz, DMSO- d6): δ 9.43 (s, 1H), 8.03 (d, J = 10 Hz, 1H), 7.64 (d, J = 8.8 Hz, 2H), 7.35 (d, J = 8.4 Hz, 2H), 7.08-7.06 (m, 2H), 2.53 (s, 3H). 565 VII.39 [00317] LC-MS: m/z 327.0 (M + H)+ 568 VII.40 [00318] LC-MS: m/z 328.95 (M − H)− 571 VII.41 [00319] LC-MS: m/z 355.1 (M + H)+ 572 VII.42 [00320] LC-MS: m/z 298.95 (M − H)−. 573 VII.43 [00321] LC-MS: m/z 357.0 (M − H)−. 576 VII.44 [00322] LC-MS: m/z 284.0 (M + H)+ 577 VII.45 [00323] LC-MS: m/z 323.3 (M + H)+ 578 VII.46 [00324] LC-MS: m/z 298.2 (M + H)+ 581 VII.47 [00325] LC-MS: m/z 296.0 (M + 2)+ 585 VII.48 [00326] LC-MS: m/z 327.1 (M + H)+ 588 VII.49 [00327] LC-MS: m/z 289.95 (M + H) 589 VII.50 [00328] LC-MS: m/z 315.1 (M − H)− 590 VII.51 [00329] LC-MS: m/z 311.1 (M − H)− 592 VII.52 [00330] LC-MS: m/z 316.9 (M + H)+ 594 VII.53 [00331] LC-MS: m/z 332.1 (M − H) − 595 VII.54 [00332] LC-MS: m/z 342.0 (M + H) + 596 VII.55 [00333] LC-MS: m/z 335.0 (M + H) + 597 VII.56 [00334] LC-MS: m/z 304.2 (M + H)+ 602 VII.57 [00335] LC-MS: m/z 320.0 (M + H)+ 609, 652, 673 VII.58 [00336] LC-MS: m/z 312.2 (M + H)+ 612 VII.59 [00337] LC-MS: m/z 283.0 (M + H)+ 617 VII.60 [00338] LC-MS: m/z 315.0 (M − H)− 618 VII.61 [00339] Proceeded with crude/TLC reference 622 VII.62 [00340] LC-MS: m/z 315.0 (M + H)+ 624 VII.63 [00341] LC-MS: m/z 287.0 (M + H)+ 626 VII.64 [00342] LC-MS: m/z 337.2 (M + H)+ 641, 661, 662 VII.65 [00343] LC-MS: m/z 363.1 (M1H)− 660, 675, 676 VII.66 [00344] LC-MS: m/z 397.1 (M − H)− 598, 643, 654, 655 VII.67 [00345] LC-MS: m/z 333.1 (M + H)+ 646 VII.68 [00346] LC-MS: m/z 327.1 (M + H)+ 647 VII.69 [00347] LC-MS: m/z 313.1 (M + H)+ 659 VII.70 [00348] LC-MS: m/z 332.1 (M + H)+ 663 VII.71 [00349] LC-MS: m/z 338.2 (M + H)+ 671, 680, 681 VII.72 [00350] LC-MS: m/z 345.1 (M + H)+ 682, 677 VII.73 [00351] LC-MS: m/z 331.1 (M + H)+

[0563] The below intermediates were prepared by a procedure similar to Intermediate-V using appropriate reactants and reagents employing suitable Pd catalysts and ligands and in presence of suitable solvents and appropriate reaction conditions.

TABLE-US-00013 Intermediate CP No. Reactant Structure Analytical data 249 VII.74 VII [00352] LC-MS: m/z 397.0 (M + H).sup.+ 289, 311, 379 VII.75 VII.17 [00353] .sup.1H NMR (400 MHz, DMSO-d6) δ 8.05 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 7.4 Hz, 2H), 7.48 (d, J = 8.4 Hz, 2H), 7.25 (d, J = 8.3 Hz, 2H), 6.74 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 7.4 Hz, 2H), 3.36 (s, 3H), 2.80 (s, 3H), 1.89 (s, 6H), Also for CP compounds 453, 472, 1.75 (s, 6H). LC-MS: 473, 525, 526 m/z 363.1 (M + H).sup.+ 271 VII.76 VII.10 [00354] LC-MS: m/z 431.15 (M + H).sup.+ 521, 541, 605, 606, 607, 608, VII.77 VII.19 [00355] LC-MS: m/z 297.1 (M + H).sup.+. 613, 648 522, 536, 558 VII.78 VII.20 [00356] LC-MS: m/z 311.1 (M + H).sup.+ 528 VII.79 VII.21 [00357] LC-MS: m/z 355.1 (M + H).sup.+ 535 VII.80 VII.22 [00358] .sup.1H NMR (400 MHz, DMSO-d.sub.6): δ 8.06 (d, J = 9.2 Hz, 2H), 7.55 (d, J = 8.8 Hz, 2H), 7.36 (d, J = 8.4 Hz, 2H), 6.81 (d, J = 9.2 Hz, 2H), 3.37 (s, 3H). 537 VII.81 VII.23 [00359] LC-MS: m/z 381.2 (M + H).sup.+ 538 VII.82 VII.24 [00360] .sup.1H NMR (400 MHz, DMSO-d.sub.6): δ 8.03 (dd, J.sub.1 = 2.4 Hz & J.sub.2 = 7.6 Hz, 2H), 7.33 (d, J = 8.4 Hz, 2H), 7.23-7.20 (m, 2H), 6.72 (dd, J.sub.1 = 2 Hz & J.sub.2 = 7.6 Hz, 2H), 3.35 (s, 3H), 2.79-2.75 (m, 1H), 2.34-2.31 (m, 2H), 1.76-1.73 (m, 1H), 1.56-1.50 (m, 4H), 1.36-1.16 (m, 3H). LC-MS: m/z 323.2 (M + H).sup.+ 542 VII.83 VII.25 [00361] LC-MS: m/z 297.1 (M + H).sup.+ 545 VII.84 VII.26 [00362] LC-MS: m/z 259.1 (M + H).sup.+ 547 VII.85 VII.27 [00363] .sup.1H NMR (400 MHz, DMSO-d.sub.6): δ 8.02 (d, J = 9.6 Hz, 2H), 7.16 (d, J = 8.8 Hz, 2H, 7.04 (d, J = 8.8 Hz, 2H), 6.67 (d, J = 9.6 Hz, 2H), 3.76-3.74 (m, 4H), 3.32 (s, 3H), 3.16-3.13 (m, 4H). LC-MS: m/z 314.2 (M + H).sup.+ 548 VII.86 VII.28 [00364] .sup.1H NMR (400 MHz, DMSO-d.sub.6): δ 8.07 (d, J = 9.2 Hz, 2H), 7.48- 7.45 (m, 4H), 6.81 (d, J = 9.2 Hz, 2H), 3.39 (s, 3H). LC-MS: m/z 313.1 (M + H).sup.+ 549 VII.87 VII.29 [00365] LC-MS: m/z 329.2 (M + H).sup.+. 551 VII.88 VII.30 [00366] LC-MS: m/z 377.3 (M + H).sup.+. 552 VII.89 VII.33 [00367] LC-MS: m/z 345.1 (M + H).sup.+. 553 VII.90 VII.31 [00368] LC-MS: m/z 327.1 (M + H).sup.+. 554, 567 VII.91 VII.32 [00369] LC-MS: m/z 257.2 (M + H).sup.+. 555 VII.92 VII.33 [00370] LC-MS: m/z 312.2 (M + H).sup.+. 556 VII.93 VII.33 [00371] LC-MS: m/z 241.2 (M − H).sup.− 557 VII.94 VII.33 [00372] LC-MS: m/z 312.2 (M + H).sup.+ 560, 579, 580, 614, 619, 620, 621, 625, 627 VII.95 VII.34 [00373] LC-MS: m/z 325.2 (M + H).sup.+ Also for CP compounds 628, 629, 630, 631, 632, 633, 634, 635, 636, 637, 640, 653, 656, 657, 678, 679 563 VII.96 VII.35 [00374] LC-MS: m/z 311.05 (M + H).sup.+ 565 VII.97 VII.36 [00375] LC-MS: m/z 341.0 (M + H).sup.+ 568 VII.98 VII.37 [00376] .sup.1H NMR (400 MHz, DMSO-d.sub.6): δ 7.98- 7.94 (m, 1H), 7.31 (d, J = 8.8 Hz, 2H), 7.19 (d, J = 8.8 Hz, 2H), 6.57 (dd, J.sub.1 = 2.0 Hz & J.sub.2 = 14.8 Hz, 1H), 6.42 (dd, J.sub.1 = 2.0 Hz & J.sub.2 = 9.2 Hz, 1H), 4.82 (q, J = 8.8 Hz, 2H), 3.34 (s, 3H). 571 VII.99 VII.38 [00377] LC-MS: m/z 369.1 (M + H).sup.+ 572 VII.100 VII.39 [00378] LC-MS: m/z 315.1 (M + H).sup.+ 573 VII.101 VII.40 [00379] LC-MS: m/z 357.0 (M − H).sup.− 574, 583, 584 VII.102 VII.33 [00380] LC-MS: m/z 284.0 (M + H).sup.+ 576 VII.103 VII.41 [00381] LC-MS: m/z 298 (M + H).sup.+ 577 VII.104 VII.42 [00382] LC-MS: m/z 337.2.0 (M + H).sup.+ 578 VII.105 VII.43 [00383] LC-MS: m/z 312.2 (M + H).sup.+ 581 VII.106 VII.44 [00384] LC-MS: m/z 310.1 (M + H).sup.+ 582 VII.107 VII.33 [00385] LC-MS: m/z 324.2 (M + H).sup.+ 585 VII.108 VII.45 [00386] LC-MS: 342.1 m/z (M + H).sup.+ 588 VII.109 VII.46 [00387] LC-MS: m/z 304.1 (M + H).sup.+ 589 VII.110 VII.47 [00388] LC-MS: m/z 331.1 (M − H).sup.− 590 VII.111 VII.48 [00389] LC-MS: m/z 327.1 (M − H).sup.− 592 VII.112 VII.49 [00390] LC-MS: m/z 331.0 (M − H).sup.− 593 VII.113 VII.33 [00391] LC-MS: m/z 337.1 (M + H).sup.+ 594 VII.114 VII.50 [00392] LC-MS: m/z 346.0 (M + H).sup.+ 595 VII.115 VII.51 [00393] LC-MS: m/z 356.1 (M − H).sup.− 597 VII.116 VII.53 [00394] LC-MS: m/z 318.1 (M + H).sup.+ 602 VII.117 VII.54 [00395] LC-MS: m/z 332.0 (M + H).sup.+ 603 VII.118 VII.52 [00396] LC-MS: m/z 377.1 (M + H).sup.+ 609, 652, 673 VII.119 VII.55 [00397] LC-MS: m/z 326.2 (M + H).sup.+ 612 VII.120 VII.56 [00398] LC-MS: m/z 297.0 (M + H).sup.+ 617 VII.121 VII.57 [00399] LC-MS: m/z 331.0 (M + H).sup.+ 618 VII.122 VII.58 [00400] LC-MS: m/z 315.2 (M + H).sup.+ 622 VII.123 VII.59 [00401] LC-MS: m/z 329.0 (M + H).sup.+ 624 VII.124 VII.60 [00402] LC-MS: m/z 301.0 (M + H).sup.+ 626 VII.125 VII.61 [00403] LC-MS: m/z 351.1 (M + H).sup.+ 598, 643, 654, 655 VII.126 VII.64 [00404] LC-MS: m/z 345.1 (M + H).sup.+ 646 VII.127 VII.65 [00405] LC-MS: m/z 340.95 (M + H).sup.+ 647 VII.128 VII.66 [00406] LC-MS: m/z 326.95 (M + H).sup.+ 659 VII.129 VII.67 [00407] LC-MS: m/z 346.1 (M + H).sup.+ 663 VII.130 VII.68 [00408] LC-MS: m/z 352.2 (M + H).sup.+ 671, 681 VII.131 VII.69 [00409] LC-MS: m/z 359.1 (M + H).sup.+

Intermediate-VII

[0564] ##STR00410##

Step-a: Synthesis of N-(4-((3R,5R)-adamantan-1-yl)phenyl)-3-nitrobenzamide (Intermediate-VIII)

[0565] The title compound (1.6 g, 960) was synthesized from intermediate-I.1 (1 g, 4.4 mmol, 1 eq.) and 3-nitrobenzoyl chloride (0.82 g, 4.4 mmol, 1 eq.) using a procedure similar to Intermediate-IV. LC-MS: m/z 377.2 (M+H).sup.+

[0566] The below intermediates were prepared by a procedure similar to Intermediate-VII using appropriate reactants and reagents and in presence of suitable solvents and appropriate reaction conditions.

TABLE-US-00014 Intermediate CP No. Structure Analytical data  366, 367 VIII.1 [00411] .sup.1H NMR (400 MHz, DMSO-d6) δ 10.43 (s, 1H), 8.80 (s, 1H), 8.47-8.40 (m, 2H), 7.85 (t, J = 7.6 Hz, 1H), 7.51-7.49 (m, 2H), 7.41-7.39 (m, 1H), 2.08 (s, 3H), 1.89 (s, 6H), 1.75 (s, 6H). LC-MS: m/z 411.1 (M + H).sup.+ 373 VIII.2 [00412] LC-MS: m/z 411.05 (M + H).sup.+ 395 VIII.3 [00413] .sup.1H NMR (400 MHz, DMSO-d6) δ 10.53 (s, 1H), 8.79 (t, J = 2.0 Hz, 1H), 8.45-8.39 (m, 2H), 7.84 (t, J = 8.0 Hz, 1H), 7.72-7.69 (m, 2H), 7.25-7.21 (m, 2H), 7.06-7.03 (m, 2H), 6.91- 6.90 (m, 2H), 6.88-6.84 (m, 1H), 3.67 (t, J = 7.2 Hz, 2H), 1.59-1.53 (m, 2H), 1.36-1.29 (m, 2H), 0.88 (t, J = 7.2 Hz, 3H). LC-MS: m/z 390.2 (M + H).sup.+ 339 VIII.4 [00414] LC-MS: m/z 405.1 (M + H).sup.+ 586 VIII.5 [00415] LC-MS: m/z 309.1 (M − H)− 642 VIII.6 [00416] LC-MS: m/z 339.05 (M + H)+ 649 VIII.7 [00417] 1H NMR (400 MHz, DMSO-d6) δ 10.57 (s, 1H), 8.45 (s, 1H), 7.93 (d, J = 8.0 Hz, 1H), 7.71-7.68 (m, 1H), 7.58 (s, 1H), 7.54-7.44 (m, 3H), 3.86 (s, 3H), 2.38 (s, 3H).  665,  666,  669, 672 VIII.8 [00418] LC-MS: m/z 359.1 (M + H).sup.+

Intermediate-IX

[0567] ##STR00419##

Step-a: Synthesis of (3R,5R)-1-(3-chloro-4-(4-nitrophenoxy)phenyl)adamantane (Intermediate-IX)

[0568] A solution of 4-fluoronitrobenzene (0.6 mL, 5.7 mmol) and Intermediate-1.25 (1.5 g, 6.84 mmol, 1.2 eq.) in DMSO (10 mL) was added with potassium carbonate (1.57 g, 11.4 mmol, 2 eq.) and allowed to stir at RT overnight. Reaction mass was poured on to cold water and obtained solid was filtered and dried to afford title compound as off-white solid (2 g, 910%).

[0569] .sup.1H NMR (400 MHz, DMSO-d6) δ 8.26 (d, J=9.3 Hz, 2H), 7.58 (s, 1H), 7.47 (d, J=2.0 Hz, 1H), 7.32 (d, J=8.8 Hz, 1H), 7.1 (d, J=8.3 Hz, 2H), 2.07 (bs, 2H), 1.89 (s, 6H), 1.7 (s, 6H). LC-MS: m/z 382.0 (M−H).sup.−

[0570] The below intermediates were prepared by a procedure similar to Intermediate-IX using appropriate reactants and reagents and in presence of suitable solvents and appropriate reaction conditions.

TABLE-US-00015 Intermediate CP No. Reactant Structure Analytical data 270, 314  IX.1  I.30 [00420] .sup.1H NMR (400 MHz, DMSO-d6) δ 8.24 (d, J = 8.8 Hz, 2H), 7.47 (d, J = 8.8 Hz, 2H), 7.11 (m, 4H), 2.07 (s, 3H), 1.88 (s, 6H), 1.71 (s, 6H). 360  IX.2  I.32 [00421] .sup.1H NMR (400 MHz, DMSO-d6) δ 8.31 (d, J = 8.8 Hz, 2H), 7.57 1H), 7.44-7.36 (m, 4H), 7.26 (t, J = 7.3 Hz, 1H), 7.19 (t, J = 8.8 Hz, 3H), 2.99-2.95 (m, 1H), 1.17 (d, J = 6.8 Hz, 6H). 383, 384  529, 531, IX.3  I.31 [00422] .sup.1H NMR (400 MHz, DMSO-d6) δ 8.27-8.23 (m, 2H), 7.58 (d, J = 2.0 Hz, 1H), 7.45 (dd, J.sub.1 = 2.4 Hz, J.sub.2 = 8.8 Hz, 1H), 7.31 (d, J = 8.4 Hz, 1H), 7.09-7.03 (m, 2H), 2.17-2.14 (m, 1H), 1.72 (s, 2H), 1.55-1.36 (m, 8H), 1.20 (s, 2H), 0.87 (s, 6H). 534  IX.4  [00423] LC-MS: m/z 419.0 (M + H).sup.+ 540  IX.5  [00424] LC-MS: m/z 576.2 (M + H).sup.+. 543, 544  IX-6  [00425] .sup.1H NMR (400 MHz, DMSO-d6) δ 8.35-8.27 (m, 2H), 8.15 (s, 1H), 7.84 (d, J = 8.4 Hz, 2H), 7.24 (d, J = 9.2 Hz, 2H). 546, 550  IX.7  [00426] Proceeded with crude/TLC reference 561, 564  IX.8  [00427] .sup.1H NMR (400 MHz, DMSO- d.sub.6): δ 8.06 (d, J = 9.2 Hz, 1H), 7.56 (d, J = 1.6 Hz, 1H), 7.44-7.42 (m, 1H), 7.26 (d, J = 8.4 Hz, 1H), 7.04 (d, J = 2 Hz, 1H), 6.81- 6.78 (m, 1H), 2.52 (s, 3H), 2.15 (s, 1H), 1.72-1.19 (m, 12H), 0.86-0.84 (m, 6H). 566, 591  IX.9  [00428] LC-MS: m/z 368.0 (M + 2H).sup.+ 569, 570  IX.10 [00429] Proceeded with crude/TLC reference 575  IX.11 [00430] .sup.1H NMR (400 MHz, DMSO- d.sub.6): δ 8.29-8.26 (m, 2H), 7.93 (s, 1H), 7.69 (d, J = 8.4 Hz, 1H), 7.50 (d, J = 8.4 Hz, 1H), 7.24- 6.96 (m, 3H). 587  IX.12 [00431] LC-MS: m/z 338.85 (M + H).sup.+ 599  IX.13 [00432] LC-MS: m/z 361.3 (M + H).sup.+ 600  IX.14 [00433] LC-MS: m/z 334.05 (M+).sup.+ 601  IX.15 [00434] LC-MS: m/z 319.0 (M + H).sup.+ 615  IX.16 [00435] LC-MS: m/z 377.0 (M + H).sup.+ 616  IX.17 [00436] LC-MS: m/z 388.0 (M + H).sup.+

Intermediate-X

[0571] ##STR00437##

Step-a: Synthesis of (3r,5r,7r)-1-(3-chloro-4-methylphenyl)adamantane (Xa)

[0572] A solution of (3r,5r,7r)-1-(p-tolyl)adamantane (2 g, 8.8 mmol) in acetic acid was added with N-chlorosuccinimide in portions for a period of 30 minutes. Reaction mass was heated at 75° C. overnight. Reaction mass was poured on to cold water and obtained solid was filtered off and dried under vacuum. Title compound was obtained as white solid (2.2 g, 960%). .sup.1H NM/R (400 MHz, DMSO-d6) δ 7.31 (d, J=1.9 Hz, 1H), 7.26-7.22 (m, 2H), 2.27 (s, 3H), 2.04 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H).

Step-b: Synthesis of (3r,5r,7r)-1-(4-(bromomethyl)-3-chlorophenyl)adamantane (Xb)

[0573] A solution of compound Xa (1 g, 3.8 mmol) in carbon tetrachloride (40 mL) was added with Bromine (0.61 g, 3.8 mmol) drop wise and Benzoyl peroxide (catalytic). Reaction mass was heated to reflux overnight. Concentrated in vacuo and crude was purified by column chromatography to afford title product as off-white solid (0.5 g, 380%). .sup.1H NMR (400 MHz, DMSO-d6) δ 7.38 (d, J=8.0 Hz, 2H), 7.24 (m, 1H), 4.58 (s, 2H), 2.10 (s, 3H), 1.81 (s, 6H), 1.72 (s, 6H).

Step-c: Synthesis of 1-(4-((3R,5R)-adamantan-1-yl)-2-chlorobenzyl)-4-nitro-1H-pyrazole Intermediate-X)

[0574] This intermediate was prepared according to a similar procedure described for Intermediate-III by using Intermediate-Xb (0.3 g, 0.88 mmol, 1 eq.) and 4-nitropyrazole (0.12 g, 1.06 mmol, 1.2 eq.) to afford title product as an off-white solid (0.3 g, 91M). .sup.1H NMR (400 MHz, DMSO-d6) δ 8.99 (s, 1H), 8.28 (s, 1H), 7.41 (d, J=2.0 Hz, 1H), 7.35 (dd, J.sub.1=1.9 Hz, J.sub.2=8.3 Hz, 1H), 7.21 (d, J=8.3 Hz, 1H), 5.47 (s, 2H), 2.04 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H).

[0575] The below intermediates were prepared by a procedure similar to Intermediate-X using appropriate reactants and reagents and in presence of suitable solvents and appropriate reaction conditions.

TABLE-US-00016 Intermediate CP No. Reactant Structure Analytical data 226 XIII.1 [00438] [00439] .sup.1H NMR (400 MHz, DMSO-d6) δ 9.02 (s, 1H), 7.44 (s, 1H), 7.39 (s, 1H), 5.63 (s, 2H), 2.05 (s, 3H), 1.85 (d, J = 2.4 Hz, 6H), 1.72 (s, 6H). LC-MS: m/z 373.2 (M + H).sup.+ 228 XIII.2 [00440] [00441] .sup.1H NMR (400 MHz, DMSO-d6) δ 7.47 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 8.0 Hz, 1H), 7.42 (d, J = 1.6 Hz, 1H), 7.34-7.33 (m, 2H), 7.25 (d, J = 8.0 Hz, 1H), 7.21 (d, J = 2.0 Hz, 1H), 4.45 (s, 2H), 3.49 (t, J = 8.8 Hz, 2H), 3.07 (t, J = 8.0 Hz, 2H), 2.05 (s, 3H), 1.85 (s, 6H), 1.73 (s, 6H). LC-MS: m/z 423.2 (M + H).sup.+ 240 XIII.3 [00442] [00443] .sup.1H NMR (400 MHz, DMSO-d6) δ 8.39 (d, J = 1.2 Hz, 1H), 7.96 (d, J = 1.6 Hz, 1H), 7.44 (d, J = 2.0 Hz, 1H), 7.36-7.35 (m, 1H), 7.22 (d, J = 8.0 Hz, 1H), 5.39 (s, 2H), 2.05 (s, 3H), 1.84 (d, J = 2.8 Hz, 6H), 1.72 (s, 6H). LC-MS: m/z 372.2 (M + H).sup.+ 194 XIII.4 II.8 [00444] LC-MS: m/z 480.1 (M + H).sup.+ 195 XIII.5 III.3 [00445] LC-MS: m/z 494.1 (M + H).sup.+

Intermediate-XI

[0576] ##STR00446##

Step-a: Synthesis of N1-(4-((3R,5R)-adamantan-1-yl)-2-chlorophenyl)benzene-1,4-diamine (Intermediate-XI)

[0577] To a solution of Intermediate-VII (7 g, 18.3 mmol, 1 eq.) in THF:water (50 mL+50 mL), ammonium chloride (19.42 g, 36.6 mmol, 20 eq.) followed by Zinc dust (11.91 g, 183 mmol, 10 eq.) were added and stirred at RT for 16 h. Reaction mixture was diluted with ethyl acetate and filtered through celite. The filtrate was washed with water followed by brine. The organic layer was dried over anhydrous Sodium sulfate and concentrated in vacuo. The crude was washed with n-pentane and dried in vacuo to afford desired product as yellow gum (5.9 g, 91%). This was used in next step without further purification.

[0578] .sup.1H NM/R (400 MHz, DMSO-d6) δ 7.20 (d, J=1.9 Hz, 1H) 7.04 (dd, J.sub.1=2.0 Hz, J.sub.2=8.3 Hz, 1H), 6.84 (d, J=8.8 Hz, 2H), 6.78 (s, 1H), 6.72 (d, J=8.8 Hz, 1H), 6.54 (d, J=8.8 Hz, 2H), 4.85 (s, 2H), 2.02 (s, 3H), 1.78 (s, 6H), 1.70 (s, 6H); LC-MS: m/z 353.1 (M+H).sup.+

[0579] The below intermediates were prepared by a procedure similar to Intermediate-XI using appropriate reactants and reagents and in presence of suitable solvents and appropriate reaction conditions.

TABLE-US-00017 Intermediate CP No. Reactant Structure Analytical data 128 XI.1 VII.3 [00447] LC-MS: m/z 421.1 (M + H).sup.+  132, 133 XI.2 VII.5 [00448] .sup.1H NMR (400 MHz, DMSO- d6) δ 7.25-7.19 (m, 4H), 7.16- 7.14 (m, 1H), 7.06-7.02 (m, 2H), 6.91 (d, J = 8.4 Hz, 2H), 6.78 (d, J = 8.4 Hz, 1H), 6.58 (d, J = 8.4 Hz, 2H), 4.93 (s, 2H), 2.24 (s, 3H). LC-MS: m/z 309.0 (M + H).sup.+ 169 XI.3 VII.7 [00449] .sup.1H NMR (400 MHz, DMSO- d6) δ 9.35-8.91 (bs, 1H), 7.80- 7.78 (bs, 1H), 7.62-7.57 (m, 2H), 7.45 (d, J = 2.0 Hz, 1H), 7.35 (dd, J.sub.1 = 2.4 Hz, J.sub.2 = 8.8 Hz, 1H), 7.01 (d, J = 9.2 Hz, 1H), 2.07 (s, 3H), 1.87 (s, 6H), 1.74 (s, 6H). LC-MS: m/z 354.1 (M + H).sup.+ 191 XI.4 VII.8 [00450] .sup.1H NMR (400 MHz, DMSO- d6) δ 7.34 (s, 1H), 7.02-6.98 (m, 1H), 6.80-6.79 (m, 3H), 6.61-6.51 (m, 4H), 4.71 (s, 2H), 2.02 (s, 3H), 1.74 (s, 6H), 1.67 (s, 6H). LC-MS: m/z 319.1 (M + H).sup.+ 203 XI.5 I.24 [00451] .sup.1H NMR (400 MHz, DMSO- d6) δ 7.28 (d, J = 7.8 Hz, 1H), 7.21-7.17 (m, 1H), 7.10 (d, J = 3.9 Hz, 2H), 6.88 (t, J = 7.9 Hz, 1H), 6.35 (dd, J.sub.1 = 1.5 Hz, J.sub.2 = 8.3 Hz, 1H), 6.27 (m, 2H), 4.91 (s, 2H), 3.86 (s, 2H), 3.13 (m, 1H), 1.06 (d, J = 6.9 Hz, 6H). LC-MS: m/z 226.3 (M + H).sup.+ 228 XI.6 X.2 [00452] .sup.1H NMR (400 MHz, DMSO- d6) δ 7.38 (d, J = 1.6 Hz, 1H), 7.36-7.30 (m, 2H), 6.69 (d, J = 7.6 Hz, 1H), 5.84 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 8.0 Hz, 1H), 5.78 (d, J = 1.2 Hz, 1H), 4.68 (s, 2H), 4.18 (s, 2H), 3.26 (t, J = 8.0 Hz, 2H), 2.75 (t, J = 7.6 Hz, 2H), 2.05 (s, 3H), 1.85 (s, 6H), 1.73 (s, 6H). LC-MS: m/z 393.2 (M + H).sup.+  204, 237 261 XI.7 VII.9 [00453] .sup.1H NMR (400 MHz, DMSO- d6) δ 7.30 (s, 1H), 7.19 (s, 2H), 7.13 (s, 1H), 6.87-6.83 (m, 1H), 6.26 (s, 1H), 6.20 (d, J = 7.8 Hz, 1H), 6.10 (d, J = 7.8 Hz, 1H), 4.92 (s, 2H), 2.04 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 353.1 (M + H).sup.+ 232 XI.8 Int-X [00454] LC-MS: m/z 342.2 (M + H).sup.+ 226 XI.9 X.1 [00455] .sup.1H NMR (400 MHz, DMSO- d6) δ 8.08 (s, 1H), 7.37-7.30 (m, 2H), 7.20-7.10 (m, 1H), 5.25 (s, 2H), 5.17 (s, 2H), 2.04 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 343.2 (M + H).sup.+ 240 XI.10 X.3 [00456] .sup.1H NMR (400 MHz, DMSO- d6) δ 7.59 (s, 1H), 7.40-7.38 (m, 1H), 7.34-7.32 (m, 1H), 7.15 (d, J = 8.0 Hz, 1H), 6.24 (d, J = 1.2 Hz, 1H), 5.18 (s, 2H), 4.61 (s, 2H), 2.10 (s, 3H), 1.82 (s, 6H), 1.73 (s, 6H). LC- MS: m/z 342.2 (M + H).sup.+ 249 XI.11 VII.10 [00457] LC-MS: m/z 367.1 (M + H).sup.+  270, 314 XI.12 IX.1 [00458] .sup.1H NMR (400 MHz, DMSO- d6) δ 7.26 (d, J = 8.8 Hz, 2H), 6.72 (m, 4H), 6.56 (d, J = 2.0 Hz, 2H), 4.93 (s, 2H), 2.03 (s, 3H), 1.82 (s, 6H), 1.68 (s, 6H). 272 XI.13 VII.12 [00459] .sup.1H NMR (400 MHz, DMSO- d6) δ 9.16 (s, 1H), 7.92 (dd, J.sub.1 = 1.4 Hz, J.sub.2 = 7.8 Hz, 1H), 7.25-7.21 (m, 1H), 7.04 (d, J = 8.3 Hz, 2H), 6.91 (d, J = 8.8 Hz, 1H), 6.70 (d, J = 2.0 Hz, 2H), 6.64-6.60 (m, 1H), 3.89 (s, 3H), 3.62 (s, 2H).  284, 321 XI.14 Int-IX [00460] .sup.1H NMR (400 MHz, DMSO- d6) δ 7.40 (s, 1H), 7.23 (d, J = 8.8 Hz, 1H), 6.73 (d, J = 8.3 Hz, 3H), 6.58 (d, J = 8.8 Hz, 2H), 4.97 (s, 2H), 2.03 (bs, 3H), 1.82 (s, 6H), 1.71 (s, 6H).  271, 273 XI.15 VII.21 [00461] .sup.1H NMR (400 MHz, DMSO- d6) δ 7.08 (d, J = 8.8 Hz, 2H), 6.92 (d, J = 8.0 Hz, 2H), 6.83 (d, J = 2.4 Hz, 1H), 6.38 (d, J = 9.2 Hz, 2H), 5.59 (s, 2H), 3.00 (s, 2H), 2.02 (s, 3H), 1.78 (s, 6H), 1.70 (s, 6H). 289 311 XI.16 VII.13 [00462] .sup.1H NMR (400 MHz, DMSO- d6) δ 7.09 (d, J = 8.8 Hz, 2H), 6.81 (m, 2H), 6.57-6.55 (m, 4H), 4.96 (s, 2H), 3.09 (s, 3H), 2.02 (s, 3H), 1.79 (s, 6H), 1.70 (s, 6H). LC-MS: m/z 333.1 (M + H).sup.+  298, 299 XI.17 VII.15 [00463] .sup.1H NMR (400 MHz, DMSO- d6) δ 9.67 (s, 1H), 8.29 (dd, J.sub.1 = 1.6 Hz, J.sub.2 = 4.4 Hz, 1H), 8.17 (dd, J.sub.1 = 1.6 Hz, J.sub.2 = 7.6 Hz, 1H), 7.26-7.22 (m, 2H), 6.73 (dd, J.sub.1 = 4.8 Hz, J.sub.2 = 8.0 Hz, 1H), 6.57-6.53 (m, 2H), 4.87 (s, 2H), 3.87 (s, 3H). LC- MS: m/z 244.15 (M + H).sup.+ 319 XI.18 VII.16 [00464] .sup.1H NMR (400 MHz, DMSO- d6) δ 7.28 (s, 1H), 7.06 (d, J = 8.8 Hz, 2H), 6.78 (d, J = 8.8 Hz, 2H), 6.72 (d, J = 8.8 Hz, 2H), 6.51 (d, J = 8.4 Hz, 2H), 4.68 (s, 2H), 2.10 (bs, 1H), 1.61 (s, 2H), 1.45-1.33 (m, 8H), 1.15 (s, 2H), 0.83 (s, 6H). LC-MS: m/z 347.3 (M + H).sup.+ 320 XI.19 VII.17 [00465] .sup.1H NMR (400 MHz, DMSO- d6) δ 7.46 (s, 1H), 7.07 (t, J = 7.9 Hz, 2H), 6.90 (d, J = 8.8 Hz, 2H), 6.83 (m, 4H), 6.57 (m, 5H), 4.74 (s, 2H), 3.52 (t, J = 7.3 Hz, 2H), 1.52 (m, 2H), 1.32 (m, 2H), 0.87 (t, J = 6.9 Hz, 3H). 338 XI.20 VII.18 [00466] .sup.1H NMR (400 MHz, DMSO- d6) δ 7.85 (s, 1H), 7.56 (d, J = 8.8 Hz, 2H), 7.08 (s, 1H), 6.84 (d, J = 8.4 Hz, 2H), 6.70 (d, J = 8.0 Hz, 2H), 6.55 (d, J = 8.4 Hz, 2H), 4.84 (s, 2H), 2.04 (s, 9H), 1.64 (s, 6H). LC- MS: m/z 362.3 (M + H).sup.+ 339 XI.21 VIII.4 [00467] .sup.1H NMR (400 MHz, DMSO- d6) δ 9.76 (s, 1H), 7.48 (d, J = 8.4 Hz, 2H), 7.25 (d, J = 8.8 Hz, 2H), 7.87 (d, J = 8.0 Hz, 2H), 7.46 (d, J = 8.0 Hz, 2H), 4.82 (s, 2H), 2.69 (t, J = 8.4 Hz, 2H), 2.49-2.46 (m, 2H), 2.04 (s, 3H), 1.82 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 375.3 (M + H).sup.+ 345 XI.22 XI.16 [00468] .sup.1H NMR (400 MHz, DMSO- d6) δ 7.09 (d, J = 8.8 Hz, 2H), 6.86 (d, J = 8.3 Hz, 2H), 6.56 (t, J = 9.3 Hz, 4H), 5.27 (d, J = 7.8 Hz, 1H), 3.50-3.49 (m, 1H), 3.10 (s, 3H), 2.02 (s, 3H), 1.79 (s, 6H), 1.71 (s, 6H), 1.13 (d, J = 6.3 Hz, 6H).  358,  359, 376 XI.23 Int-VIII [00469] .sup.1H NMR (400 MHz, DMSO- d6) δ 10.06 (s, 1H), 7.66 (d, J = 8.8 Hz, 3H), 7.38-7.28 (m, 3H), 7.15-7.03 (m, 3H), 6.73 (d, J = 6.8 Hz, 1H), 5.28 (s, 2H), 2.05 (s, 3H), 1.85 (s, 6H), 1.73 (s, 6H). 360 XI.24 IX.2 [00470] .sup.1H NMR (400 MHz, DMSO- d6) δ 7.41-7.38 (m, 3H), 7.21- 7.12 (m, 3H), 6.84-6.78 (m, 3H), 6.63 (d, J = 8.0 Hz, 2H), 5.06 (s, 2H), 2.96-2.93 (m, 1H), 1.13 (d, J = 8.0 Hz, 6H). LC-MS: m/z 338.1 (M + H).sup.+ 383 XI.25 IX.3 [00471] .sup.1H NMR (400 MHz, DMSO- d6) δ 7.39 (d, J = 2.0 Hz, 1H), 7.21 (dd, J.sub.1 = 2.4 Hz, J.sub.2 = 8.8 Hz, 1H), 6.73-6.71 (m, 3H), 6.57 (d, J = 8.4 Hz, 2H), 4.97 (s, 2H), 2.13-2.11 (m, 1H), 1.65 (s, 2H), 1.49-1.31 (m, 8H), 1.16 (s, 2H), 0.84 (s, 6H). LC- MS: m/z 382.1 (M + H).sup.+  366, 367 XI.26 VIII.1 [00472] .sup.1H NMR (400 MHz, DMSO- d6) δ 9.65 (s, 1H), 7.52 (d, J = 8.4 Hz, 1H), 7.43 (s, 1H), 7.35 (dd, J.sub.1 = 1.2 Hz, J.sub.2 = 8.0 Hz, 1H), 7.16-7.08 (m, 3H), 6.75 (d, J = 7.6 Hz, 1H), 5.31 (s, 2H), 2.07 (s, 3H), 1.88 (s, 6H), 1.74 (s, 6H). LC-MS: m/z 381.1 (M + H).sup.+ 373 XI.27 VIII.2 [00473] .sup.1H NMR (400 MHz, DMSO- d6) δ 10.05 (s, 1H), 7.65 (d, J = 7.6 Hz, 2H), 7.32-7.27 (m, 4H), 7.09 (d, J = 7.6 Hz, 1H), 5.57 (s, 2H), 2.05 (s, 3H), 1.85 (s, 6H), 1.73 (s, 6H). 395 XI.28 VIII.3 [00474] .sup.1H NMR (400 MHz, DMSO- d6) δ 10.03 (s, 1H), 7.71-7.67 (m, 2H), 7.19-7.02 (m, 7H), 6.84-6.82 (m, 4H), 5.33 (s, 2H), 3.64 (t, J = 7.2 Hz, 2H), 1.60-1.54 (m, 2H), 1.34-13.2 (m, 2H), 0.88 (t, J = 7.6 Hz, 3H). LC-MS: m/z 360.2 (M + H).sup.+ 378 XI.29 VII.20 [00475] LC-MS: m/z 319.2 (M + H).sup.+ 348 XI.30 VII.19 [00476] LC-MS: m/z 319.5 (M + H).sup.+ 266 XI.31 VII.1 [00477] LC-MS: m/z 387.15 (M + H).sup.+ 521, 541, 605, 606, 607, 608, 613, 648 XI.32 VII.74 [00478] LC-MS: m/z 267.1 (M + H).sup.+  522, 558 XI.33 VII.75 [00479] LC-MS: m/z 281.2 (M + H).sup.+. 528 XI.34 VII.76 [00480] LC-MS: m/z 325.1 (M + H).sup.+. 535 XI.35 VII.77 [00481] LC-MS: m/z 233.1 (M + H).sup.+. 537 XI.36 VII.78 [00482] LC-MS: m/z 350.2 (M + H).sup.+. 538 XI.37 VII.79 [00483] .sup.1H NMR (400 MHz, DMSO-d.sub.6): δ 6.95 (d, J = 8.8 Hz, 2H), 6.8 (d, J = 8.4 Hz, 2H), 6.55 (dd, J.sub.1 = 5.2 Hz & J.sub.2 = 8.4 Hz, 4H), 4.98 (s, 2H), 3.08 (s, 3H), 2.57-2.55 (m, 1H), 2.28 (s, 1H), 2.15 (s, 1H), 1.63-1.41 (m, 4H), 1.35-1.07 (m, 4H). LC-MS: m/z 293.2 (M + H).sup.+. 542 XI.38 VII.80 [00484] LC-MS: m/z 267.1 (M + H).sup.+. 543, 544 XI.39 IX.6 [00485] LC-MS: m/z 288.0 (M + H).sup.+. 545 XI.40 VII.81 [00486] LC-MS: m/z 229.1 (M + H).sup.+. 546 XI.41 IX.7 [00487] LC-MS: m/z 302.1 (M + H).sup.+. 547 XI.42 VII.82 [00488] .sup.1H NMR (400 MHz, DMSO-d.sub.6): δ 6.80-6.73 (m, 4H), 6.63 (d, J = 8.8 Hz, 2H), 6.53 (d, J = 8.4 Hz, 2H), 4.87 (s, 2H), 3.71-3.69 (m, 4H), 3.05 (s, 3H), 2.95-2.92 (m, 4H). LC-MS: m/z 284.2 (M + H).sup.+. 548 XI.43 VII.83 [00489] .sup.1H NMR (400 MHz, DMSO-d.sub.6) δ 7.08 (d, J = 8.8 Hz, 2H), 6.86- 6.83 (m, 2H), 6.61-6.58 (m, 4H), 5.08 (s, 2H), 3.13 (s, 3H). LC-MS: m/z 283.1 (M + H).sup.+. 549 XI.44 VII.84 [00490] LC-MS: m/z 299.2 (M + H).sup.+. 550 XI.45 IX.7 [00491] LC-MS: m/z 302.1 (M + H).sup.+. 551 XI.46 VII.85 [00492] LC-MS: m/z 347.3 (M + H).sup.+. 552 XI.47 VII.86 [00493] LC-MS: m/z 317.2 (M + H).sup.+. 553 XI.48 VII.87 [00494] LC-MS: m/z 297.1 (M + H).sup.+. 554 XI.49 VII.88 [00495] LC-MS: m/z 249.1 (M + H).sup.+. 555 XI.50 VII.89 [00496] LC-MS: m/z 282.5 (M + H).sup.+. 556 XI.51 VII.90 [00497] LC-MS: m/z 253.2 (M + H).sup.+ 557 XI.52 VII.91 [00498] LC-MS: m/z 315.2 (M + H).sup.+ 560, 579, 580, 614, 619, 620, 621, 625, 627, 628, 629 XI.53 VII.92 [00499] LC-MS: m/z 295.2 (M + H).sup.+ Also for CP compounds 630, 631, 632, 633, 634, 635, 636, 637, 640, 653, 656, 657, 678, 679 561, 564 XI.54 IX.8 [00500] LC-MS: m/z 396.1 (M + H).sup.+. 563 XI.55 VII.93 [00501] .sup.1H NMR (400 MHz, DMSO-d.sub.6): δ 7.38 (d, J = 8.8 Hz, 2H), 6.79- 6.74 (m, 2H), 6.66-6.64 (m, 3H), 4.91 (s, 2H), 3.18 (s, 3H), 2.04 (s, 3H). 565 XI.56 VII.94 [00502] LC-MS: m/z 311.2 (M + H).sup.+. 566 XI.57 IX.9 [00503] procured 568 XI.58 VII.95 [00504] LC-MS: m/z 314.05 (M + H).sup.+. 569, 570 XI.59 IX.10 [00505] LC-MS: m/z 400.2 (M + H).sup.+ 571 XI.60 VII.96 [00506] LC-MS: m/z 339.1 (M + H).sup.+ 572 XI.61 VII.97 [00507] LC-MS: m/z 285.1 (M + H).sup.+ 573 XI.62 VII.98 [00508] .sup.1H NMR (400 MHz, DMSO-d.sub.6): δ 7.60-7.57 (m, 2H), 6.97-6.93 (m, 1H), 6.82-6.79 (m, 1H), 6.64 (d, J = 9.2 Hz, 2H), 5.25 (s, 2H), 3.20 (s, 3H). 574, 583, 584 XI.63 VII.99 [00509] LC-MS: m/z 295.2 (M + H).sup.+. 575 XI.64 IX.11 [00510] LC-MS: m/z 270.1 (M + H).sup.+. 576 XI.65 VII.100 [00511] LC-MS: m/z 268 (M + H).sup.+ 577 XI.66 VII.101 [00512] LC-MS: m/z 307.2 (M + H).sup.+ 578 XI.67 VII.102 [00513] LC-MS: m/z 282.0 (M + H).sup.+ 581 XI.68 VII.103 [00514] LC-MS: m/z 282.4 (M + H).sup.+ 582 XI.69 VII.104 [00515] LC-MS: m/z 296.15 (M + H).sup.+ 585 XI.70 VII.105 [00516] LC-MS: m/z 311.1 (M + H).sup.+ 586 XI.71 VIII.5 [00517] LC-MS: m/z 279.0 (M − H).sup.− 588 XI.72 VII.106 [00518] LC-MS: m/z 274.1 (M − H).sup.− 589 XI.73 VII.107 [00519] LC-MS: m/z 301.1 (M + H).sup.+ 590 XI.74 VII.108 [00520] LC-MS: m/z 297.2 (M − H).sup.− 592 XI.75 VII.109 [00521] LC-MS: m/z 331.0 (M + H).sup.+ 593 XI.76 VII.110 [00522] LC-MS: m/z 309.3 (M + H).sup.+ 595 XI.77 VII.112 [00523] LC-MS: m/z 326.0 (M + H).sup.+ 596 XI.78 VII.52 [00524] LC-MS: m/z 349.0 (M + H).sup.+ 597 XI.79 VII.113 [00525] LC-MS: m/z 288.1 (M + H).sup.+ 643, 654, 655 XI.80 VII.123 [00526] LC-MS: m/z 282.1 (M + H).sup.+ 599 XI.81 IX.13 [00527] LC-MS: m/z 317.2 (M + H).sup.+ 600 XI.82 IX.14 [00528] LC-MS: m/z 305.0 (M + H).sup.+ 601 XI.83 IX.15 [00529] LC-MS: m/z 289.0 (M + H).sup.+ 603 XI.84 VII.115 [00530] LC-MS: m/z 349.2 (M + H).sup.+ 609, 652, 673, XI.85 VII.116 [00531] LC-MS: m/z 296.2 (M + H).sup.+ 612 XI.86 VII.117 [00532] LC-MS: m/z 267.1 (M + H).sup.+ 615 XI.87 IX.16 [00533] LC-MS: m/z 335.05 (M + H).sup.+ 617 XI.88 VII.118 [00534] LC-MS: m/z 301.0 (M + H).sup.+ 618 XI.89 VII.119 [00535] LC-MS: m/z 285.2 (M + H).sup.+ 622 XI.90 VII.120 [00536] LC-MS: m/z 299.0 (M + H).sup.+ 624 XI.91 VII.121 [00537] LC-MS: m/z 271.1 (M + H).sup.+ 626 XI.92 VII.122 [00538] LC-MS: m/z 321.30 (M + H).sup.+ 641 XI.93 VII.62 [00539] LC-MS: m/z 335.05 (M + H).sup.+ 642 XI.94 VIII.6 [00540] LC-MS: m/z 309.1 (M + H).sup.+ 646 XI.95 VII.124 [00541] LC-MS: m/z 311.2 (M + H).sup.+ 647 XI.96 VII.125 [00542] LC-MS: m/z 297.1 (M + H).sup.+ 659 XI.97 VII.126 [00543] LC-MS: m/z 316.2 (M + H).sup.+ 660, 675, 676 XI.98  VII.63 [00544] LC-MS: m/z 369.00 (M + H).sup.+ 661, 662 XI.99 VII.62 [00545] LC-MS: m/z 335.05 (M + H).sup.+ 663  XI.100 VII.127 [00546] LC-MS: m/z 322.2 (M + H).sup.+ 665, 666, 669, 672  XI.101 VIII.8 [00547] LC-MS: m/z 329.1 (M + H).sup.+ 671, 681  XI.102 VII.128 [00548] LC-MS: m/z 329.2 (M + H).sup.+ 680  XI.103 VII.69 [00549] LC-MS: m/z 315.1 (M + H).sup.+ 682, 677  XI.104 VII.70 [00550] LC-MS: m/z 301.2 (M + H).sup.+

Intermediate-XII

[0580] ##STR00551##

Step-a: Synthesis of methyl 2-((4-((4-((3r,5r,7r)-adamantan-1-yl)-2-chlorophenyl) amino)phenyl)amino) nicotinate (Intermediate-XII)

[0581] A solution of Intermediate-XI (8 g, 22.72 mmol, 1 eq.) and methyl 2-chloronicotinate (4.27 g, 25 mmol, 1.1 eq.) in toluene (100 mL) was de-gassed by bubbling Nitrogen gas for 5 minutes. Cesium carbonate (11.1 g, 34.1 mmol, 1.5 eq.) was added followed by Palladium acetate (0.5 g, 2.27 mmol, 0.1 eq.) and rac. BINAP (2.12 g, 3.41 mmol, 0.15 eq.) and de-gassed again for 5 min. Reaction mixture was heated at 110° C. under stirring for 16 h. Reaction mixture was cooled to RT, diluted with ethyl acetate and filtered through celite. The organic layer was adsorbed over silica and purified by flash column chromatography. Desired product was eluted in 10% ethyl acetate in hexanes. Concentrated in vacuo to afford yellow solid (5.4 g, 49%).

[0582] .sup.1H NMR (400 MHz, DMSO-d6) δ 9.93 (s, 1H), 8.37 (dd, J.sub.1=2.0 Hz, J.sub.2=4.4 Hz, 1H), 8.22 (dd, J.sub.1=2.0 Hz, J.sub.2=7.6 Hz, 1H), 7.55 (d, J=8.8 Hz, 2H), 7.41 (s, 1H), 7.31 (d, J=1.6 Hz, 1H), 7.19-7.12 (m, 2H), 7.04 (d, J=8.8 Hz, 2H), 6.84-6.81 (m, 1H), 3.89 (s, 3H), 2.04 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H); LC-MS: m/z 488.1 (M+H).sup.+

[0583] The below intermediates were prepared by a procedure similar to Intermediate-XII using appropriate reactants and reagents employing suitable Pd catalysts and ligands and in presence of suitable solvents and appropriate reaction conditions.

TABLE-US-00018 Inter- mediate Reac- CP No. tant Structure Analytical data 57  XII.1  VII.1 [00552] .sup.1H NMR (500 MHz, CDCl.sub.3) δ 9.45 (s, 1H), 8.01 (s, 1H), 7.45-7.23. (d, 2H), 7.23-7.01 (m, 6H), 6.98-7.01 (d, 2H), 6.94 (s, 1H), 3.93 (s, 3H), 5.99 (s, 1H) 2.21-1.98 (m, 15H) LC-MS: m/z 521.2 (M + H).sup.+ 59  XII.2  XI.31 [00553] .sup.1H NMR (500 MHz, DMSO-d6) δ 9.45 (s, 1H), 8.01 (s, 1H), 7.49-7.33. (d, 2H), 7.23-7.01 (m, 5H), 6.91-7.04 (d, 2H), 6.94 (s, 1H), 3.93 (s, 3H), 5.99 (s, 1H) 2.21-1.98 (m, 15H) LC-MS: m/z 522.2 (M + H).sup.+ 60  XII.3  XI.31 [00554] LC-MS: m/z 535.6 (M + H).sup.+ 61  XII.4  XI.31 [00555] LC-MS: m/z 589.2 (M + H).sup.+ 62  XII.5  [00556] LC-MS: m/z 539.5 (M + H).sup.+ 65  XII.6  [00557] LC-MS: m/z 468.3 (M + H).sup.+ 66  XII.7  XI.1 [00558] LC-MS: m/z 556 (M + H).sup.+ 67  XII.8  XI.3 [00559] LC-MS: m/z 489 (M + H).sup.+ 146 XII.9  I.13 [00560] .sup.1H NMR (400 MHz, DMSO-d6) δ 9.29 (s, 1H), 7.89 (dd, J.sub.1 = 1.6 Hz, J.sub.2 = 8.0 Hz, 1H), 7.49-742 (m, 5H), 7.33-7.25 (m, 5H), 7.15-7.13 (m, 3H), 6.94-6.86 (m, 1H), 3.83 (s, 3H). LC-MS: m/z 370.1 (M + H).sup.+ 156 XII.10  Int-XI [00561] .sup.1H NMR (400 MHz, DMSO-d6) δ 9.05 (s, 1H), 7.93 (dd, J.sub.1 = 1.2 Hz, J.sub.2 = 3.6 Hz, 1H), 7.59 (s, 1H), 7.42- 7.34 (m, 3H), 7.21 (s, 2H), 7.13 (d, J = 8.8 Hz, 1H), 7.05 (d, J = 8.8 Hz, 2H), 3.87 (s, 3H), 2.04 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 488.1 (M + H).sup.+ 157 XII.11  Int-XI [00562] .sup.1H NMR (400 MHz, DMSO-d6) δ 8.77 (s, 1H), 8.38 (s, 1H), 7.95 (d, J = 5.6 Hz, 1H), 7.63 (d, J = 4.8 Hz, 1H), 7.60 (s, 1H), 7.34 (s, 1H), 7.22 (s, 2H), 7.18 (d, J = 8.8 Hz, 2H), 7.05 (d, J = 8.8 Hz, 2H), 3.89 (s, 3H), 2.05 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 488.1 (M + H).sup.+ 159 XII.12  Int-XI [00563] .sup.1H NMR (400 MHz, DMSO-d6) δ 9.96 (s, 1H), 8.88 (s, 1H), 8.69 (s, 1H), 7.58 (s, 1H), 7.50 (d, J = 8.8 Hz, 2H), 7.34 (s, 1H), 7.21 (s, 2H), 7.04 (d, J = 8.8 Hz, 2H), 4.38 (q, 2H), 2.05 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H), 1.36 (t, J = 7.2 Hz, 3H). LC-MS: m/z 503.2 (M + H).sup.+ 160 XII.13  Int-XI [00564] LC-MS: m/z 489.1 (M + H).sup.+ 163 XII.14  Int-XI [00565] LC-MS: m/z 502.1 (M + H).sup.+ 168 XII.15  Int-XI [00566] .sup.1H NMR (400 MHz, DMSO-d6) δ 9.17 (s, 1H), 7.70 (d, J = 8.8 Hz, 2H), 7.66 (d, J = 8.0 Hz, 1H), 7.37 (d, J = 7.2 Hz, 1H), 7.29 (d, J = 2.0 Hz, 1H), 7.26 (s, 1H), 7.14 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 8.8 Hz, 1H), 7.04 (t, J = 8.8 Hz, 3H), 6.98 (d, J = 8.4 Hz, 1H), 4.31 (q, 2H), 2.04 (s, 3H), 1.82 (s, 6H), 1.72 (s, 6H), 1.33 (t, J = 6.8 Hz, 3H). LC-MS: m/z 502.2 (M + H).sup.+ 169 XII.16  XI.3 [00567] .sup.1H NMR (400 MHz, DMSO-d6) δ 9.73 (s, 1H), 8.35-8.32 (m, 2H), 8.22 (dd, J.sub.1 = 1.6 Hz, J.sub.2 = 7.6 Hz, 1H), 8.17 (s, 1H), 7.91 (d, J = 8.8 Hz, 1H), 7.85 (dd, J.sub.1 = 2.8 Hz, J.sub.2 = 9.2 Hz, 1H), 7.34 (d, J = 2.4 Hz, 1H), 7.27 (dd, J.sub.1 = 2.4 Hz, J.sub.2 = 8.8 Hz, 1H), 6.98 (d, J = 8.8 Hz, 1H), 6.84 (dd, J.sub.1 = 4.4 Hz, J.sub.2 = 8.0 Hz, 1H), 3.90 (s, 3H), 2.06 (s, 3H), 1.86 (s, 6H), 1.74 (s, 6H). LC-MS: m/z 489.1 (M + H).sup.+ 191 XII.17  XI.4 [00568] .sup.1H NMR (400 MHz, DMSO-d6) δ 9.90 (s, 1H), 8.60 (m, 1H), 8.40 (m, 1H), 7.97 (s, 1H), 7.54 (d, J = 8.8 Hz, 2H), 7.13 (m, 1H), 7.03 (m, 3H), 6.81 (m, 3H), 3.92 (s, 3H), 2.05 (s, 3H), 1.84 (s, 6H), 1.73 (s, 6H). LC-MS: m/z 454.1 (M + H).sup.+ 202 236 XII.18  XI.8 [00569] .sup.1H NMR (400 MHz, DMSO-d6) δ 9.78 (s, 1H), 8.40 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 5.2 Hz, 1H), 8.21 (s, 1H), 8.19- 8.18 (m, 1H), 7.72 (s, 1H), 7.31 (d, J = 1.6 Hz, 1H), 7.29 (d, J = 2.0 Hz, 1H), 6.95 (d, J = 8.4 Hz, 1H), 6.80 (dd, J.sub.1 = 4.4 Hz, J.sub.2 = 7.2 Hz, 1H), 5.37 (s, 2H), 3.88 (s, 3H), 2.04 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H). LC- MS: m/z 477.2 (M + H).sup.+ 203 XII.19  XI.5 [00570] .sup.1H NMR (400 MHz, DMSO-d6) δ 10.04 (s, 1H), 8.36 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 4.9 Hz, 1H), 8.24 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 7.8 Hz, 1H), 7.62 (d, J == 1.0 Hz, 1H), 7.36 (s, 1H), 7.30 (d, J = 7.3 Hz, 1H), 7.24-7.11 (m, 4H), 6.88-6.85 (m, 1H), 6.78 (d, J = 7.8 Hz, 1H), 4.06 (s, 2H), 3.88 (s, 3H), 3.17 (m, 1H), 1.15 (d, J = 6.8 Hz, 6H). LC-MS: m/z 361.2 (M + H).sup.+ 204 XII.20  XI.7 [00571] .sup.1H NMR (400 MHz, DMSO-d6) δ 10.04 (s, 1H), 8.39 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 4.8 Hz, 1H), 8.25 (dd, J.sub.1 = 1.6 Hz, J.sub.2 = 7.6 Hz, 1H), 7.57 (s, 1H), 7.48 (s, 1H), 7.36-7.31 (m, 2H), 7.24 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 8.4 Hz, 1H), 7.15 (d, J = 6.0 Hz, 2H), 6.88 (dd, J.sub.1 = 4.8 Hz, J.sub.2 = 7.6 Hz, 1H), 6.70-6.68 (m, 1H), 3.89 (s, 3H), 2.05 (s, 3H), 1.85 (s, 6H), 1.73 (s, 6H). LC-MS: m/z 488.3 (M + H).sup.+ 205 XII.21  Int-XI [00572] .sup.1H NMR (400 MHz, DMSO-d6) δ 9.68 (s, 1H), 8.43 (s, 1H), 8.35 (s, 1H), 7.68 (d, J = 8.8 Hz, 2H), 7.38 (s, 1H), 7.31 (d, J = 2.0 Hz, 1H), 7.16 (d, J = 2.0 Hz, 1H), 7.12 (d, J = 8.8 Hz, 1H), 7.06 (d, J = 8.8 Hz, 2H), 3.89 (s, 3H), 2.05 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H). LC- MS: m/z 489.3 (M + H).sup.+ 206 XII.22  Int-XI [00573] .sup.1H NMR (400 MHz, DMSO-d6) δ 8.43 (dd, J.sub.1 = 2.9 Hz, J.sub.2 = 4.4 Hz, 2H), 8.38 (s, 1H), 7.71 (t, J = 2.9 Hz, 1H), 7.20-7.17 (m, 2H), 7.06-7.04 (m, 4H), 3.85 (s, 3H), 2.04 (s, 3H), 1.82 (s, 6H), 1.72 (s, 6H). 207 XII.23  Int-XI [00574] .sup.1H NMR (400 MHz, DMSO-d6) δ 8.82 (s, 1H), 8.21 (d, J = 5.4 Hz, 1H), 7.54 (s, 1H), 7.45 (d, J = 2.4 Hz, 1H), 7.34 (s, 1H), 7.20 (s, 2H), 7.11- 7.04 (m, 4H), 6.93- 6.91 (m, 1H), 3.82 (s, 3H), 2.04 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H).  211, 268 XII.24  XI.1 [00575] LC-MS: m/z 570.2 (M + H).sup.+ 226 XII.25  XI.9 [00576] LC-MS: m/z 478.2 (M + H).sup.+ 228 XII.26  XI.6 [00577] .sup.1H NMR (400 MHz, DMSO-d6) δ 9.96 (s, 1H), 8.33 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 5.2 Hz, 1H), 8.21 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 8.0 Hz, 1H), 7.42- 7.40 (m, 2H), 7.33 (dd, J.sub.1 = 1.6 Hz, J.sub.2 = 8.0 Hz, 1H), 7.00-6.92 (m, 3H), 6.82 (dd, J.sub.1 = 4.8 Hz, J.sub.2 = 7.6 Hz, 1H), 4.31 (s, 2H), 3.88 (s, 3H), 3.37 (t, J = 8.0 Hz, 2H), 2.89 (t, J = 8.2 Hz, 2H), 2.05 (s, 3H), 1.85 (d, J = 2.4 Hz, 6H), 1.73 (s, 6H). LC-MS: m/z 528.2 (M + H).sup.+ 240 XII.27  XI.10 [00578] LC-MS: m/z 477.2 (M + H).sup.+ 249 XII.28  XI.11 [00579] .sup.1H NMR (400 MHz, DMSO-d6) δ 9.79 (s, 1H), 8.31 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 4.8 Hz, 1H), 8.19 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 8.0 Hz, 1H), 7.48 (d, J = 2.0 Hz, 1H), 7.43-7.39 (m, 3H), 7.29 (d, J = 8.0 Hz, 1H), 6.77 (dd, J.sub.1 = 4.4 Hz, J.sub.2 = 8.4 Hz, 1H), 6.52 (d, J = 8.8 Hz, 2H), 3.88 (s, 3H), 3.18 (s, 3H), 2.07 (s, 3H), 1.89 (s, 6H), 1.74 (s, 6H). LC-MS: m/z 502.1 (M + H).sup.+ 261 XII.29  XI.7 [00580] .sup.1H NMR (400 MHz, DMSO-d6) δ 9.21 (s, 1H), 7.69 (t, J = 8.0 Hz, 1H), 7.43-7.38 (m, 4H), 7.32 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 10.8 Hz, 2H), 7.20 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 8.4 Hz, 1H), 7.13 (t, J = 8.0 J = 8.0 Hz, 1H), 6.63 (t, J = 8.4 Hz, 1H), 4.28-4.23 (q, 2H), 2.05 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H), 1.26 (t, J = 7.2 Hz, 3H). LC-MS: m/z 500.1 (M − H).sup.− 262 XII.30  Int-XI [00581] .sup.1H NMR (400 MHz, DMSO-d6) δ 8.99 (s, 1H), 7.56 (t, J = 8.0 Hz, 1H), 7.47 (d, J = 8.8 Hz, 2H), 7.28- 7.23 (m, 2H), 7.13 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 8.8 Hz, 1H), 7.11-6.93 (m, 4H), 6.66 (d, J = 8.4 Hz, 1H), 6.58 (d, J = 7.2 Hz, 1H), 2.04 (s, 3H), 1.81 (s, 6H), 1.71 (s, 6H), 1.42 (s, 18H). LC- MS: m/z 645.1 (M + H).sup.+ 263 XII.31  XI.1 [00582] .sup.1H NMR (400 MHz, DMSO-d6) δ 11.68 (s, 1H), 9.11 (s, 1H), 8.53 (d, J = 1.6 Hz, 1H), 8.29 (d, J = 2.4 Hz, 1H), 7.61 (s, 1H), 7.55 (s, 1H), 7.51- 7.46 (m, 2H), 7.36 (s, 1H), 7.23 (s, 1H), 3.78 (s, 3H), 1.97 (s, 3H), 1.72-1.61 (m, 13H). LC-MS: m/z 520.2 (M + H).sup.+ 267 XII.32  XI.1 [00583] .sup.1H NMR (400 MHz, DMSO-d6) δ 8.84 (s, 1H), 8.56 (dd, J.sub.1 = 1.6 Hz, J.sub.2 = 6.4 Hz, 2H), 8.12 (s, 1H), 7.91 (d, J = 2.4 Hz, 1H), 7.41 (d, J = 2.0 Hz, 1H), 7.36-7.28 (m, 2H), 6.84 (s, 1H), 6.74 (d, J = 15.6 Hz, 2H), 3.89 (s, 3H), 2.05 (s, 3H), 1.84 (s, 6H), 1.73 (s, 6H). LC-MS: m/z 556.0 (M + H).sup.+ 271 XII.33  XI.15 [00584] .sup.1H NMR (400 MHz, DMSO-d6) δ 10.25 (s, 1H), 8.47 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 4.8 Hz, 1H), 8.33-8.30 (m, 2H), 7.96 (dd, J.sub.1 = 2.4 Hz, J.sub.2 = 8.4 Hz, 1H), 7.30 (d, J = 8.4 Hz, 1H), 7.13 (d, J = 8.8 Hz, 2H), 6.98 (dd, J.sub.1 = 4.4 Hz, J.sub.2 = 7.6 Hz, 1H), 6.45 (d, J = 8.8 Hz, 2H), 3.93 (s, 3H), 3.09 (s, 3H), 2.02 (s, 3H), 1.80 (s, 6H), 1.71 (s, 6H). LC-MS: m/z 536.1 (M + H).sup.+ 273 XII.34  XI.15 [00585] .sup.1H NMR (400 MHz, DMSO-d6) δ 9.31 (s, 1H), 7.92 (dd, J.sub.1 = 1.2 Hz, J.sub.2 = 7.6 Hz, 1H), 7.77-7.74 (m, 1H), 7.61 (d, J = 2.4 Hz, 1H), 7.56 (dd, J.sub.1 = 2.4 Hz, J.sub.2 = 8.8 Hz, 1H), 7.52-7.46 (m, 2H), 7.36 (d, J = 8.4 Hz, 1H), 7.26 (d, J = 8.0 Hz, 1H), 7.13 (d, J = 8.8 Hz, 1H), 6.94 (t, J = 7.6 Hz, 1H), 6.47 (d, J = 9.2 Hz, 1H), 3.86 (s, 3H), 3.31 (s, 3H), 2.02 (s, 3H), 1.80 (s, 6H), 1.71 (s, 6H). LC-MS: m/z 535.1 (M + H).sup.+ 275 XII.35  XI.3 [00586] .sup.1H NMR (400 MHz, CDCl3) δ 9.19 (s, 1H), 8.11 (d, J = 2.4 Hz, 1H), 7.95 (dd, J.sub.1 = 1.6 Hz, J.sub.2 = 8.4 Hz, 1H), 7.41 (dd, J.sub.1 = 2.8 Hz, J.sub.2 = 8.8 Hz, 1H), 7.34 (d, J = 8.8 Hz, 2H), 7.30-7.26 (m, 3H), 6.92-6.86 (m, 2H), 6.69 (t, J = 8.0 Hz, 1H), 6.63 (s, 1H), 3.91 (s, 3H), 2.10 (s, 3H), 1.91 (s, 6H), 1.81-1.73 (m, 6H). LC-MS: m/z 454.1 (M + H).sup.+ 284 XII.36  XI.14 [00587] .sup.1H NMR (400 MHz, DMSO-d6) δ 9.23 (s, 1H), 7.89 (d, J = 1.9 Hz, 1H), 7.76 (m, 1H), 7.49 (m, 2H), 7.26 (d, J = 8.8 Hz, 2H), 7.10 (m, 2H), 6.97 (d, J = 8.8 Hz, 2H), 6.77 (m, 1H), 3.86 (s, 3H), 2.05 (s, 3H), 1.81 (s, 6H), 1.70 (s, 6H). 289 XII.37  XI.16 [00588] .sup.1H NMR (400 MHz, DMSO-d6) δ 7.67- 7.59 (m, 2H), 7.34- 7.27 (m, 2H), 7.12 (d, J = 8.8 Hz, 2H), 6.88 (d, J = 8.8 Hz, 2H), 6.65 (d, J = 8.4 Hz, 2H), 6.55 (d, J = 8.8 Hz, 2H), 4.01-3.95 (m, 2H), 3.71-3.66 (m, 2H), 3.12 (s, 3H), 2.03 (s, 3H), 1.84 (s, 6H), 1.68 (s, 6H), 1.16 (t, J = 6.8 Hz, 3H), 1.07 (t, J = 7.6 Hz, 3H). LC-MS: m/z 509.1 (M + H).sup.+ 290 XII.38  XI.16 [00589] .sup.1H NMR (400 MHz, DMSO-d6) δ 9.23 (s, 1H), 7.88 (d, J = 8.4 Hz, 1H), 7.75-7.73 (m, 1H), 7.52-7.46 (m, 1H), 7.42-7.36 (m, 1H), 7.26 (d, J = 8.8 Hz, 2H), 7.15 (d, J = 8.8 Hz, 2H), 7.06 (d, J = 8.4 Hz, 1H), 6.99-6.95 (m, 2H), 6.75-6.71 (m, 1H), 4.33-4.31 (m, 2H), 3.23 (s, 3H), 2.05 (s, 3H), 1.85 (s, 6H), 1.73 (s, 6H), 1.34 (t, J = 6.9 Hz, 3H). LC-MS: m/z 481.0 (M + H).sup.+ 311 XII.39  XI.16 [00590] LC-MS: m/z 482.1 (M + H).sup.+ 314 XII.40  XI.12 [00591] .sup.1H NMR (400 MHz, DMSO-d6) δ 10.02 (s, 1H), 8.39 (dd, J.sub.1 = 1.9 Hz, J.sub.2 = 4.9 Hz, 1H), 6.25 (dd, J.sub.1 = 1.9 Hz, J.sub.2 = 7.8 Hz, 1H), 7.70 (d, J = 8.8 Hz, 2H), 7.34 (d, J = 8.9 Hz, 2H), 6.99 (d, J = 8.8 Hz, 2H), 6.89- 6.88 (m, 3H), 3.90 (s, 3H), 2.05 (s, 3H), 1.84 (s, 6H), 1.73 (s, 6H). 319 XII.41  XI.18 [00592] .sup.1H NMR (400 MHz, DMSO-d6) δ 9.07 (s, 1H), 7.78 (s, 1H), 7.66-7.62 (m, 3H), 7.34 (d, J = 7.6 Hz, 1H), 7.16 (d, J = 8.8 Hz, 2H), 7.01-6.92 (m, 5H), 4.33-4.28 (m, 2H), 2.12 (s, 1H), 1.65 (s, 2H), 1.49- 1.31 (m, 11H), 1.17 (s, 2H), 0.85 (s, 6H). LC-MS: m/z 496.3 (M + H).sup.+ 320 XII.42  XI.19 [00593] .sup.1H NMR (400 MHz, DMSO-d6) δ 9.12 (s, 1H), 7.91 (s, 1H), 7.65 (m, 3H), 7.36 (d, J = 6.9 Hz, 1H), 7.11 (t, J = 7.8 Hz, 2H), 7.02 (m, 7H), 6.65 (m, 3H), 4.32 (m, 2H), 3.56 (t, J = 7.3 Hz, 2H), 1.50 (m, 2H), 1.30 (m, 5H), 0.88 (t, J = 7.3 Hz, 3H). 321 XII.43  XI.14 [00594] .sup.1H NMR (400 MHz, DMSO-d6) δ 9.34 (s, 1H), 7.85 (d, J = 8.8 Hz, 2H), 7.70 (t, J = 7.4 Hz, 1H),7.47 (d, J = 2.4 Hz, 1H), 7.42 (d, J = 7.4 Hz, 1H), 7.30 (dd, J.sub.1 = 2.5 Hz, J.sub.2 = 8.8 Hz, 1H), 7.03 (d, J = 8.8 Hz, 1H), 6.92 (m, 3H), 4.32 (m, 2H), 2.05 (s, 3H), 1.85 (s, 6H), 1.72 (s, 6H), 1.33 (t, J = 6.8 Hz, 3H). 322 XII.44  XI.16 [00595] .sup.1H NMR (400 MHz, DMSO-d6) δ 8.75 (d, J = 2.4 Hz, 1H), 8.15 (dd, J.sub.1 = 2.4 Hz, J.sub.2 = 8.8 Hz, 2H), 7.36 (d, J = 8.8 Hz, 2H), 7.15- 7.12 (m, 4H), 7.05 (d, J = 9.2 Hz, 2H), 6.91 (t, J = 6.0 Hz, 3H), 3.85 (s, 6H), 3.28 (s, 3H), 2.06 (s, 3H), 1.87 (s, 6H), 1.74 (s, 6H). LC-MS: m/z 603.3 (M + H).sup.+ 338 XII.45  XI.20 [00596] .sup.1H NMR (400 MHz, DMSO-d6) δ 9.21 (s, 1H), 8.27 (s, 1H), 7.75 (d, J = 8.8 Hz, 2H), 7.70-7.63 (m, 3H), 7.38 (t, J = 7.6 Hz, 1H), 7.18 (s, 1H), 7.08 (d, J = 8.4 Hz, 2H), 6.99 (d, J = 8.0 Hz, 1H), 6.91 (d, J = 8.4 Hz, 2H), 4.34- 4.29 (m, 2H), 2.05 (s, 9H), 1.65 (s, 6H), 1.34 (t, J = 7.2 Hz, 3H). LC-MS: m/z 511.3 (M + H).sup.+ 339 XII.46  XI.21 [00597] .sup.1H NMR (400 MHz, DMSO-d6) δ 9.80 (s, 1H), 9.25 (s, 1H), 7.88 (d, J = 7.2 Hz, 1H), 7.49 (d, J = 8.8 Hz, 2H), 7.37 (t, J = 8.8 Hz, 1H), .sup.1H NMR (400 MHz, DMSO-d6) δ 7.27- 7.23 (m, 4H), 7.17- 7.12 (m, 3H), 6.76 (t, J = 7.6 Hz, 1H), 3.84 (s, 3H), 3.30 (t, J = 7.2 Hz, 2H), 2.60 (t, J = 7.6 Hz, 2H), 2.04 (s, 3H), 1.82 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 509.3 (M + H).sup.+ 345 XII.47  XI.22 [00598] LC-MS: m/z 509.4 (M + H).sup.+ 352 XII.48  XI.30 [00599] .sup.1H NMR (400 MHz, DMSO-d6) δ 8.82 (s, 1H), 8.26 (s, 1H), 8.12 (d, J = 6.8 Hz, 1H), 7.73 (d, J = 7.6 Hz, 1H), 7.60-7.41 (m, 2H), 7.29-7.21 (m, 4H), 7.08 (t, J = 8.8 Hz, 5H), 2.08 (s, 3H), 1.84 (s, 6H), 1.73 (s, 6H). LC-MS: m/z 423.3 (M + H).sup.+ 358 XII.49  XI.28 [00600] .sup.1H NMR (400 MHz, DMSO-d6) δ 10.24 (s, 1H), 10.19 (s, 1H), 8.45 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 4.8 Hz, 1H), 8.29 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 7.6 Hz, 1H), 8.17 (s, 1H), 8.03 (dd, J.sub.1 = 1.2 Hz, J.sub.2 = 8.0 Hz, 1H), 7.70 (d, J = 8.8 Hz, 2H), 7.60 (d, J = 8.0 Hz, 1H), 7.48 (t, J = 8.0 Hz, 1H), 7.33 (d, J = 8.8 Hz, 2H), 6.94 (dd, J.sub.1 = 4.8 Hz, J.sub.2 = 8.0 Hz, 1H), 3.92 (s, 3H), 2.06 (s, 3H), 1.86 (d, J = 2.4 Hz, 6H), 1.74 (s, 6H). LC-MS: m/z 482.3 (M + H).sup.+ 359 XII.50  XI.28 [00601] .sup.1H NMR (400 MHz, DMSO-d6) δ 10.14 (s, 1H), 8.65 (s, 1H), 7.69-7.67 (m, 3H), 7.61 (s, 1H), 7.45- 7.38 (m, 5H), 7.33- 7.31 (m, 3H), 3.83 (s, 3H), 2.05 (s, 3H), 1.85 (d, J = 2.8 Hz, 6H), 1.73 (s, 6H). LC- MS: m/z 481.2 (M + H).sup.+ 360 XII.51  XI.24 [00602] .sup.1H NMR (400 MHz, DMSO-d6) δ 9.26 (s, 1H), 7.90 (d, J = 7.9 Hz, 1H), 7.45 (m, 4H), 7.37-7.07 (m, 9H), 6.79 (t, J = 7.8 Hz, 1H), 3.86 (s, 3H), 2.97 (m, 1H), 1.20 (d, J = 6.9 Hz, 6H). 362 XII.52  XI.16 [00603] .sup.1H NMR (400 MHz, DMSO-d6) δ 7.57 (s, 1H), 7.24-7.19 (m, 3H), 7.01 (d, J = 8.8 Hz, 2H), 6.94 (d, J = 8.8 Hz, 2H), 6.83 (d, J = 8.3 Hz, 2H), 6.68 (d, J = 8.3 Hz, 1H), 6.53 (d, J = 8.3 Hz, 1H), 3.75 (s, 6H), 3.19 (s, 3H), 2.04 (s, 3H), 1.82 (s, 6H), 1.72 (s, 6H). 366 XII.53  XI.26 [00604] .sup.1H NMR (400 MHz, DMSO-d6) δ 10.24 (s, 1H), 9.96 (s, 1H), 8.45 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 4.8 Hz, 1H), 8.30 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 7.6 Hz, 1H), 8.23 (s, H), 8.07-8.04 (m, 1H), 7.64 (d, J = 8.0 Hz, 1H), 7.55-7.46 (m, 3H), 7.38 (dd, J.sub.1 = 2.4 Hz, J.sub.2 = 8.0 Hz, 1H), 6.95 (dd, J.sub.1 = 4.8 Hz, J.sub.2 = 7.6 Hz, 1H), 3.92 (s, 3H), 2.08 (s, 3H), 1.89 (s, 6H), 1.75 (s, 6H). LC-MS: m/z 516.2 (M + H).sup.+ 367 XII.54  XI.26 [00605] .sup.1H NMR (400 MHz, DMSO-d6) δ 10.00 (s, 1H), 9.42 (s, 1H), 7.93 (dd, J.sub.1 = 1.6 Hz, J.sub.2 = 8.0 Hz, 1H), 7.83 (s, 1H), 7.70-7.60 (m, 1H), 7.51-7.34 (m, 5H), 7.40-7.30 (m, 2H), 6.90-6.86 (m, 1H), 3.87 (s, 3H), 2.07 (s, 3H), 1.88 (d, J = 2.4 Hz, 6H), 1.74 (s, 6H). LC-MS: m/z 515.3 (M + H).sup.+ 373 XII.55  XI.27 [00606] .sup.1H NMR (400 MHz, DMSO-d6) δ 10.63 (s, 1H), 10.23 (s, 1H), 9.15 (d, J = 1.6 Hz, 1H), 8.50 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 4.8 Hz, 1H), 8.35 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 7.6 Hz, 1H), 7.70- 7.67 (m, 3H), 7.63- 7.61 (m, 1H), 7.33 (d, J = 8.8 Hz, 2H), 7.02 (dd, J.sub.1 = 4.4 Hz, J.sub.2 = 7.6 Hz, 1H), 3.94 (s, 3H), 2.06 (s, 3H), 1.87 (s, 6H), 1.74 (s, 6H). LC- MS: m/z 516.2 (M + H).sup.+ 375 352 XII.56  XII.48 [00607] .sup.1H NMR (400 MHz, DMSO-d6) δ 7.71 (s, 1H), 7.16-6.77 (m, 13H), 4.07-4.00 (m, 2H), 2.87 (t, J = 7.6 Hz, 2H), 2.59 (d, J = 8.0 Hz, 2H), 2.04 (s, 3H), 1.81 (s, 6H), 1.69 (s, 6H), 1.15 (t, J = 4.0 Hz, 3H), LC- MS: m/z 495.3 (M + H).sup.+ 376 XII.57  XI.28 [00608] .sup.1H NMR (400 MHz, DMSO-d6) δ 10.09 (s, 1H), 7.87 (s, 1H), 7.67 (d, J = 8.8 Hz, 2H), 7.54 (s, 1H), 7.38 (d, J = 18.4 Hz, 1H), 7.34-7.28 (m, 4H), 7.20-7.10 (m, 1H), 7.85 (d, J = 8.0 Hz, 1H), 6.70 (d, J = 8.4 Hz, 1H), 3.78 (s, 3H), 3.72 (s, 3H), 2.06 (s, 3H), 1.86 (d, J = 2.4 Hz, 6H), 1.74 (s, 6H). LC-MS: m/z 511.2 (M + H).sup.+ 377 XII.58  XI.30 [00609] .sup.1H NMR (400 MHz, DMSO-d6) δ 8.23 (s, 1H), 7.93 (s, 1H), 7.20 (d, J = 8.8 Hz, 2H), 7.03-6.97 (m, 6H), 6.06 (d, J = 2.0 Hz, 1H), 6.00 (d, J = 2.0 Hz, 1H), 3.74 (s, 3H), 3.73 (s, 3H), 3.67 (s, 3H), 2.04 (s, 3H), 1.82 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 513.3 (M + H).sup.+ 379 XII.59  XI.16 [00610] .sup.1H NMR (400 MHz, DMSO-d6) δ 8.82 (s, 1H), 7.36 (d, J = 2.4 Hz, 1H), 7.24 (d, J = 8.8 Hz, 2H), 7.10 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 5.2 Hz, 4H), 6.97 (d, J = 8.4 Hz, 2H), 6.90 (d, J = 8.8 Hz, 2H), 3.85 (s, 3H), 3.72 (s, 3H), 3.21 (s, 3H), 2.04 (s, 3H), 1.83 (s, 6H), 1.76 (s, 6H). LC- MS: m/z 497.3 (M + H).sup.+ 380 XII.60  XI.30 [00611] .sup.1H NMR (400 MHz, DMSO-d6) δ 9.29 (s, 1H), 8.03 (s, 1H), 7.82 (d, J = 8.8 Hz, 1H), 7.22 (d, J = 6.0 Hz, 2H), 7.13 (d, J = 8.8 Hz, 2H), 7.07 (d, J = 8.8 Hz, 2H), 7.02 (d, J = 8.0 Hz, 2H), 6.41 (d, J = 2.4 Hz, 1H), 6.32 (dd, J.sub.1 = 2.4 Hz, J.sub.2 = 9.2 Hz, 1H), 3.81 (s, 3H), 3.69 (s, 3H), 2.05 (s, 3H), 1.83 (d, J = 2.8 Hz, 6H), 1.73 (s, 6H). LC-MS: m/z 483.3 (M + H).sup.+ 382 XII.61  XI.14 [00612] .sup.1H NMR (400 MHz, DMSO-d6) δ 10.01 (s, 1H), 8.38 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 4.9 Hz, 1H), 8.25 (dd, J.sub.1 = 1.9 Hz, J.sub.2 = 7.8 Hz, 1H), 7.69 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 6.8 Hz, 2H), 7.49 (d, J = 2.5 Hz, 1H), 7.32 (dd, J.sub.1 = 2.4 Hz, J.sub.2 = 8.8 Hz, 1H), 6.98 (d, J = 8.3 Hz, 1H), 6.95 (dd, J.sub.1 = 1.9 Hz, J.sub.2 = 6.8 Hz, 2H), 6.87 (dd, J.sub.1 = 4.4 Hz, J.sub.2 = 7.3 Hz, 1H), 3.90 (s, 3H), 2.06 (s, 3H), 1.86 (s, 6H), 1.73 (s, 6H). LC- MS: m/z 489.1 (M + H).sup.+ 383 XII.62  XI.25 [00613] .sup.1H NMR (400 MHz, DMSO-d6) δ 9.24 (s, 1H), 7.88 (dd, J.sub.1 = 1.6 Hz, J.sub.2 = 8.0 Hz, 1H), 7.50 (d, J = 2.4 Hz, 1H), 7.39-7.32 (m, 2H), 7.26 (d, J = 8.8 Hz, 2H), 7.10-7.03 (m, 2H), 6.95 (d, J = 8.8 Hz, 2H), 6.77 (t, J = 8.0 Hz, 1H), 3.85 (s, 3H), 2.16- 2.12 (m, 1H), 1.69 (s, 2H), 1.53-1.35 (m, 8H), 1.18 (s, 2H), 0.86 (s, 6H). 384 XII.63  XI.25 [00614] .sup.1H NMR (400 MHz, DMSO-d6) δ 10.02 (s, 1H), 8.38 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 4.8 Hz, 1H), 8.25 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 7.6 Hz, 1H), 7.70-7.67 (m, 2H), 7.48 (d, J = 2.4 Hz, 1H), 7.33-7.30 (m, 1H), 6.98-6.93 (m, 3H), 6.89-6.86 (m, 1H), 3.90 (s, 3H), 2.14-2.13 (m, 1H), 1.69-1.68 (m, 2H), 1.52-1.35 (m, 8H), 1.18 (s, 2H), 0.86 (s, 6H). 395 XII.64  XI.28 [00615] .sup.1H NMR (400 MHz, DMSO-d6) δ 10.17 (s, 1H), 9.41 (s, 1H), 7.92 (dd, J.sub.1 = 1.2 Hz, J.sub.2 = 7.6 Hz, 1H), 7.8 (s, 1H), 7.69 (d, J = 9.2 Hz, 2H), 7.64 (d, J = 7.6 Hz, 1H), 7.52- 7.44 (m, 3H), 7.31 (d, J = 8.4 Hz, 1H), 7.22- 7.18 (m, 2H), 7.03 (d, J = 8.8 Hz, 2H), 6.89- 6.79 (m, 4H), 3.87 (s, 3H), 3.65 (t, J = 7.6 Hz, 2H), 1.58-1.51 (m, 2H), 1.38-1.30 (m, 2H), 0.88 (t, J = 7.6 Hz, 3H). LC- MS: m/z 494.3 (M + H).sup.+ 398 XII.65  XI.28 [00616] .sup.1H NMR (400 MHz, DMSO-d6) δ 10.21- 10.17 (m, 2H), 8.44 (d, J = 2.8 Hz, 1H), 8.27 (dd, J.sub.1 = 1.6 Hz, J.sub.2 = 8.0 Hz, 1H), 8.15 (s, 1H), 8.01 (d, J = 8.4 Hz, 1H), 7.69 (d, J = 8.8 Hz, 2H), 7.59 (d, J = 8.0 Hz, 1H), 7.46 (t, J = 8.0 Hz, 1H), 7.19 (t, J = 8.4 Hz, 2H), 7.02 (d, J = 8.8 Hz, 2H), 6.92 (dd, J.sub.1 = 4.8 Hz, J.sub.2 = 8.0 Hz, 1H), 6.85-6.77 (m, 3H), 3.91 (s, 3H), 3.64 (t, J = 7.2 Hz, 2H), 1.55-1.52 (m, 2H), 1.35-1.29 (m, 2H), 0.87 (t, J = 4.8 Hz, 3H). LC-MS: m/z 495.3 (M + H).sup.+ 420 XII.66  XI.16 [00617] .sup.1H NMR (400 MHz, DMSO-d6) δ 8.83 (s, 1H), 7.37 (s, 1H), 7.24 (d, J = 8.8 Hz, 2H), 7.12-7.10 (m, 4H), 6.95 (d, J = 8.8 Hz, 2H), 6.90 (d, J = 8.4 Hz, 2H), 4.04 (t, J = 4.4 Hz, 2H), 3.85 (s, 3H), 3.63 (t, J = 4.8 Hz, 2H), 3.30 (s, 3H), 3.21 (s, 3H), 2.04 (s, 3H), 1.83 (d, J = 2.4 Hz, 6H), 1.72 (s, 6H). LC-MS: m/z 541.2 (M + H).sup.+ 270 XII.67  XI.12 [00618] LC-MS: m/z 454.1 (M + H).sup.+ 266 XII.68  XI.31 [00619] LC-MS: m/z 522.1 (M + H).sup.+ 231 XII.69  Int-XI [00620] .sup.1H NMR (400 MHz, DMSO-d6) δ 9.90 (s, 1H), 8.52-8.47 (m, 2H), 7.55 (s, 1H), 7.47 (d, J = 8.8 Hz, 2H), 7.34 (s, 1H), 7.20 (s, 2H), 7.03 (d, J = 8.8 Hz, 2H), 6.94- 6.91 (m, 1H), 2.05 (s, 3H), 1.84 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 475.2 (M + H).sup.+ 453 XII.70  XI.16 [00621] .sup.1H NMR (400 MHz, DMSO-d6): δ 8.79 (s, 1H), 7.54-7.52 (m, 1H), 7.44-7.42 (m, 1H), 7.28-6.98 (m, 9H), 3.85 (s, 3H), 3.80 (d, J = 2.4 Hz, 2H), 3.37 (s, 3H), 2.04 (s, 3H), 2.00- 1.96 (m, 1H), 1.83 (s, 6H), 1.72 (s, 6H), 0.97 (d, J = 6.4 Hz, 6H). 521 XII.71  XI.32 [00622] LC-MS: m/z 431.2 (M + H)+ 522 XII.72  XI.33 [00623] LC-MS: m/z 445.2 525 XII.73  VII.78 [00624] LC-MS: m/z 580.4 (M + H)+ 526 XII.74  XI.16 [00625] LC-MS: m/z 554.4 (M + H)+ 528 XII.75  XI.34 [00626] LC-MS: m/z 489.1 (M + H)+ 535 XII.76  XI.35 [00627] LC-MS: m/z 396.1 (M + H)+ 536 XII.77  VII.81 [00628] LC-MS: m/z 488.3 (M + H)+ 537 XII.78  XI.36 [00629] LC-MS: m/z 514.3 (M + H)+ 538 XII.79  XI.37 [00630] LC-MS: m/z 456.3 (M + H)+ 541 XII.80  VII.80 [00631] LC-MS: m/z 402.1 (M + H)+. 542 XII.81  XI.38 [00632] LC-MS: m/z 431.31 (M + H)+ 543 XII.82  XI.39 [00633] LC-MS: m/z 422.1 (M + H)+ 544 XII.83  XI.39 [00634] LC-MS: m/z 452.1 (M + H)+ 545 XII.84  XI.40 [00635] LC-MS: m/z 392.2 (M + H)+ 546 XII.85  XI.41 [00636] LC-MS: m/z 436.2 547 XII.86  XI.42 [00637] LC-MS: m/z 448.2 (M + H)+. 548 XII.87  XI.43 [00638] LC-MS: m/z 447.1 (M + H)+. 549 XII.88  XI.44 [00639] LC-MS: m/z 463.2 (M + H)+. 550 XII.89  XI.45 [00640] LC-MS: m/z 466.2 (M + H)+ 551 XII.90  XI.46 [00641] LC-MS: m/z 511.4 (M + H)+ 552 XII.91  XI.47 [00642] LC-MS: m/z 481.2 (M + H)+ 553 XII.92  XI.48 [00643] LC-MS: m/z 461.1 (M + H)+. 554 XII.93  XI.49 [00644] LC-MS: m/z 391.3 (M + H)+ 555 XII.94  XI.50 [00645] LC-MS: m/z 446.3 (M + H)+. 556 XII.95  XI.51 [00646] LC-MS: m/z 417.2 (M + H)+ 557 XII.96  XI.52 [00647] LC-MS: m/z 479.2 (M + H)+ 558 XII.97  XI.33 [00648] LC-MS: m/z 416.2 (M + H)+ 559 XII.98  XI.31 [00649] LC-MS: m/z 538.2 (M + H)+ 560 XII.99  XI.53 [00650] LC-MS: m/z 459.3 (M + H)+ 561 XII.100 XI.54 [00651] Proceeded with crude/TLC reference 563 XII.101 XI.55 [00652] LC-MS: m/z 444.1 (M + H)+ 564 XII.102 XI.54 [00653] LC-MS: m/z 515.15 (M + H)+. 565 XII.103 XI.56 [00654] LC-MS: m/z 475.1 (M + H)+. 566 XII.104 XI.57 [00655] LC-MS: m/z 437.2 (M + H)+ 567 XII.105 VII.88 [00656] LC-MS: m/z 391.3 (M + H)+ 568 XII.106 XI.58 [00657] LC-MS: m/z 479.2 (M + H)+ 570 XII.107 XI.59 [00658] LC-MS: m/z 449.3 (M + H)+ 571 XII.108 XI.60 [00659] LC-MS: m/z 503.2 (M + H)+ 572 XII.109 XI.61 [00660] LC-MS: m/z 449.3 (M + H)+ 573 XII.110 XI.62 [00661] LC-MS: m/z 507.1 (M + H)+ 574 XII.111 XI.63 [00662] LC-MS: m/z 459.3 (M + H)+ 575 XII.112 XI.64 [00663] LC-MS: m/z 434.1 (M + H)+ 576 XII.113 XI.65 [00664] LC-MS: m/z 431.55 (M + H)+ 577 XII.114 XI.66 [00665] LC-MS: m/z 469.25 (M − H)+ 578 XII.115 XI.67 [00666] LC-MS: m/z 446.05 (M + H)+ 579 XII.116 XI.53 [00667] LC-MS: m/z 496.05 (M + H)+ 580 XII.117 XI.53 [00668] LC-MS: m/z 512.10 (M + H)+. 581 XII.118 XI.68 [00669] LC-MS: m/z 446.65 (M + H).sup.+ 582 XII.119 XI.69 [00670] 1H NMR (400 MHz, DMSO-d6) δ 8.83 (s, 1H), 7.35 (d, J = 2.8 Hz, 1H), 7.15-7.10 (m, 6H), 7.00-6.98 (m, 2H), 6.90-6.87 (m, 2H 3.85 (s, 3H), 3.72 (s, 3H), 3.24- 3.21 (m, 5H), 2.67- 2.58 (m, 6H), 1.85- 1.74 (m, 4H) LC-MS: m/z 459.25 (M + H)+ 585 XII.120 XI.70 [00671] LC-MS: m/z 475.3 (M + H)+ 586 XII.121 XI.71 [00672] LC-MS: m/z 445.0 (M + H)+ 587 XII.122 IX.12 [00673] LC-MS: m/z 418.2 (M + H)+ 588 XII.123 XI.72 [00674] LC-MS: m/z 438.1 (M + H)+ 589 XII.124 XI.73 [00675] LC-MS: m/z 465.2 (M + H)+ 590 XII.125 XI.74 [00676] LC-MS: m/z 461.2 (M + H)+ 591 XII.126 IX.9 [00677] LC-MS: m/z 467.05 (M + H)+ 592 XII.127 XI.75 [00678] LC-MS: m/z 432.2 (M + H)+ 593 XII.128 XI.76 [00679] LC-MS: m/z 472.1 (M + H)+ 594 XII.129 VII.111 [00680] LC-MS: m/z 447.1 (M + H)+ 595 XII.130 XI.77 [00681] LC-MS: m/z 490.1 (M + H)+ 596 XII.131 XI.78 [00682] LC-MS: m/z 448.2 (M + H)+ 597 XII.132 XI.79 [00683] LC-MS: m/z 452.2 (M + H)+ 598 XII.133 VII.123 [00684] LC-MS: m/z 446.05 (M + H)+ 599 XII.134 XI.81 [00685] LC-MS: m/z 481.2 (M + H)+ 600 XII.135 XI.82 [00686] LC-MS: m/z 469.05 (M + H)+ 601 XII.136 XI.83 [00687] LC-MS: m/z 453.9 (M + H)+ 602 XII.137 VII.114 [00688] LC-MS: m/z 433.10 (M + H)+ 603 XII.138 XI.84 [00689] LC-MS: m/z 513.2 (M + H)+ 609 XII.139 XI.85 [00690] LC-MS: m/z 460.3 (M + H)+ 612 XII.140 XI.86 [00691] LC-MS: m/z 431.1 (M + H)+ 613 XII.141 XI.32 [00692] LC-MS: m/z 494.2 (M + H)+ 614 XII.142 XI.53 [00693] LC-MS: m/z 522.2 (M + H)+ 615 XII.143 XI.87 [00694] LC-MS: m/z 511.0 (M + H)+ 616 XII.144 IX.18 [00695] LC-MS: m/z 468.1 (M + H)+ 617 XII.145 XI.88 [00696] LC-MS: m/z 465.1 (M + H)+ 618 XII.146 XI.89 [00697] LC-MS: m/z 449.2 (M + H)+ 619 XII.147 XI.53 [00698] LC-MS: m/z 485.2 (M + H)+ 620 XII.148 XI.53 [00699] LC-MS: m/z 528.2 (M + H)+ 621 XII.149 XI.53 [00700] LC-MS: m/z 528.4 (M + H)+ 622 XII.150 XI.90 [00701] LC-MS: m/z 463.0 (M + H)+ 624 XII.151 XI.91 [00702] LC-MS: m/z 435.1 (M + H)+ 625 XII.152 XI.53 [00703] LC-MS: m/z 447.2 (M + H)+ 626 XII.153 XI.92 [00704] LC-MS: m/z 484.2 (M + H).sup.+ 627 XII.154 XI.53 [00705] LC-MS: m/z 526.3 (M + H).sup.+ 628 XII.155 XI.53 [00706] .sup.1H NMR (400 MHz, DMSO-d6) δ 8.90- 8.69 (s, 1H), 7.82- 7.79 (m, 1H), 7.57- 7.42 (m, 2H), 7.39- 7.35 (m, 2H), 7.14- 7.10 (m, 2H), 6.93 (s, 1H), 6.83-6.78 (m, 1H), 6.74 (d, J = 9.2 Hz, 1H), 3.92-3.89 (m, 2H), 3.87 (s, 3H), 3.22 (s, 3H), 2.47- 2.30 (m, 1H), 2.13 (s, 3H), 1.80-1.65 (m, 6H), 1.48-1.18 (m, 8H), 0.96-0.94 (m, 3H). 630 XII.156 XI.53 [00707] 1H NMR (400 MHz, DMSO-d6) δ 8.86 (s, 1H), 7.61 (d, J = 2.4 Hz, 1H), 7.15-7.07 (m, 4H), 6.95-6.90 (m, 3H), 6.79 (dd, J1 = 2.8 Hz, J2 = 8.8 Hz, 1H), 6.64 (d, J = 8.0 Hz, 1H), 3.86 (s, 3H), 3.23 (s, 3H), 2.46-2.42 (m, 1H), 2.11 (s, 3H), 1.87- 1.68 (m, 6H), 1.39- 1.30 (m, 5H), 0.87- 0.83 (m, 2H), 0.56- 0.52 (m, 2H). 631 XII.157 XI.53 [00708] 1H NMR (400 MHz, DMSO-d6) δ 8.88 (s, 1H), 7.68 (s, 1H), 7.20-7.12 (m, 4H), 6.95-6.92 (m, 3H), 6.80-6.78 (m, 1H), 6.65-6.64 (d, J = 8.4 Hz, 1H), 3.84 (s, 3H), 3.22 (s, 3H), 2.24 (s, 1H), 2.20 (s, 3H), 2.10 (s, 3H), 1.80- 1.77 (m, 6H), 1.39- 1.33 (m, 4H). 632 XII.158 XI.53 [00709] LC-MS: m/z 486.3 (M + H)+ 633 XII.159 XI.53 [00710] 1H NMR (400 MHz, DMSO-d6) δ 8.70 (s, 1H), 7.36 (d, J = 3.2 Hz, 2H), 7.13-7.10 (m, 3H), 6.93-6.91 (m, 3H), 6.75-6.73 (m, 2H), 4.05-4.00 (m, 1H), 3.86 (s, 3H), 3.56 (s, 2H), 3.22 (s, 3H), 2.12 (s, 3H), 1.79-1.68 (m, 2H), 1.30-1.16 (m, 8H), 0.99 (s, 9H). 634 XII.160 XI.53 [00711] 1H NMR (400 MHz, DMSO-d6) δ 8.67 (s, 1H), 7.35 (d, J = 2.8 Hz, 1H), 7.10 (dd, J1 = 2.4 Hz, J2 = 8.4 Hz, 3H), 7.05 (dd, J1 = 3.2 Hz, J2 = 9.2 Hz, 1H), 6.91-6.89 (m, 3H), 6.77 (dd, J1 = 2.4 Hz, J2 = 8.4 Hz, 1H), 6.71 (d, J = 9.2 Hz, 1H), 4.14- 4.10 (m, 1H), 3.83 (s, 3H), 3.20 (s, 3H), 2.45-2.35 (m, 1H), 2.10 (s, 3H), 1.86- 1.67 (m, 7H), 1.50- 1.20 (m, 13H). 635 XII.161 XI.53 [00712] LC-MS: m/z 444.2 (M − 95)+ COCF3 fragment 636 XII.162 XI.53 [00713] LC-MS: m/z 444.20 (M + H)+. 637 XII.163 XI.53 [00714] LC-MS: m/z 568.3 (M + H)+ 640 XII.164 XI.53 [00715] LC-MS: m/z 456.3 (M − H)+ 641 XII.165 XI.93 [00716] LC-MS: m/z 484.1 (M + H)+ 642 XII.166 XI.94 [00717] LC-MS: m/z 458.2 (M + H)+ 643 XII.167 XI.81 [00718] LC-MS: m/z 431.25 (M + H)+ 646 XII.168 XI.95 [00719] LC-MS: m/z 460.2 (M + H)+ 647 XII.169 XI.96 [00720] LC-MS: m/z 446.1 (M + H)+ 648 XII.170 XI.32 [00721] LC-MS: m/z 416.05 (M + H)+ 649 XII.171 VIII.7 [00722] LC-MS: m/z 443.3 (M + H)+ 650 XII.172 VII [00723] LC-MS: m/z 519.2 (M + H)+ 652 XII.173 XI.85 [00724] LC-MS: m/z 445.3 (M + H)+ 654 XII.174 XI.80 [00725] LC-MS: m/z 447.0 (M + H)+ 655 XII.175 XI.80 [00726] LC-MS: m/z 416.2 (M + H)+ 656 XII.176 XI.53 [00727] LC-MS: m/z 522.2 (M + H)+ 659 XII.177 XI.97 [00728] LC-MS: m/z 465.2 (M + H)+ 660 XII.178 XI.98 [00729] LC-MS: m/z 518.1 (M + H)+ 661 XII.179 XI.99 [00730] LC-MS: m/z 499.2 (M − H)+ 662 XII.180 XI.99 [00731] LC-MS: m/z 469.2 (M + H)+ 663 XII.181 XI.100 [00732] LC-MS: m/z 471.2 (M + H)+ 665 XII.182 XI.101 [00733] LC-MS: m/z 464.2 (M + H)+ 666 XII.183 XI.101 [00734] LC-MS: m/z 463.2 (M + H)+ 669 XII.184 XI.101 [00735] LC-MS: m/z 493.2 (M + H)+ 671 XII.185 XI.102 [00736] LC-MS: m/z 556.2 (M + H)+ 672 XII.186 XI.101 [00737] LC-MS: m/z 519.2 (M + H)+ 673 XII.187 XI.85 [00738] LC-MS: m/z 486.25 (M + H)+ 675 XII.188 XI.98 [00739] LC-MS: m/z 534.2 (M + H)+ 676 XII.189 XI.98 [00740] LC-MS: m/z 503.2 (M + H)+ 677 XII.190 XI.104 [00741] LC-MS: m/z 436.1 (M + H)+ 678 XII.191 XI.53 [00742] LC-MS: m/z 537.3 (M + H)+ 680 XII.192 XI.103 [00743] LC-MS: m/z 464.1 (M + H)+ 681 XII.193 XI.102 [00744] LC-MS: m/z 478.2 (M + H)+ 682 XII.194 XI.104 [00745] LC-MS: m/z 450.2 (M + H)+

Intermediate-XIII

[0584] ##STR00746##

Step-a: Synthesis of methyl 2-((1,4-dioxaspiro[4.5]decan-8-yl)amino)benzoate (XIIIa)

[0585] A solution of methyl anthranilate (3 g, 20 mmol, 1 eq.) and 1,4-Cyclohexanedione monoethylene acetal (4.6 g, 30 mmol, 1.5 eq.) in dichloroethane (50 mL) was added with acetic acid (20 mL) and stirred at RT for 2 h. Reaction mass was cooled to 0° C. and added with sodium triacetoxyborohydride (6.3 g, 30 mmol, 1.5 eq.) and allowed to stir at RT for 36 h. Reaction mass was added with saturated bicarbonate solution and extracted with dichloromethane, purified by combi-flash to afford title product (1.01 g, 17%).

[0586] .sup.1H NMR (400 MHz, DMSO-d6) δ 7.77 (d, J=7.6 Hz, 1H), 7.71 (d, J=7.6 Hz, 1H), 7.39-7.35 (m, 1H), 6.83 (d, J=8.8 Hz, 1H), 6.57-6.53 (m, 1H), 3.87 (s, 4H), 3.78 (s, 3H), 3.60-3.58 (m, 1H), 1.95-1.90 (m, 2H), 1.70-1.61 (m, 4H), 1.60-1.48 (m, 2H); LC-MS: m/z 292.0 (M+H).sup.+

Step-b: Synthesis of methyl 2-((4-oxocyclohexyl)amino)benzoate (XIIIb)

[0587] A solution of compound XIIIa (1.01 g, 3.4 mmol, 1 eq.) in acetone (30 mL) was added with 2N HCl (10 mL) and allowed to stir at RT overnight. Reaction mass was extracted with ethyl acetate from water and concentrated in vacuo. The crude was used further without purification.

[0588] .sup.1H NMR (400 MHz, DMSO-d6) δ 7.81 (dd, J.sub.1=0.8 Hz, J.sub.2=7.6 Hz, 1H), 7.75 (d, J=7.6 Hz, 1H), 6.94 (d, J=8.8 Hz, 1H), 6.59 (t, J=7.6 Hz, 1H), 3.97-3.95 (m, 1H), 3.79 (s, 3H), 2.57-2.53 (m, 2H), 2.29-2.19 (m, 4H), 1.77-1.72 (m, 2H); LC-MS: m/z 248.2 (M+H).sup.+

Step-c: Synthesis of methyl 2-((4-((4-((3r,5r,7r)-adamantan-1-yl)-2-chlorophenyl) amino)cyclohexyl) amino) benzoate (Intermediate-XIII)

[0589] A solution of compound XIIIb (0.5 g, 2.02 mmol, 1 eq.) and Intermediate-I (0.53 g, 2.02 mmol, 1 eq.) in acetic acid (10 mL) was added with sodium triacetoxyborohydride (1.28 g, 6.06 mmol, 3 eq.) and heated at 8° C. for 16 h. Reaction mass was extracted with ethyl acetate from sat. bicarbonate and brine and concentrated in vacuo. Crude was purified by combi-flash to afford title compound as pale pink liquid (0.67 g, 67%). LC-MS: m/z 493.3 (M+H).sup.+

[0590] The below intermediates were prepared by a procedure similar to Intermediate-XIII using appropriate reactants and reagents and in presence of suitable solvents and appropriate reaction conditions.

TABLE-US-00019 Interme- diate Re- CP No. actant Structure Analytical data 102, 103 XIII.1 Int-XI [00747] .sup.1H NMR (400 MHz, DMSO-d6) δ 7.27 (s, 1H), 7.02 (dd, J.sub.1 = 2.4 Hz, J.sub.2 = 8.8 Hz, 1H), 6.98 (d, J = 8.8 Hz, 2H), 6.85 (d, J = 8.8 Hz, 1H), 6.61 (d, J = 8.8 Hz, 2H), 5.74 (s, 1H), 4.15-4.03 (m, 2H), 3.52 (m, 1H), 3.39 (s, 1H), 2.31-2.18 (m, 3H), 2.07 (s, 3H), 1.98-1.92 (m, 1H), 1.84 (s, 6H), 1.81-1.61 (m, 9H), 1.18 (t, J = 7.2 Hz, 3H), 1.12-1.05 (m, 1H). LC-MS: m/z 507.2 (M + H).sup.+ 128, 129 XIII.2 XI.1 [00748] LC-MS: m/z 561.2 (M + H).sup.+ 130 XIII.3 Int-I.1 [00749] LC-MS: m/z 368.2 (M + H).sup.+ 131 XIII.4 Int-I.1 [00750] .sup.1H NMR (400 MHz, DMSO-d6) δ 7.02 (d, J = 8.4 Hz, 2H), 6.59 (d, J = 8.8 Hz, 2H), 5.01 (d, J = 9.6 Hz, 1H), 3.98-3.88 (m, 3H), 2.75-2.68 (m, 1H), 2.08 (s, 3H), 2.00- 1.82 (m, 1H), 1.77 (m, 8H), 1.73-1.46 (m, 4H), 1.36-1.23 (m, 2H), 1.07 (t, J = 7.6 Hz, 3H). LC- MS: m/z 382.2 (M + H).sup.+ 136 XIII.5 Int-XI [00751] LC-MS: m/z 507.3 (M + H).sup.+ 162 XIII.6 Int-XI [00752] LC-MS: m/z 608.2 (M + H).sup.+ 172 XIII.7 Int-XI [00753] LC-MS: m/z 594.2 (M + H).sup.+ 244 XIII.8 Int-I [00754] LC-MS: m/z 375.1 (M − 55).sup.+ Boc fragment 248 XIII.9 Int-I [00755] .sup.1H NMR (400 MHz, DMSO- d6) δ 7.19 (d, J = 1.9 Hz, 1H), 7.13 (d, J = 8.8 Hz, 1H), 6.76 (d, J = 8.8 Hz, 1H), 4.65-4.63 (m, 1H), 3.61-3.60 (m, 2H), 3.37- 3.36 (m, 1H), 3.15-3.08 (m, 2H), 2.02 (bs, 3H), 1.89-1.88 (m, 1H), 1.73 (s, 6H), 1.70 (s, 6H), 1.63- 1.62 (m, 2H), 1.26 (s, 9H). 244 XIII.10 XIII.8 [00756] .sup.1H NMR (400 MHz, DMSO- d6) δ 8.60 (s, 1H), 8.00 (s, 1H), 7.40 (s, 1H), 7.18 (d, J = 2.0 Hz, 1H), 7.11 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 8.8 Hz, 1H), 6.63 (d, J = 8.8 Hz, 1H), 4.60 (s, 1H), 3.97-3.89 (bs, 1H), 3.84 (s, 3H), 2.02 (s, 3H), 1.77 (s, 6H), 1.67 (s, 6H). LC-MS: m/z 480.1 (M + H).sup.+ 248 XIII.11 XIII.9 [00757] LC-MS: m/z 494.1 (M + H).sup.+ 567 XIII.12 XII.105 [00758] LC-MS: m/z 460.3 (M + H)+.

Intermediate-XIV

[0591] ##STR00759##

Step-a: Synthesis of 4-((2-(methoxycarbonyl)phenyl)amino)benzoic acid (Intermediate-XIV)

[0592] A solution of Intermediate-II.20 (3 g, 9.1 mmol, 1 eq.) in DCM (30 mL) was cooled in ice for 10 minutes. TFA (3 mL) was added drop wise and allowed to stir at RT for 16 h. Reaction mass was concentrated in vacuo. The crude was triturated with n-pentane and dried in vacuo to afford title product as pale green solid (2.0 g, 800).

[0593] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.58 (s, 1H), 9.40 (s, 1H), 7.93 (dd, J.sub.1=0.6 Hz, J.sub.2=8.0 Hz, 1H), 7.87 (dd, J.sub.1=2.0 Hz, J.sub.2=6.8 Hz, 2H), 7.52-7.46 (m, 2H), 7.26 (d, J=8.8 Hz, 2H), 7.01-6.97 (m, 1H), 3.84 (s, 3H); LC-MS: m/z 272.1 (M+H).sup.+

Alternate or General Procedure for Synthesizing the Corresponding Carboxylic Acid Compounds which are Having Methyl & Ethyl Esters

[0594] To a solution of ester (1 mmol) in THF:MeH:H.sub.2O (4+4+2 mL), LiOH.H.sub.2O (5 mmol) was added and stirred at RT for 16 h. Reaction mass was concentrated in vacuo, diluted with water and acidified with 2 N HCl to pH 5. The precipitate obtained was filtered and dried under vacuum. This solid was washed with 10% ether in hexane mixture and dried to afford desired acid.

[0595] The below intermediates were prepared by a procedure similar to Intermediate-XIV using appropriate reactants and reagents and in presence of suitable solvents and appropriate reaction conditions.

TABLE-US-00020 Interme- diate CP No. Reactant Structure Analytical data 106, 107, 145, 215 XIV.1 VII.6 [00760] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.26 (s, 1H), 8.27 (s, 1H), 7.75 (d, J = 8.8 Hz, 1H), 7.43 (s, 1H), 7.35-7.3 (m, 2H), 6.86 (d, J = 8.9 Hz, 2H), 2.06 (s, 3H), 1.86 (s, 6H), 1.73 (s, 6H). LC- MS: m/z 382.1 (M + H).sup.+ 254, 301 XIV.2 II.15 [00761] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.59 (s, 1H), 10.38 (s, 1H), 8.49 (dd, J.sub.1 = 1.9 Hz, J.sub.2 = 4.4 Hz, 1H), 8.31 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 5.8 Hz, 1H), 7.89 (m, 4H), 7.0 (m, 1H), 3.92 (s, 3H). 255 XIV.3 V.4 [00762] .sup.1H NMR (400 MHz, DMSO-d6) δ 7.9-7.8 (m, 1H), 7.80-7.70 (m, 1H), 7.64 (d, J = 9.6 Hz, 2H), 7.52-7.40 (m, 2H), 6.47 (d, J = 9.2 Hz, 2H), 3.55 (s, 3H), 3.24 (s, 3H), 1.49 (s, 9H). LC-MS: m/z 286.1 (M + H).sup.+ 258 XIV.4 V.5 [00763] .sup.1H NMR (400 MHz, DMSO-d6) δ 8.57 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 4.9 Hz, 1H), 8.01 (dd, J.sub.1 = 1.4 Hz, J.sub.2 = 7.3 Hz, 1H), 7.78 (d, J = 8.8 Hz, 2H), 7.23-7.20 (m, 3H). 259, 346 XIV.5 II.16 [00764] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.5 (s, 1H), 9.75 (s, 1H), 7.97 (d, J = 8.8 Hz, 2H), 7.85 (d, J = 8.8 Hz, 2H), 7.79 (m, 1H), 7.53 (d, J = 6.8 Hz, 1H), 7.14 (d, J = 8.3 Hz, 1H), 4.35 (m, 2H), 1.38 (t, J = 2.0 Hz, 3H). 265 XIV.6 II.18 [00765] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.64 (s, 1H), 9.29 (s, 1H), 8.11 (dd, J.sub.1 = 1.6 Hz, J.sub.2 = 8.4 Hz, 1H), 7.89 (d, J = 8.8 Hz, 2H), 7.63-7.58 (m, 1H), 7.50- 7.46 (m, 1H), 7.30 (d, J = 8.8 Hz, 2H), 7.12-7.06 (m, 1H). LC-MS: m/z 257.1 (M − H).sup.−. 293, 294, 276 XIV.7 VI.44 [00766] .sup.1H NMR (400 MHz, DMSO-d6) δ 9.23 (s, 1H), 8.68 (s, 1H), 7.89 (d, J = 6.9 Hz, 1H), 7.78 (d, J = 8.8 Hz, 2H), 7.41-7.40 (m, 1H), 7.23-7.20 (m, 4H), 7.11 (d, J = 8.3 Hz, 1H), 7.03 (d, J = 8.8 Hz, 2H), 6.76 (t, J = 7.6 Hz, 1H), 3.86 (s, 3H). 302 XIV.8 II.21 [00767] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.2 (s, 1H), 10.05 (s, 1H), 8.41-8.40 (m, 1H), 8.26 (d, J = 7.8 Hz, 2H), 7.64 (d, J = 8.3 Hz, 2H), 7.22 (d, J = 1.9 Hz, 2H), 6.92-6.89 (m, 1H), 3.90 (s, 3H), 3.52 (s, 3H). 303 XIV.9 II.22 [00768] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.4 (s, 1H), 8.92 (s, 1H), 7.82 (d, J = 8.8 Hz, 2H), 7.74 (s, 1H), 7.54-7.52 (m, 2H), 7.45-7.44 (m, 2H), 7.09 (d, J = 8.8 Hz, 2H), 3.84 (s, 3H). LC-MS: m/z 272.0 (M + H).sup.+ 315, 316 XIV.10 II.35 [00769] LC-MS: m/z 348.1 (M + H).sup.+ 330 XIV.11 II.24 [00770] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.95 (s, 1H), 8.10 (t, J = 7.8 Hz, 1H), 7.99 (d, J = 8.3 Hz, 2H), 7.88 (d, J = 7.4 Hz, 1H), 7.38 (d, J = 8.3 Hz, 1H), 7.26 (d, J = 8.3 Hz, 2H), 3.82 (s, 3H). LC-MS: m/z 274.0 (M + H).sup.+ 333, 341, 395, 408 XIV.12 II.25 [00771] .sup.1H NMR (400 MHz, DMSO-d6) δ 13.01 (s, 1H), 9.32 (s, 1H), 7.92-7.90 (m, 1H), 7.77-7.76 (m, 1H), 7.62-7.60 (m, 1H), 7.48- 7.44 (m, 3H), 7.28-7.24 (m, 1H), 6.90-6.86 (m, 1H), 3.89 (s, 3H). LC-MS: m/z 272.1 (M + H).sup.+ 334 XIV.13 II.26 [00772] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.79 (s, 1H), 7.93-7.90 (m, 3H), 7.71-7.67 (m, 1H), 7.40 (t, J = 7.6 Hz, 1H), 7.23 (d, J = 8.0 Hz, 1H), 6.93 (d, J = 8.8 Hz, 2H), 3.67 (s, 3H). LC-MS: m/z 273.1 (M + H).sup.+ 353 XIV.14 V.7 [00773] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.80 (s, 1H), 7.78 (d, J = 7.2 Hz, 1H), 7.67 (t, J = 7.6 Hz, 1H), 7.42-7.37 (m, 2H), 7.27-7.21 (m, 2H), 7.07 (s, 1H), 6.77 (d, J = 7.2 Hz, 1H), 3.50 (s, 3H), 3.22 (s, 3H). LC-MS: m/z 284.1 (M + H).sup.+ 357 XIV.15 V.9 [00774] LC-MS: m/z 391.2 (M + H).sup.+ 394 XIV.16 II.34 [00775] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.97 (s, 1H), 8.45 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 4.8 Hz, 1H), 8.34 (t, J = 2.0 Hz, 1H), 8.28 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 8.0 Hz, 1H), 7.92-7.90 (m, 1H), 7.62-7.59 (m, 1H), 7.45 (t, J = 8.0 Hz, 1H), 6.94 (dd, J.sub.1 = 4.8 Hz, J.sub.2 = 7.6 Hz, 1H), 3.91 (s, 3H). LC-MS: m/z 273.1 (M + H).sup.+ 363 XIV.17 II.33 [00776] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.81 (s, 1H), 8.25 (s, 1H), 7.60 (s, 1H), 7.33-7.21 (m, 5H), 7.04 (d, J = 8.4 Hz, 2H), 2.04 (s, 3H), 1.84 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 348.1 (M + H).sup.+ 386, 387 XIV.18 VI.62 [00777] .sup.1H NMR (400 MHz, DMSO-d6) δ 10.02 (s, 1H), 8.64 (s, 1H), 8.39-8.38 (m, 1H), 8.26-8.24 (m, 1H), 7.76 (d, J = 6.8 Hz, 2H), 7.66-7.63 (m, 2H), 7.18-7.15 (m, 2H), 6.99-6.97 (m, 2H), 6.86 (dd, J.sub.1 = 4.8 Hz, J.sub.2 = 8.0 Hz, 1H), 3.90 (s, 3H). LC-MS: m/z 364.2 (M + H).sup.+ 638 XIV.19 II.29 [00778] LC-MS: m/z 296.2 (M + H)+ 651 XIV.20 II.28 [00779] LC-MS: m/z 310.05 (M + H)+

Intermediate-XV

[0596] ##STR00780##

Step-a: Synthesis of methyl 2-(4-(4-((3R,5S)-adamantan-1-yl)phenyl)carbamoyl) phenyl) amino)benzoate (Intermediate-XV)

[0597] A solution of compound-XIV (0.2 g, 0.74 mmol, 1 eq.) and Intermediate-I.1 (0.185 g, 0.81 mmol, 1.1 eq.) was cooled in ice. HATU (0.34 g, 0.89 mmol, 1.2 eq.) followed by DIPEA (0.39 mL, 2.22 mmol, 3 eq.) were added and allowed to stir at RT for 16 h. Reaction mass was added to ice water slowly under stirring. The obtained precipitate was filtered, washed with cold water twice followed by n-pentane twice and dried in vacuo to afford title compound as cream coloured solid (0.35 g, 98%).

[0598] .sup.1H NM/R (400 MHz, DMSO-d6) δ 10.01 (s, 1H), 9.43 (s, 1H), 7.96-7.91 (m, 3H), 7.69 (d, J=8.4 Hz, 2H), 7.54-7.49 (m, 1H), 7.45 (d, J=8.0 Hz, 1H), 7.34-7.31 (m, 4H), 6.95 (t, J=6.8 Hz, 1H), 3.86 (s, 3H), 2.06 (s, 3H), 1.87 (s, 6H), 1.74 (s, 6H); LC-MS: m/z 481.1 (M+H).sup.+

[0599] The below intermediates were prepared by a procedure similar to Intermediate-XV using appropriate reactants and reagents and in presence of suitable solvents and appropriate reaction conditions.

TABLE-US-00021 Interme- diate CP No. Reactant Structure Analytical data 71 XV.1 Int-XIV & I.4 [00781] LC-MS: m/z 560.1 (M + H).sup.+ 106 XV.2 XIV.1 [00782] .sup.1H NMR (400 MHz, DMSO- d6) δ 8.03 (s, 1H), 7.47-7.4 (m, 3H), 7.33-7.27 (m, 2H), 6.9 (d, J = 8.3 Hz, 2H), 4.46- 4.44 (m, 1H), 3.64-3.61 (m, 5H), 2.32 (m, 1H), 2.05 (s, 3H), 1.85 (s, 9H), 1.73 (s, 6H). LC-MS: m/z 493.2 (M + H).sup.+ 107 XV.3 XIV.1 [00783] .sup.1H NMR (400 MHz, DMSO- d6) δ 8.03 (s, 1H), 7.47-7.4 (m, 3H), 7.33-7.27 (m, 2H), 6.9 (d, J = 8.3 Hz, 2H), 4.46- 4.44 (m, 1H), 3.64-3.61 (m, 5H), 2.32 (m, 1H), 2.05 (s, 3H), 1.85 (s, 9H), 1.73 (s, 6H). LC-MS: m/z 493.2 (M + H).sup.+ 109 XV.4 Int-XI [00784] LC-MS: m/z 584.2 (M + H).sup.+ 145 XV.5 XIV.1 [00785] .sup.1H NMR (400 MHz, DMSO- d6) δ 7.99 (s, 1H), 7.85 (d, J = 7.8 Hz, 1H), 7.65 (d, J = 8.8 Hz, 2H), 7.39 (s, 1H), 7.29-7.28 (m, 2H), 6.90 (d, J = 8.8 Hz, 2H), 4.60-4.58 (m, 1H), 3.91-3.87 (m, 2H), 3.02-2.98 (m, 1H), 2.05 (s, 3H), 1.97-1.76 (m, 10H), 1.72 (s, 6H), 1.40-1.30 (m, 2H), 0.88 (t, J = 7.2 Hz, 3H). LC-MS: m/z 521.1 (M + H).sup.+ 161 XV.6 I.16 [00786] LC-MS: m/z 381 (M + H).sup.+ 186 XV.7 Int-XI [00787] LC-MS: m/z 539.1 (M + H).sup.+ 212 XV.8 XI.1 [00788] .sup.1H NMR (400 MHz, DMSO- d6) δ 10.36 (s, 1H), 8.15 (s, 1H), 7.55 (s, 1H), 7.43 (d, J = 1.2 Hz, 2H), 7.31 (d, J = 0.8 Hz, 2H), 6.94 (s, 1H), 4.88 (d, J = 5.2 Hz, 1H), 4.76 (d, J = 5.2 Hz, 1H), 3.71 (s, 3H), 2.06 (s, 3H), 1.86 (s, 6H), 1.73 (s, 6H), 1.42 (d, J = 3.2 Hz, 6H), LC-MS: m/z 607.2 (M + H).sup.+ 215 XV.9 XIV.1 [00789] LC-MS: m/z 507.3 (M + H).sup.+ 230 XV.10 Int-XI [00790] LC-MS: m/z 536.3 (M + H).sup.+ 254 XV.11 XIV.2 [00791] .sup.1H NMR (400 MHz, DMSO- d6) δ δ 10.35 (s, 1H), 10.02 (s, 1H), 8.51 (dd, J.sub.1 = 2.0 Hz, J2 = 4.5 Hz, 1H), 8.31 (dd, J1 = 2.0 Hz, J.sub.2 = 7.8 Hz, 1H), 7.96 (d, J = 8.8 Hz, 2H), 7.89 (d, J = 8.8 Hz, 2H), 7.69 (d, J = 8.3 Hz, 2H), 7.32 (d, J = 8.8 Hz, 2H), 6.99 (m, 1H), 3.92 (s, 3H), 2.06 (s, 3H), 1.82 (s, 6H), 1.74 (s, 6H). 255 XV.12 XIV.3 [00792] .sup.1H NMR (400 MHz, DMSO- d6) δ 9.79 (s, 1H), 7.84 (dd, J1 = 1.2 Hz, J2 = 7.6 Hz, 1H), 7.77 (d, J = 8.8 Hz, 2H), 7.73-7.69 (m, 1H), 7.65 (d, J = 8.8 Hz, 2H), 7.48-7.40 (m, 2H), 7.28 (d, J = 8.8 Hz, 2H), 6.53 (d, J = 8.8 Hz, 2H), 3.57 (s, 3H), 3.27 (s, 3H), 2.05 (s, 3H), 1.85 (s, 6H), 1.73 (s, 6H), LC-MS: m/z 495.1 (M + H).sup.+ 258 XV.13 XIV.4 [00793] .sup.1H NMR (400 MHz, DMSO- d6) δ δ 9.98 (s, 1H), 8.5 (m, 1H), 7.97 (d, J = 7.3 Hz, 1H), 7.87 (d, J = 8.3 Hz, 2H), 7.68 (d, J = 8.3 Hz, 2H), 7.3 (d, J = 8.8 Hz, 2H), 7.18-7 (m, 1H), 6.98 (d, J = 8.8 Hz, 2H), 3.48 (s, 3H), 3.32 (s, 3H), 2.05 (s, 3H), 1.83 (s, 6H), 1.73 (s, 6H). 259 XV.14 XIV.5 [00794] .sup.1H NMR (400 MHz, DMSO- d6) δ δ 9.99 (s, 1H), 9.7 (s, 1H), 8.01 (d, J = 9.3 Hz, 2H), 7.93 (d, J = 8.8 Hz, 2H), 7.81 (m, 1H), 7.69 (d, J = 8.8 Hz, 2H), 7.52 (d, J = 6.8 Hz, 1H), 7.31 (d, J = 8.8 Hz, 2H), 7.13 (d, J = 8.3 Hz, 1H), 4.35 (m, 2H), 2.06 (s, 3H), 1.87 (s, 6H), 1.74 (s, 6H), 1.38 (t, J = 7.4 Hz, 3H). 272 XV.15 XI.13 [00795] .sup.1H NMR (400 MHz, DMSO- d6) δ δ 10.17 (s, 1H), 9.28 (s, 1H), 7.91-7.88 (m, 3H), 7.78 (d, J = 8.8 Hz, 2H), 7.51 (d, J = 8.4 Hz, 2H), 7.42- 7.38 (m, 1H), 7.24 (d, J = 8.8 Hz, 2H), 7.14 (d, J = 8.0 Hz, 1H), 6.66-6.65 (m, 1H), 3.86 (s, 3H), 2.08 (s, 3H), 1.90 (s, 6H), 1.76 (s, 6H). LC-MS: m/z 479.0 (M − H).sup.−. 274 XV.16 Int-XIV [00796] .sup.1H NMR (400 MHz, DMSO- d6) δ 9.34 (s, 1H), 7.92 (dd, J.sub.1 = 1.5 Hz, J.sub.2 = 7.8 Hz, 1H), 7.46 (t, J = 1.5 Hz, 1H), 7.30-7.20 (m, 5H), 6.90-6.86 (m, 1H), 3.89 (s, 3H), 3.40- 3.30 (m, 4H), 1.52-1.49 (m, 4H), 1.12-1.08 (m, 4H), 0.84-0.78 (m, 6H). 285 XV.17 Int-XIV [00797] .sup.1H NMR (400 MHz, DMSO- d6) δ δ 9.38 (s, 1H), 7.92 (d, J = 6.8 Hz, 1H), 7.78 (d, J = 8.0 Hz, 2H), 7.50-7.43 (m, 2H), 7.37 (d, J = 8.0 Hz, 1H), 7.27-7.23 (m, 2H), 6.91 (t, J = 7.6 Hz, 1H), 3.85 (s, 3H), 2.07 (s, 9H), 1.66 (s, 6H), 1.66 (s, 6H). LC-MS: m/z 405.1 (M + H).sup.+ 288 XV.18 Int-XIV [00798] .sup.1H NMR (400 MHz, DMSO- d6) δ 9.78 (s, 1H), 9.42 (s, 1H), 7.92 (d, J = 6.8 Hz, 3H), 7.52-7.50 (m, 3H), 7.44 (d, J = 7.3 Hz, 1H), 7.31 (d, J = 8.8 Hz, 2H), 6.94 (t, J = 6.8 Hz, 1H), 6.63 (d, J = 9.3 Hz, 2H), 3.86 (s, 3H), 3.23 (t, J = 7.2 Hz, 4H), 1.50-1.45 (m, 4H), 1.34-1.30 (m, 4H), 0.89 (t, J = 7.2 Hz, 6H). 293, 276 XV.19 XIV.7 [00799] .sup.1H NMR (400 MHz, DMSO- d6) δ 9.20 (s, 1H), 8.38 (s, 1H), 7.88 (dd, J.sub.1 = 1.4 Hz, J.sub.2 = 7.8 Hz, 1H), 7.37-7.36 (m, 1H), 7.19-7.16 (m, 6H), 7.05-7.04 (m, 3H), 6.75- 6.71 (m, 1H), 3.85 (s, 3H), 3.32-3.30 (m, 4H), 1.52-1.49 (m, 4H), 1.23-1.22 (m, 4H), 0.85-0.84 (m, 6H). 294 XV.20 XIV.7 [00800] .sup.1H NMR (400 MHz, DMSO- d6) δ 9.21 (s, 1H), 8.47 (s, 1H), 7.89-7.87 (dd, J1 = 1.6 Hz, J2 = 7.6 Hz, 1H), 7.68 (d, J = 8.8 Hz, 2H), 7.36 (t, J = 8.4 Hz, 1H), 7.24 (s, 1H), 7.21-7.14 (m, 4H), 7.06 (d, J = 8.0 Hz, 1H), 7.0 (d, J = 8.8 Hz, 2H), 6.74 (t, J = 7.6 Hz, 1H), 3.86 (s, 3H), 2.06 (s, 9H), 1.65 (s, 6H). LC- MS: m/z 496.0 (M + H).sup.+ 297 XV.21 VII.14 [00801] .sup.1H NMR (400 MHz, DMSO- d6) δ 10.09 (s, 1H), 9.29 (s, 1H), 7.90 (d, J = 8.3 Hz, 2H), 7.83 (d, J = 6.3 Hz, 2H), 7.72-7.7 (m, 3H), 7.51 (d, J = 8.3 Hz, 2H), 7.40 (d, J = 7.3 Hz, 1H), 7.03 (d, J = 8.3 Hz, 1H), 4.35-4.34 (m, 2H), 2.08 (s, 3H), 1.93 (s, 6H), 1.76 (s, 6H), 1.37 (t, J = 7.4 Hz, 3H). 301 XV.22 XIV.2 [00802] LC-MS: m/z 516.0 (M + H).sup.+ 302 XV.23 XIV.8 [00803] .sup.1H NMR (400 MHz, DMSO- d6) δ 10.05 (s, 1H), 10.03 (s, 1H), 8.41-8.40 (m, 1H), 8.26-8.25 (m, 1H), 7.65 (d, J = 8.3 Hz, 2H), 7.52 (d, J = 8.8 Hz, 2H), 7.27-7.26 (m, 4H), 6.88-6.87 (m, 1H), 3.89 (s, 3H), 3.57 (s, 2H), 2.04 (s, 3H), 1.82 (s, 6H), 1.72 (s, 6H). 303 XV.24 XIV.9 [00804] .sup.1H NMR (400 MHz, DMSO- d6) δ 9.92 (s, 1H), 8.85 (s, 1H), 7.89 (d, J = 8.0 Hz, 2H), 7.75 (s, 1H), 7.68 (d, J = 8.8 Hz, 2H), 7.51-7.43 (m, 3H), 7.30 (d, J = 8.8 Hz, 2H), 7.15 (d, J = 8.8 Hz, 2H), 3.85 (s, 3H), 2.06 (s, 3H), 1.86 (s, 6H), 1.74 (s, 6H). LC-MS: m/z 481.3 (M + H).sup.+ 313 XV.25 Int-XIV [00805] .sup.1H NMR (400 MHz, DMSO- d6) δ 10.04 (s, 1H), 9.43 (s, 1H), 7.96-7.94 (m, 3H), 7.72 (d, J = 8.8 Hz, 2H), 7.51 (m, 1H), 7.46 (d, J = 7.3 Hz, 1H), 7.34 (d, J = 8.3 Hz, 2H), 7.20 (t, J = 7.4 Hz, 2H), 7.05 (d, J = 8.8 Hz, 2H), 7.93 (t, J = 6.9 Hz, 1H), 6.82 (m, 3H), 3.86 (s, 3H), 3.65 (t, J = 7.3 Hz, 2H), 1.56-1.55 (m, 2H), 1.37-1.36 (m, 2H), 0.88 (t, J = 3.9 Hz, 3H). 315 XV.26 XIV.10 [00806] .sup.1H NMR (400 MHz, DMSO- d6) δ 11.53 (s, 1H), 8.66 (d, J = 7.4 Hz, 2H), 8.03 (d, J = 6.8 Hz, 1H), 7.82 (d, J = 8.8 Hz, 2H), 7.66-7.65 (m, 1H), 7.32 (d, J = 8.8 Hz, 2H), 7.21-7.10 (m, 5H), 3.91 (s, 3H), 2.06 (s, 3H), 1.89 (s, 6H), 1.71 (s, 6H). 316 XV.27 XIV.10 [00807] .sup.1H NMR (400 MHz, DMSO- d6) δ 10.13 (s, 1H), 8.56 (s, 1H), 8.45 (s, 1H), 8.07 (d, J = 7.8 Hz, 1H), 7.88 (d, J = 8.3 Hz, 2H), 7.66 (d, J = 13 Hz, 1H), 7.47 (t, J = 7.9 Hz, 1H), 7.31 (d, J = 8.3 Hz, 2H), 7.14 (d, J = 8.8 Hz, 2H), 7.08 (d, J = 8.3 Hz, 2H), 3.87 (s, 3H), 2.06 (s, 3H), 1.82 (s, 6H), 1.74 (s, 6H). 324 XV.28 XIV.5 [00808] .sup.1H NMR (400 MHz, DMSO- d6) δ 9.47 (s, 1H), 7.75-7.67 (m, 2H), 7.45 (d, J = 7.6 Hz, 1H), 7.26 (d, J = 8.4 Hz, 2H), 7.18 (d, J = 8.4 Hz, 2H), 7.09-7.02 (m, 3H), 6.47 (d, J = 8.8 Hz, 1H), 4.30 (q, J = 6.8 Hz, 2H), 3.33 (s, 3H), 2.01 (s, 3H), 1.8-0 (s, 6H), 1.70 (s, 6H), 1.32 (t, J = 6.8 Hz, 3H). LC-MS: m/z 510.3 (M + H).sup.+ 329 XV.29 Int-XIV [00809] .sup.1H NMR (400 MHz, DMSO- d6) δ 10.17 (s, 1H), 9.45 (s, 1H), 7.99-7.93 (m, 3H), 7.83 (d, J = 8.4 Hz, 2H), 7.52- 7.40 (m, 3H), 7.36-7.34 (m, 3H), 7.26-7.21 (m, 3H), 7.13 (d, J = 6.8 Hz, 1H), 7.00- 6.90 (m, 1H), 3.87 (s, 3H), 3.10-3.00 (m, 1H), 1.13 (d, J = 6.8 Hz, 6H). LC-MS: m/z 465.1 (M + H).sup.+ 330 XV.30 XIV.11 [00810] .sup.1H NMR (400 MHz, DMSO- d6) δ 10.20 (s, 1H), 8.12- 8.08 (m, 1H), 8.02 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 6.8 Hz, 2H), 7.88 (dd, J.sub.1 = 4.0 Hz, J.sub.2 = 8.0 Hz, 1H), 7.70 (d, J = 8.0 Hz, 2H), 7.40-7.37 (m, 1H), 7.33 (dd, J.sub.1 = 0.8 Hz, J.sub.2 = 2.0 Hz, 4H), 3.82 (s, 3H), 2.06 (s, 3H), 1.87 (s, 6H), 1.74 (s, 6H). LC-MS: m/z 483.1 (M + H).sup.+ 333 XV.31 XIV.13 [00811] .sup.1H NMR (400 MHz, DMSO- d6) δ 10.15 (s, 1H), 9.40 (s, 1H), 7.92 (d, J = 8.0 Hz, 1H), 7.79 (s, 1H), 7.69-7.62 (m, 3H), 7.50-7.46 (m, 3H), 7.33-7.29 (m, 3H), 6.90-6.80 (m, 1H), 3.87 (s, 3H), 2.06 (s, 3H), 1.86 (s, 6H), 1.74 (s, 6H). LC-MS: m/z 481.2 (M + H).sup.+ 334 XV.32 XIV.14 [00812] .sup.1H NMR (400 MHz, DMSO- d6) δ 10.08 (s, 1H), 7.96 (d, J = 8.3 Hz, 2H), 7.91 (d, J = 6.8 Hz, 1H), 7.68-7.66 (m, 3H), 7.40-7.37 (m, 1H), 7.32 (d, J = 8.8 Hz, 2H), 7.20 (d, J = 7.8 Hz, 1H), 6.98 (d, J = 8.3 Hz, 2H), 3.70 (s, 3H), 2.06 (s, 3H), 1.86 (s, 6H), 1.74 (s, 6H). LC-MS: m/z 482.3 (M + H).sup.+ 335 XV.33 Int-XIV [00813] .sup.1H NMR (400 MHz, DMSO- d6) δ 10.0 (s, 1H), 9.43 (s, 1H), 7.96-7.92 (m, 3H), 7.68 (d, J = 8.8 Hz, 2H), 7.51- 7.49 (m, 1H), 7.44 (d, J = 8.4 Hz, 1H), 7.33-7.29 (m, 4H), 6.95 (t, J = 7.6 Hz, 1H), 3.86 (s, 3H), 2.14 (m, 1H), 1.69 (s, 2H), 1.53-1.33 (m, 8H), 1.19 (s, 2H), 0.86 (s, 6H). LC-MS: m/z 509.3 (M + H).sup.+ 336 XV.34 XIV.10 [00814] LC-MS: m/z 482.2 (M + H).sup.+ 341 XV.35 XIV.13 [00815] .sup.1H NMR (400 MHz, DMSO- d6) δ 10.14 (s, 1H), 9.40 (s, 1H), 7.92 (d, J = 8.0 Hz, 1H), 7.80 (s, 1H), 7.68 (d, J = 8.0 Hz, 2H), 7.64 (d, J = 7.2 Hz, 1H), 7.51-7.44 (m, 3H), 7.32-7.30 (m, 3H), 6.87 (t, J = 8.0 Hz, 1H), 3.87 (s, 3H), 2.14 (s, 1H), 1.68 (s, 2H), 1.53-1.33 (m, 8H), 1.19 (s, 2H), 0.86 (s, 6H). LC-MS: m/z 509.3 (M + H).sup.+ 343 XV.36 XIV.13 [00816] .sup.1H NMR (400 MHz, DMSO- d6) δ 10.32 (s, 1H), 9.42 (s, 1H), 7.93 (d, J = 8.0 Hz, 1H), 7.84-7.82 (m, 3H), 7.66 (d, J = 6.8 Hz, 1H), 7.54- 7.12 (m, 10H), 6.88 (t, J = 7.20 Hz, 1H), 3.87 (s, 3H), 2.04-2.01 (m, 1H), 1.12 (d, J = 6.8 Hz, 6H). LC-MS: m/z 465.1 (M + H).sup.+ 344 XV.37 Int-I.1 [00817] .sup.1H NMR (400 MHz, DMSO- d6) δ 11.64 (s, 1H), 10.36 (s, 1H), 8.53 (dd, J.sub.1 = 0.8 Hz, J.sub.2 = 8.4 Hz, 1H), 8.14-8.08 (m, 4H), 8.03 (dd, J.sub.1 = 1.6 Hz, J.sub.2 = 8.0 Hz, 1H), 7.73- 7.71 (m, 3H), 7.36-7.34 (m, 2H), 7.30-7.25 (m, 1H), 3.90 (s, 3H), 2.07 (s, 3H), 1.87 (d, J = 2.4 Hz, 6H), 1.74 (s, 6H). LC-MS: m/z 509.3 (M + H).sup.+ 346 XV.38 XIV.5 [00818] .sup.1H NMR (400 MHz, DMSO- d6) δ 9.94 (s, 1H), 9.70 (s, 1H), 8.00 (d, J = 8.8 Hz, 2H), 7.93 (d, J = 8.8 Hz, 2H), 7.79 (t, J = 7.6 Hz, 1H), 7.69 (d, J = 8.8 Hz, 2H), 7.51 (d, J = 7.6 Hz, 1H), 7.30 (d, J = 8.8 Hz, 2H), 7.13 (d, J = 8.0 Hz, 1H), 4.38-4.33 (m, 2H), 2.14 (m, 1H), 1.69 (s, 2H), 1.53-1.33 (m, 11H), 1.19 (s, 2H), 0.86 (s, 6H). LC-MS: m/z 524.3 (M + H).sup.+ 353 XV.39 XIV.15 [00819] LC-MS: m/z 495.1 (M + H).sup.+ 363 XV.40 XIV.18 [00820] .sup.1H NMR (400 MHz, DMSO- d6) δ 11.61 (s, 1H), 8.61 (d, J = 8.4 Hz, 1H), 8.38 (s, 1H), 8.02 (d, J = 7.2 Hz, 1H), 7.70-7.63 (m, 2H), 7.42-7.22 (m, 6H), 7.11 (d, J = 8.8 Hz, 2H), 3.90 (s, 3H), 2.05 (s, 3H), 1.85 (s, 6H), 1.73 (s, 6H). LC-MS: m/z 481.2 (M + H).sup.+ 364 XV.41 XIV.18 [00821] .sup.1H NMR (400 MHz, DMSO- 10.39 (s, 1H), 8.46 (t, J = 2.0 Hz, 1H), 8.29 (s, 1H), 8.04 (dd, J.sub.1 = 0.8 Hz, J.sub.2 = 8.0 Hz, 1H), 7.69-7.67 (m, 1H), 7.59 (s, 1H), 7.49 (t, J = 8.0 Hz, 1H), 7.36-7.20 (m, 5H), 7.08 (d, J = 8.8 Hz, 2H), 3.87 (s, 3H), 2.05 (s, 3H), 1.84 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 481.2 (M + H).sup.+ 368 XV.42 [00822] LC-MS: m/z 523.3 (M + H).sup.+ 369 XV.43 [00823] LC-MS: m/z 509.2 (M + H).sup.+ 386 XV.44 XIV.19 [00824] .sup.1H NMR (400 MHz, DMSO- d6) δ 9.97 (s, 1H), 8.38 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 4.8 Hz, 1H), 8.33 (s, 1H), 8.24 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 8.0 Hz, 1H), 7.60 (d, J = 8.8 Hz, 2H), 7.19 (d, J = 8.8 Hz, 2H), 7.13 (d, J = 3.2 Hz, 2H), 6.99 (d, J = 8.8 Hz, 2H), 6.84 (dd, J.sub.1 = 2.8 Hz, J.sub.2 = 8.0 Hz, 1H), 3.90 (s, 3H), 3.29 (s, 6H), 1.54-1.47 (m, 4H), 1.23-1.20 (m, 4H), 0.85 (s, 6H). LC-MS: m/z 475.3 (M + H).sup.+ 387 XV.45 XIV.19 [00825] .sup.1H NMR (400 MHz, DMSO- d6) δ 9.97 (s, 1H), 8.39-8.38 (m, 2H), 8.24 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 8.0 Hz, 1H), 7.64 (dd, J.sub.1 = 8.4 Hz, J.sub.2 = 19.2 Hz, 4H), 7.21 (s, 1H), 7.12 (d, J = 8.8 Hz, 2H), 6.96 (d, J = 8.8 Hz, 2H), 6.84 (dd, J.sub.1 = 4.8 Hz, J.sub.2 = 8.0 Hz, 1H), 3.90 (s, 3H), 1.99 (s, 10H), 1.65 (s, 6H). LC-MS: m/z 497.3 (M + H).sup.+ 394 XV.46 XIV.17 & I.3 [00826] LC-MS: m/z 544.3 (M + H).sup.+ 407 XV.47 Int-XIV & I.29 [00827] .sup.1H NMR (400 MHz, DMSO- d6) δ 9.41 (s, 1H), 8.89 (t, J = 6.0 Hz, 1H), 7.93-7.91 (m, 1H), 7.87 (d, J = 8.8 Hz, 2H), 7.51-7.48 (m, 1H), 7.43-7.40 (m, 1H), 7.33-7.22 (m, 6H), 6.95-6.91 (m, 1H), 4.43 (d, J = 6.0 Hz, 2H), 3.84 (s, 3H), 2.05 (s, 3H), 1.84 (s, 6H), 1.73 (s, 6H), LC-MS: m/z 495.3 (M + H).sup.+ 408 XV.48 XIV.13 & I.29 [00828] .sup.1H NMR (400 MHz, DMSO- d6) δ 9.39 (s, 1H), 9.02 (t, J = 6.0 Hz, 1H), 7.95-7.90 (m, 1H), 7.76 (s, 1H), 7.60- 7.55 (m, 1H), 7.45-7.42 (m, 3H), 7.32-7.23 (m, 5H), 6.87-6.83 (m, 1H), 4.42 (d, J = 6.0 Hz, 2H), 3.86 (s, 3H), 2.04 (s, 3H), 1.84 (s, 6H), 1.76 (s, 6H), LC-MS: m/z 495.3 (M + H).sup.+ 638 XV.49 XIV.20 [00829] LC-MS: m/z 429.2 (M + H)+ 651 XV.50 XIV.21 [00830] LC-MS: m/z 443.2 (M + H)+ 664 XV.51 XIV.13 [00831] LC-MS: m/z 429.1 (M + H)+

Intermediate-XVI

[0600] ##STR00832##

Step-a: Synthesis of N-(4-(N-(4-((3r,5r,7r)-adamantan-1-yl) phenyl)sulfamoyl)phenyl) acetamide (Intermediate-XVI)

[0601] A solution of Intermediate-I.1 (0.5 g, 2.2 mmol) in dichloromethane (10 mL) was cooled to ° C. and added with triethylamine (0.66 g, 6.6 mmol, 3 eq.) followed by 4-acetamidobenzenesulfonyl chloride (0.51 g, 2.2 mmol) and stirred at RT for 3 h. Reaction mass was concentrated in vacuo and added with cold water. The obtained solid was filtered and dried under vacuum to afford title product (0.88 g, 94%). LC-MS: m/z 425.1 (M+H).sup.+

[0602] The below intermediates were prepared by a procedure similar to Intermediate-XVI using appropriate reactants and reagents and in presence of suitable solvents and appropriate reaction conditions.

TABLE-US-00022 Inter- mediate CP No. Reactant Structure Analytical data 372 XVI.1 Int-I.1 [00833] LC-MS: m/z 411.1 (M − H).sup.− 393, 392 XVI.2 Int-I [00834] .sup.1H NMR (400 MHz, DMSO-d6) δ 9.73 (s, 1H), 8.80 (dd, J = 1.6 Hz, J.sub.2 = 6.4 Hz, 1H), 8.31- 8.30 (m, 1H), 7.71 (d, J = 8.8 Hz, 2H), 7.63 (d, J = 9.2 Hz, 2H), 7.29 (d, J = 2.8 Hz, 1H), 7.26-7.24 (m, 1H), 7.13 (d, J = 8.8 Hz, 1H), 2.08 (s, 3H), 2.04 (s, 3H), 1.78 (s, 6H), 1.66 (s, 6H). LC-MS: m/z 459.1 (M + H).sup.+ 396 & 397 XVI.3 Int-I [00835] .sup.1H NMR (400 MHz, DMSO-d6) δ 10.32 (s, 1H), 9.76 (s, 1H), 7.71 (d, J = 8.8 Hz, 2H), 7.62 (d, J = 8.8 Hz, 2H), 7.29 (d, J = 2.0 Hz, 1H), 7.24 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 8.4 Hz, 1H), 7.13 (d, J = 8.4 Hz, 1H), 2.11-2.09 (m, 1H), 2.07 (s, 3H), 1.62 (s, 2H), 1.45-1.29 (m, 8H), 1.15 (s, 1H), 0.83 (s, 6H). LC- MS: m/z 485.1 (M + H).sup.+ 342 XVI.4 [00836] [00837] .sup.1H NMR (400 MHz, DMSO-d6) δ 10.4 (s, 1H), 7.84 (d, J = 8.3 Hz, 1H), 7.78 (d, J = 8.3 Hz, 2H), 7.7 (d, J = 8.3 Hz, 2H), 7.56 (t, J = 7.6 Hz, 1H), 7.43 (d, J = 8.0 Hz, 1H), 7.22 (t, J = 7.6 Hz, 1H), 3.8 (s, 3H). LC-MS: m/z 371.95 (M + H).sup.+2.

Intermediate-XVII

[0603] ##STR00838##

Step-a: Synthesis of N-(4-((3r,5r,7r)-adamantan-1-yl)phenyl)-4-aminobenzenesulfonamide (Intermediate-XVII)

[0604] This compound was prepared from Intermediate-XVI (0.85 g, 2 mmol, 1 eq.) by a procedure similar to the one described for Intermediate-I from Ib to afford title product as a white solid (0.75 g, 98%).

[0605] .sup.1H NMR (400 MHz, DMSO-d6) δ 9.73 (s, 1H), 7.38 (d, J=8.8 Hz, 2H), 7.17 (d, J=8.8 Hz, 2H), 6.98 (d, J=8.8 Hz, 2H), 6.52 (d, J=8.8 Hz, 2H), 5.93 (s, 2H), 2.01 (s, 3H), 1.77 (s, 6H), 1.69 (s, 6H); LC-MS: m/z 383.0 (M+H).sup.+

[0606] The below intermediates were prepared by a procedure similar to Intermediate-XVII using appropriate reactants and reagents and in presence of suitable solvents and appropriate reaction conditions.

TABLE-US-00023 Inter- mediate CP No. Reactant Structure Analytical data 372 XVII.1 XVI.1 [00839] LC-MS: m/z 383.1 (M + H).sup.+ 392, 393 XVII.2 XVI.2 [00840] .sup.1H NMR (400 MHz, DMSO- d6) δ 9.31 (s, 1H), 7.38-7.32 (m, 2H), 7.28 (d, J = 2.0 Hz, 1H), 7.24-7.22 (m, 1H), 7.15 (d, J = 8.8 Hz, 1H), 6.55-6.52 (m, 2H), 5.98 (s, 2H), 2.02 (s, 3H), 1.79 (s, 6H), 1.69 (s, 6H). LC-MS: m/z 417.1 (M + H).sup.+ 396, 397 XVII.3 XVI.3 [00841] .sup.1H NMR (400 MHz, DMSO- d6) δ 9.26 (s, 1H), 7.33 (d, J = 8.4 Hz, 2H), 7.27 (s, 1H), 7.22 (d, J = 8.8 Hz, 1H), 7.15 (d, J = 8.4 Hz, 1H), 6.53 (d, J = 8.4 Hz, 2H), 5.96 (s, 2H), 2.1 (m, 1H), 1.61 (s, 2H), 1.45-1.29 (m, 8H), 1.15 (s, 2H), 0.83 (s, 6H). LC-MS: m/z 445.1 (M + H).sup.+

Intermediate-XVIII

[0607] ##STR00842##

Step-a: Synthesis of methyl 2-(4-(N-(4-((3R,5R)-adamantan-1-yl) phenyl)sulfamoyl) phenyl) amino) benzoate (Intermediate-XVIII)

[0608] Intermediate-XVIII was prepared from Intermediate-XVII and methyl 2-bromobenzoate by a procedure similar to the one described in Intermediate-II.

[0609] .sup.1H NMR (400 MHz, DMSO-d6) δ 10.01 (s, 1H), 9.31 (s, 1H), 7.89 (d, J=8.4 Hz, 1H), 7.63 (d, J=8.4 Hz, 2H), 7.50 (t, J=7.6 Hz, 1H), 7.42 (d, J=8.0 Hz, 1H), 7.24-7.19 (m, 4H), 7.03-6.99 (m, 3H), 3.77 (s, 3H), 2.00 (s, 3H), 1.76 (s, 6H), 1.69 (s, 6H); LC-MS: m/z 517.1 (M+H).sup.+

[0610] The below intermediates were prepared by a procedure similar to Intermediate-XVIII using appropriate reactants and reagents employing suitable Pd catalysts and ligands and in presence of suitable solvents and appropriate reaction conditions.

TABLE-US-00024 Inter- mediate CP No. Reactant Structure Analytical data 306 XVIII.1 Int- XVII [00843] .sup.1H NMR (400 MHz, DMSO- d6) δ 10.33 (s, 1H), 10.05 (s, 1H), 8.48-8.47 (m, 1H), 8.31- 8.29 (m, 1H), 7.89 (d, J = 8.8 Hz, 2H), 7.69 (d, J = 8.8 Hz, 2H), 7.20 (d, J = 8.8 Hz, 2H), 7.03-6.99 (m, 3H), 3.90 (s, 3H), 1.99 (s, 3H), 1.76 (s, 6H), 1.68 (s, 6H). LC-MS: m/z 518.0 (M + H).sup.+ 312 XVIII.2 Int- XVII [00844] .sup.1H NMR (400 MHz, DMSO- d6) δ 9.96 (s, 1H), 9.81 (s, 1H), 7.99 (d, J = 8.8 Hz, 2H), 7.79 (t, J = 8.0 Hz, 1H), 7.63 (d, J = 8.8 Hz, 2H), 7.53 (d, J = 7.2 Hz, 1H), 7.19 (d, J = 8.8 Hz, 2H), 7.11 (d, J = 8.4 Hz, 1H), 7.02 (d, J = 8.4 Hz, 2H), 4.36-4.30 (m, 2H), 1.98 (s, 3H), 1.76 (s, 6H), 1.68 (s, 6H), 1.35 (t, J = 6.8 Hz, 3H). LC-MS: m/z 532.2 (M + H).sup.+ 342 XVIII.3 XVI.4 [00845] .sup.1H NMR (400 MHz, DMSO- d6) δ 10.33 (s, 1H), 8.49 (s, 1H), 7.89-8-7.86 (m, 1H), 7.58-7.56 (m, 3H), 7.51-7.49 (m, 1H), 7.43 (s, 1H), 7.34- 7.27 (m, 2H), 7.16-7.12 (m, 1H), 6.81 (d, J = 8.8 Hz, 2H), 3.84 (s, 3H), 2.05 (s, 3H), 1.85 (s, 6H), 1.73 (s, 6H). LC-MS: m/z 551.1 (M + H).sup.+ 372 XVIII.4 XVII.1 [00846] LC-MS: m/z 517.2 (M + H).sup.+ 392 XVIII.5 XVII.2 [00847] .sup.1H NMR (400 MHz, DMSO- d6) δ 9.72 (s, 1H), 9.37 (s, 1H), 7.92 (dd, J.sub.1 = 1.6 Hz, J.sub.2 = 8.0 Hz, 1H), 7.61 (d, J = 9.2 Hz, 2H), 7.55-7.51 (m, 1H), 7.45 (d, J = 7.6 Hz, 1H), 7.32 (d, J = 2.4 Hz, 1H), 7.27- 7.25 (m, 3H), 7.17 (d, J = 8.4 Hz, 1H), 7.04-7.00 (m, 1H), 3.81 (s, 3H), 2.02 (s, 3H), 1.80 (d, J = 2.8 Hz, 6H), 1.70 (s, 6H). 393 XVIII.6 XVII.2 [00848] .sup.1H NMR (400 MHz, DMSO- d6) δ 10.38 (s, 1H), 9.72 (s, 1H), 8.49 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 4.8 Hz, 1H), 8.31 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 7.6 Hz, 1H), 7.92 (d, J = 8.8 Hz, 2H), 7.67 (d, J = 8.8 Hz, 2H), 7.30 (d, J = 2.0 Hz, 1H), 7.25-7.24 (m, 1H), 7.17 (d, J = 8.4 Hz, 1H), 7.02 (dd, J.sub.1 = 4.8 Hz, J.sub.2 = 7.6 Hz, 1H), 3.91 (s, 3H), 2.01 (s, 3H), 1.79 (s, 6H), 1.69 (s, 6H). LC-MS: m/z 552.2 (M + H).sup.+ 396 XVIII.7 XVII.3 [00849] LC-MS: m/z 577.2 (M + H).sup.− 397 XVIII.8 XVII.3 [00850] .sup.1H NMR (400 MHz, DMSO- d6) δ 10.40 (s, 1H), 9.75 (s, 1H), 8.49 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 4.8 Hz, 1H), 8.32 (dd, J.sub.1 = 1.6 Hz, J.sub.2 = 7.6 Hz, 1H), 7.93 (d, J = 8.4 Hz, 2H), 7.65 (d, J = 8.8 Hz, 2H), 7.29-7.24 (m, 2H), 7.16 (d, J = 8.4 Hz, 1H), 7.02 (dd, J.sub.1 = 4.8 Hz, J.sub.2 = 7.6 Hz, 1H), 3.91 (s, 3H), 2.10-2.09 (m, 1H), 1.62 (s, 2H), 1.45-1.29 (m, 8H), 1.14 (s, 2H), 0.82 (s, 6H). LC-MS: m/z 580.2 (M + H).sup.+

Intermediate-XIX

[0611] ##STR00851##

Step-a: Synthesis of phenyl (4-((3r,5r,7r)-adamantan-1-yl)phenyl)carbamate (XIXa)

[0612] A solution of Intermediate-I.1 (0.5 g, 2.2 mmol, 1 eq.) and phenyl chloroformate (0.42 g, 2.64 mmol, 1.2 eq.) in DCM was added with triethylamine (0.44 g, 4.4 mmol, 2 eq.) and stirred at RT for 2 h. Reaction mixture was washed with water, concentrated in vacuo and purified by combi-flash to afford title compound as white solid (0.48 g, 630%).

[0613] .sup.1H NMR (400 MHz, DMSO-d6) δ10.10 (s, 1H), 7.44-7.39 (m, 4H), 7.31-7.19 (m, 5H), 2.05 (s, 3H), 1.84 (s, 6H), 1.73 (s, 6H); LC-MS: m/z 348.1 (M+H).sup.+

Step-b: Synthesis of methyl 2-(4-(3-(4-((3R,5R)-adamantan-1-yl) phenyl)ureido)phenyl) amino) nicotinate (Intermediate-XIX)

[0614] Intermediate-XIXa (0.285 g, 0.82 mmol, 1 eq.) and methyl 2-((4-aminophenyl)amino) nicotinate (0.2 g, 0.82 mmol, 1 eq.) were taken in THF (20 mL) and added with triethylamine (0.8 mL) and refluxed overnight. Reaction mass was concentrated in vacuo, the obtained crude was washed with n-hexane twice and dried under vacuum. The crude was taken further without purification.

[0615] .sup.1H NMR (400 MHz, DMSO-d6) δ 9.96 (s, 1H), 8.52 (d, J=14.0 Hz, 2H), 8.38-8.37 (m, 1H), 7.76 (d, J=8.4 Hz, 2H), 7.41-7.35 (m, 4H), 7.25 (d, J=8.4 Hz, 2H), 6.84 (dd, J.sub.1=4.4 Hz, J.sub.2=8.0 Hz, 1H), 3.87 (s, 3H), 2.05 (s, 3H), 1.84 (s, 6H), 1.73 (s, 6H); LC-MS: m/z 497.2 (M+H).sup.+

[0616] The below intermediates were prepared by a procedure similar to Intermediate-XIX using appropriate reactants and reagents and in presence of suitable solvents and appropriate reaction conditions.

TABLE-US-00025 Inter- mediate CP No. Reactant Structure Analytical data 300 XIX.1 VII.14 & Int-I.1 [00852] .sup.1H NMR (400 MHz, DMSO-d6) δ 9.18 (s, 1H), 8.45 (d, J = 13.2 Hz, 2H), 7.73-7.66 (m, 3H), 7.39-7.34 (m, 5H), 7.25 (d, J = 8.4 Hz, 2H), 6.99 (d, J = 8.4 Hz, 1H), 4.35-4.30 (m, 2H), 2.05 (s, 3H), 1.84 (s, 6H), 1.73 (s, 6H), 1.35 (t, J = 7.2 Hz, 3H). LC-MS: m/z 511.1 (M + H).sup.+ 307 XIX.2 XI.13 & Int-I.1 [00853] .sup.1H NMR (400 MHz, DMSO-d6) δ 9.21 (s, 1H), 8.61 (s, 1H), 8.52 (s, 1H), 7.88 (d, J = 7.8 Hz, 1H), 7.47 (d, J = 8.3 Hz, 2H), 7.38-7.36 (m, 3H), 7.26 (d, J = 8.8 Hz, 2H), 7.18 (d, J = 8.3 Hz, 2H), 7.05 (d, J = 8.3 Hz, 1H), 6.75- 6.73 (m, 1H), 3.85 (s, 3H), 2.05 (s, 3H), 1.84 (s, 6H), 1.73 (s, 6H). LC-MS: m/z 496.1 (M + H).sup.+ 299 XIX.3 XI.17 & Int-I.1 [00854] LC-MS: m/z 511.1 (M + H).sup.+

Intermediate-XIX.4

[0617] ##STR00855##

Step-a: Synthesis of methyl ((4-((4-((3R,5S)-adamantan-1-yl)-2-chlorophenyl) amino)phenyl) carbamoyl) prolinate (XIX.4)

[0618] A solution of Intermediate-XI (0.1 g, 0.283 mmol, 1 eq.) in DCM (10 mL) at 0° C. was added with triphosgene (0.084 g, 0.283 mmol, 1 eq.) drop wise and stirred at 0° C. for 1 h. This solution was added to a solution of methyl prolinate (0.056 g, 0.32 mmol, 1.2 eq.) in DCM (10 mL) and stirred at 0° C. for 1 h. Quenched with sat. bicarbonate solution and extracted with DCM, purified by column chromatography to afford title product as pale brown solid (0.13 g, 90%).

[0619] .sup.1H NMR (400 MHz, DMSO-d6) δ 8.18 (s, 1H), 7.34 (d, J=8.8 Hz, 2H), 7.28 (d, J=2.0 Hz, 1H), 7.26 (s, 1H), 7.14 (dd, J.sub.1=2.0 Hz, J.sub.2=8.0 Hz, 1H), 7.04 (d, J=8.8 Hz, 1H), 6.96 (d, J=9.6 Hz, 2H), 4.37-4.34 (m, 1H), 3.62 (s, 3H), 3.56-3.46 (m, 2H), 2.21-2.14 (m, 1H), 2.03 (s, 3H), 1.98-1.84 (m, 3H), 1.81 (d, J=2.4 Hz, 6H), 1.71 (s, 6H); LC-MS: m/z 508.4 (M+H).sup.+

[0620] The below intermediates were prepared by a procedure similar to Intermediate-XIX.4 using appropriate reactants and reagents and in presence of suitable solvents and appropriate reaction conditions.

TABLE-US-00026 Inter- mediate CP No. Reactant Structure Analytical data 114 XIX.5 Int-XI [00856] .sup.1H NMR (400 MHz, DMSO-d6) δ 8.18 (s, 1H), 7.34 (d, J = 8.8 Hz, 2H), 7.28 (d, J = 2.0 Hz, 1H), 7.26 (s, 1H), 7.14 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 8.0 Hz, 1H), 7.04 (d, J = 8.8 Hz, 1H), 6.96 (d, J = 9.6 Hz, 2H), 4.37- 4.34 (m, 1H), 3.62 (s, 3H), 3.56-3.46 (m, 2H), 2.21-2.14 (m, 1H), 2.03 (s, 3H), 1.98-1.84 (m, 3H), 1.81 (d, J = 2.4 Hz, 6H), 1.71 (s, 6H). LC-MS: m/z 508.2 (M + H).sup.+ 134 XIX.6 XI.2 [00857] .sup.1H NMR (400 MHz, DMSO-d6) δ 8.24 (s, 1H), 7.47 (s, 1H), 7.41 (d, J = 6.8 Hz, 2H), 7.33 (d, J = 1.6 Hz, 1H), 7.28-7.17 (m, 4H), 7.13-7.06 (m, 4H), 4.38-4.35 (m, 1H), 3.76 (s, 3H), 3.63-3.48 (m, 2H), 2.27 (s, 3H), 2.25-2.17 (m, 1H), 1.96-1.84 (m, 3H). LC-MS: m/z 464.1 (M + H).sup.+

Intermediate-XX

[0621] ##STR00858##

Step-a: Synthesis of methyl 2-((4-((4-((3R,5R)-adamantan-1-yl)phenyl)(methyl) amino) phenyl) (methyl) amino) benzoate (Intermediate-XX)

[0622] A solution of intermediate-VI (4 g, 8.85 mmol, 1 eq.) in DMF (80 mL) was cooled to 0° C. and added with sodium hydride (1.06 g, 44.2 mmol, 5 eq.) portion wise and stirred for 15 minutes. Methyl iodide (6.3 g, 44.2 mmol, 5 eq.) was added drop wise and the reaction mass was heated at 80° C. for 16 h in a seal tube. Reaction mass was cooled to RT and poured in to cold water. The precipitated solid was filtered and dried. This crude was absorbed over silica and purified by combi-flash to afford title product as pale-yellow solid (3 g, 70.70%).

[0623] .sup.1H NMR (400 MHz, DMSO-d6) δ 7.65 (dd, J.sub.1=2.0 Hz, J.sub.2=8.0 Hz, 1H), 7.60 (t, J=7.6 Hz, 1H), 7.33 (d, J=7.6 Hz, 1H), 7.26 (t, J=7.2 Hz, 1H), 7.13 (d, J=8.8 Hz, 2H), 6.90 (d, J=8.8 Hz, 2H), 6.67 (d, J=8.8 Hz, 2H), 6.59 (d, J=8.8 Hz, 2H), 3.55 (s, 3H), 3.20 (s, 3H), 3.13 (s, 3H), 2.02 (s, 3H), 1.80 (s, 6H), 1.71 (s, 6H); LC-MS: m/z 480.25 (M+H).sup.+

[0624] The below intermediates were prepared by a procedure similar to Intermediate-XX using appropriate reactants and reagents and in presence of suitable solvents and appropriate reaction conditions.

TABLE-US-00027 Intermediate CP No. Reactant Structure Analytical data 198 XX.1 Int-XII [00859] .sup.1H NMR (400 MHz, DMSO-d6) δ 8.31 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 4.8 Hz, 1H), 7.62 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 7.2 Hz, 1H), 7.49 (d, J = 2.4 Hz, 1H), 7.41 (dd, J.sub.1 = 2.4 Hz, J.sub.2 = 8.4 Hz, 1H), 7.26 (d, J = 8.4 Hz, 1H), 6.85-6.80 (m, 3H), 6.42 (d, J = 9.2 Hz, 2H), 3.31 (s, 3H), 3.25 (s, 3H), 3.15 (s, 3H), 2.07 (s, 3H), 1.89 (s, 6H), 1.74 (s, 6H). 233 XX.2 VI.36 [00860] LC-MS: m/z 480.25 (M + H).sup.+ 236 XX.3 XII.18 [00861] .sup.1H NMR (400 MHz, DMSO-d6) δ 8.31 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 4.9 Hz, 1H), 7.71 (s, 1H), 7.70 (d, J = 1.4 Hz, 1H), 7.39 (d, J = 1.9 Hz, 1H), 7.32 (d, J = 2.0 Hz, 2H), 7.04 (d, J = 8.3 Hz, 1H), 6.88-6.85 (m, 1H), 5.28 (s, 2H), 3.39 (s, 3H), 3.26 (s, 3H), 2.04 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 491.3 (M + H).sup.+ 246 XX.4 VI.40 [00862] .sup.1H NMR (400 MHz, DMSO-d6) δ 8.35 (d, J = 3.2 Hz, 1H), 7.69 (d, J = 5.6 Hz, 1H), 7.25 (d, J = 8.4 Hz, 2H), 6.92-6.86 (m, 7H), 3.37 (s, 3H), 3.31 (s, 3H), 3.19 (s, 3H), 2.04 (s, 3H), 1.84 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 482.1 (M + H).sup.+ 247 XX.5 VI.41 [00863] .sup.1H NMR (400 MHz, DMSO-d6) δ 8.37 (dd, J.sub.1 = 1.9 Hz, J.sub.2 = 4.8 Hz, 1H), 7.78 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 7.4 Hz, 1H), 7.25 (d, J = 8.3 Hz, 2H), 7.12 (t, J = 7.8 Hz, 1H), 7.00 (d, J = 8.8 Hz, 2H), 6.94-6.90 (m, 1H), 6.56 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 8.3 Hz, 1H), 6.51 (dd, J.sub.1 = 1.5 Hz, J.sub.2 = 7.9 Hz, 1H), 6.40 (t, J = 1.9 Hz, 1H), 3.38 (s, 3H), 3.30 (s, 3H), 3.17 (s, 3H), 2.04 (s, 3H), 1.82 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 482.1 (M + H).sup.+ 260 XX.6 Int-XV [00864] LC-MS: m/z 495.2 (M + H).sup.+ (Obtained acid directly) 266 XX.7 XII.68 [00865] LC-MS: m/z 536.1 (M + H).sup.+ (obtained acid directly) 270 XX.8 XII.67 [00866] LC-MS: m/z 468.1 (M + H).sup.+ 271 XX.9 XII.33 [00867] .sup.1H NMR (400 MHz, DMSO-d6) δ 8.52 (dd, J.sub.1 = 1.2 Hz, J.sub.2 = 4.8 Hz, 1H), 7.93 (dd, J.sub.1 = 1.6 Hz, J.sub.2 = 7.6 Hz, 1H), 7.30 (d, J = 9.2 Hz, 2H), 7.22 (d, J = 8.4 Hz, 1H), 7.14-7.11 (m, 3H), 6.44 (d, J = 8.8 Hz, 2H), 3.50 (s, 3H), 3.42 (s, 3H), 3.05 (s, 3H), 2.02 (s, 3H), 1.74 (s, 6H), 1.67 (s, 6H). LC-MS: m/z 550.1 (M + H).sup.+ 273 XX.10 XII.34 [00868] .sup.1H NMR (400 MHz, DMSO-d6) δ 7.82-7.78 (m, 1H), 7.42-7.38 (m, 1H), 7.46-7.44 (m, 2H), 7.11-7.05 (m, 3H), 6.81-6.78 (m, 2H), 6.38 (d, J = 8.8 Hz, 2H), 3.60 (s, 3H), 3.27 (s, 3H), 3.02 (s, 3H), 2.02 (s, 3H), 1.79 (s, 6H), 1.70 (s, 6H). LC-MS: m/z 549.1 (M + H).sup.+ 275 XX.11 XII.35 [00869] .sup.1H NMR (400 MHz, DMSO-d6) δ 7.69 (d, J = 2.8 Hz, 1H), 7.56- 7.52 (m, 2H), 7.32 (d, J = 8.4 Hz, 2H), 7.26 (d, J = 8.0 Hz, 1H), 7.15 (t, J = 6.8 Hz, 1H), 7.10 (d, J = 8.8 Hz, 2H), 6.93 (dd, J.sub.1 = 2.8 Hz, J.sub.2 = 9.2 Hz, 1H), 6.53 (d, J = 9.2 Hz, 1H), 3.53 (s, 3H), 3.29 (s, 3H), 3.18 (s, 3H), 2.05 (s, 3H), 1.86 (s, 6H), 1.73 (s, 6H). LC-MS: m/z 482.25 (M + H).sup.+ 276 XX.12 XV.19 [00870] .sup.1H NMR (400 MHz, DMSO-d6) δ 7.71 (d, J = 6.4 Hz, 1H), 7.63 (t, J = 7.3 Hz, 1H), 7.36 (m, 2H), 7.16 (m, 1H), 7.13 (d, J = 8.8 Hz, 2H), 6.99 (d, J = 8.8 Hz, 2H), 6.62 (m, 4H), 3.57 (s, 3H), 3.28 (m, 4H), 3.25 (s, 3H), 3.18 (s, 3H), 1.50 (m, 4H), 1.23 (m, 4H), 0.86 (m, 6H). 277 XX.13 VI.45 [00871] LC-MS: m/z 451.1 (M + H).sup.+ (obtained acid directly) 286 XX.14 XII.36 [00872] .sup.1H NMR (400 MHz, DMSO-d6) δ 7.69 (dd, J.sub.1 = 1.6 Hz, J.sub.2 = 8.0 Hz, 1H), 7.64-7.60 (m, 1H), 7.43 (d, J = 2.8 Hz, 1H), 7.36- 7.25 (m, 3H), 6.84-6.78 (m, 3H), 6.60 (d, J = 8.8 Hz, 2H), 3.54 (s, 3H), 3.21 (s, 3H), 2.04 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 502.1 (M + H).sup.+ 296 XX.15 VI.49 [00873] .sup.1H NMR (400 MHz, DMSO-d6) δ 7.68-7.55 (m, 2H), 7.38-7.05 (m, 4H), 6.95-6.83 (m, 2H), 6.75-6.55 (m, 4H), 3.54 (s, 3H), 3.20 (s, 3H), 3.13 (s, 3H), 2.10 (m, 1H), 1.62 (s, 2H), 1.46- 1.33 (m, 8H), 1.16 (s, 2H), 0.83 (s, 6H). LC-MS: m/z 509.2 (M + H).sup.+ 305 XX.16 VI.45 [00874] .sup.1H NMR (400 MHz, DMSO-d6) δ 7.67 (d, J = 7.8 Hz, 1H), 7.63- 7.59 (m, 1H), 7.35 (d, J = 8.4 Hz, 1H), 7.30-7.26 (m, 1H), 7.10 (t, J = 8.0 Hz, 2H), 6.94 (t, J = 8.4 Hz, 4H), 6.73 (d, J = 8.8 Hz, 2H), 6.65-6.60 (m, 5H), 3.56-3.53 (m, 5H), 3.21 (s, 3H), 3.17 (s, 3H), 1.53-1.48 (m, 2H), 1.33-1.28 (m, 2H), 0.87 (t, J = 6.9 Hz, 3H). LC-MS: m/z 494.1 (M + H).sup.+ 310 XX.17 Int-XV [00875] .sup.1H NMR (400 MHz, DMSO-d6) δ 9.24 (s, 1H), 7.88 (d, J = 8.0 Hz, 1H), 7.40-7.38 (m, 1H), 7.28-7.19 (m, 5H), 7.09 (d, J = 8.4 Hz, 2H), 7.02 (d, J = 8.4 Hz, 2H), 6.88 (t, J = 7.2 Hz, 1H), 3.90 (s, 3H), 3.34 (s, 3H), 2.02 (s, 3H), 1.81 (s, 6H), 1.70 (s, 6H). LC-MS: m/z 495.1 (M + H).sup.+ 314 XX.18 XII.40 [00876] .sup.1H NMR (400 MHz, DMSO-d6) δ 8.39 (dd, J.sub.1 = 1.4 Hz, J.sub.2 = 4.4 Hz, 1H), 7.44 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 7.9 Hz, 1H), 7.35 (d, J = 8.8 Hz, 2H), 7.03 (d, J = 9.3 Hz, 2H), 6.9-6.89 (m, 5H), 3.41 (s, 3H), 3.31 (s, 3H), 2.09 (s, 3H), 1.85 (s, 6H), 1.73 (s, 6H). LC-MS: m/z 469.3 (M + H).sup.+ 325 XX.19 XVIII.1 [00877] LC-MS: m/z 532.2 (M + H).sup.+ 326 XX.20 VI.53 [00878] LC-MS: m/z 511.4 (M + H).sup.+ 355 XX.21 XX.19 [00879] LC-MS: m/z 546.1 (M + H).sup.+ 357 XX.22 XIV.16 [00880] .sup.1H NMR (400 MHz, DMSO-d6) δ 7.69 (d, J = 8.0 Hz, 1H), 7.65- 7.60 (m, 1H), 7.39-7.30 (m, 3H), 7.15-7.07 (m, 3H), 6.94 (d, J = 8.8 Hz, 2H), 6.76 (d, J = 8.0 Hz, 1H), 6.60 (d, J = 8.8 Hz, 2H), 3.56 (s, 3H), 3.22 (s, 3H), 3.18 (s, 3H), 2.03 (s, 9H), 1.64 (s, 6H). LC-MS: m/z 524.3 (M + H).sup.+ 360 XX.23 XII.51 [00881] .sup.1H NMR (400 MHz, DMSO-d6) δ 7.71 (d, J = 7.8 Hz, 1H), 7.61 (d, J = 7.4 Hz, 1H), 7.43 (d, J = 7.8 Hz, 2H), 7.35-7.30 (m, 3H), 7.21-7.16 (m, 3H), 6.94 (d, J = 8.8 Hz, 2H), 6.86 (d, J = 8.4 Hz, 1H), 6.64 (d, J = 8.8 Hz, 2H), 3.56 (s, 3H), 3.22 (s, 3H), 2.94 (m, 1H), 1.13 (d, J = 6.4 Hz, 6H), LC-MS: m/z 486.2 (M + H).sup.+ 362 XX.24 XII.52 [00882] .sup.1H NMR (400 MHz, DMSO-d6) δ 7.45 (t, J = 8.0 Hz, 1H), 7.13 (t, J = 8.4 Hz, 2H), 6.97 (d, J = 8.4 Hz, 1H), 6.91 (d, J = 8.8 Hz, 2H), 6.81 (d, J = 8.0 Hz, 1H), 6.71-6.57 (m, 4H), 3.79 (s, 3H), 3.57 (s, 3H), 3.14 (s, 3H), 3.09 (s, 3H), 2.03 (s, 3H), 1.80 (s, 6H), 1.71 (s, 6H). LC-MS: m/z 511.2 (M + H).sup.+ 587 XX.25 XII.122 [00883] LC-MS: m/z 418.2 (M + H)+

[0625] The below compounds were prepared by a procedure similar to Intermediate-VI using appropriate reactants and reagents employing suitable Pd catalysts and ligands and in presence of suitable solvents and appropriate reaction conditions.

TABLE-US-00028 Com- pound No No Reactant Structure Analytical data 51 1 [00884] .sup.1H NMR (500 MHz, CDCl.sub.3) δ 9.45 (s, 1H), 8.01 (s, 1H), 7.5-7.7.30 (m, 2H), 7.2-7.1 (m, 2H), 6.98 (s, 1H), 6.8 (s, 1H), 6.78-6.26 (m, 4H), 5.99 (s, 1H), 3.90 (s, 3H), 2.23- 1.97 (m, 15H) LC-MS: m/z 453.3 (M + H).sup.+ 54 2 [00885] LC-MS: m/z 453.1 (M + H).sup.+ 57 3 [00886] .sup.1H NMR (500 MHz, CDCl.sub.3) δ 9.45 (s, 1H), 8.01 (s, 1H), 7.45-7.23. (d, 2H), 7.23-7.01 (m, 6H), 6.98-7.01 (d, 2H), 6.94 (s, 1H), 3.93 (s, 3H), 5.99 (s, 1H), 2.21-1.98 (m, 15H) LC-MS: m/z 521.6 (M + H).sup.+ 68 4 [00887] LC-MS: m/z 481.1 (M + H).sup.+ 70 5 [00888] LC-MS: m/z 561.2 (M + H).sup.2+ 79 6 [00889] LC-MS: m/z 515.3 (M + H).sup.+ 85 7 Int-XI [00890] .sup.1H NMR (400 MHz, DMSO- d6) δ 8.17 (s, 1H), 7.58 (dd, J.sub.1 = 1.6 Hz, J.sub.2 = 8.0 Hz, 1H), 7.44-7.40 (m, 2H), 7.32 (d, J = 2.0 Hz, 1H), 7.20-7.12 (m, 2H), 7.09-7.01 (m, 5H), 6.84 (t, J = 7.2 Hz, 1H), 2.04 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 454.1 (M + H).sup.+ 104 8 Int-XI [00891] .sup.1H NMR (400 MHz, DMSO- d6) δ 9.23 (s, 1H), 7.57 (s, 1H), 7.34 (s, 1H), 7.2 (d, J = 4.8 Hz, 4H), 7.12 (d, J = 8.8 Hz, 2H), 7.03-6.99 (m, 3H), 6.2 (d, J = 8.4 Hz, 1H), 6.05 (d, J = 8.4 Hz, 1H), 2.04 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 489.2 (M + H).sup.+ 201 9 III.5 & Int-1 [00892] .sup.1H NMR (400 MHz, DMSO- d6) δ 8.59 (s, 1H), 7.95 (s, 1H), 7.64 (s, 1H), 7.34 (s, 1H), 7.21 (s, 2H), 7.16 (d J = 8.4 Hz, 2H), 6.94 (d, J = 8.4 Hz, 2H), 5.28 (s, 2H), 2.04 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 350.2 (M + H).sup.+; Triazole fragment 225 10 Int-XI [00893] .sup.1H NMR (500 MHz, CDCl.sub.3) δ 8.18-8.17 (m, 1H), 7.49- 7.45 (m, 1H), 7.32 (d, J = 1.6 Hz, 1H), 7.28-7.25 (m, 2H), 7.16-7.09 (m, 4H), 6.76 (d, J = 8.0 Hz, 1H), 6.72-6.69 (m, 1H), 6.40 (s, 1H), 5.93 (s, 1H), 2.09 (s, 3H), 1.87 (s, 6H), 1.80-1.71 (m, 6H). LC- MS: m/z 430.3 (M + H).sup.+ 264 11 Compound 10 [00894] .sup.1H NMR (400 MHz, DMSO- d6) δ 8.71 (d, J = 6.0 Hz, 1H), 8.26 (t, J = 7.2 Hz, 1H), 8.05 (s, 1H), 7.63 (t, J = 6.4 Hz, 1H), 7.42 (d, J = 2.0 Hz, 1H), 7.37 (d, J = 8.4 Hz, 1H), 7.31- 7.29 (m, 1H), 7.19 (d, J = 8.8 Hz, 2H), 7.09 (d, J = 8.8 Hz, 2H), 6.92 (d, J = 8.8 Hz, 1H), 4.96 (t, J = 6.8 Hz, 2H), 3.22 (t, J = 7.2 Hz, 2H), 2.06 (s, 3H), 1.86 (s, 6H), 1.73 (s, 6H). LC-MS: m/z 484.1 (M).sup.+ ion 238 12 XII.28 [00895] .sup.1H NMR (400 MHz, DMSO- d6) δ 9.77 (s, 1H), 8.32-8.27 (m, 2H), 7.48-7.39 (m, 4H), 7.29 (d, J = 8.3 Hz, 1H), 6.83- 6.76 (m, 1H), 6.52 (d, J = 9.3 Hz, 2H), 4.99-4.95 (m, 1H), 4.31 (t, J = 4.9 Hz, 2H), 3.74- 3.71 (m, 2H), 3.18 (s, 3H), 2.07 (s, 3H), 1.89 (s, 6H), 1.74 (s, 6H). LC-MS: m/z 532.2 (M + H).sup.+ 347 13 II.27 & 1.1 [00896] .sup.1H NMR (400 MHz, DMSO- d6) δ 7.69 (s, 1H), 7.15 (d, J = 8.8 Hz, 2H), 7.10 (d, J = 7.2 Hz, 1H), 7.02-6.96 (m, 5H), 6.90 (d, J = 8.8 Hz, 4H), 6.73 (t, J = 7.6 Hz, 1H), 2.19 (s, 3H), 2.03 (s, 3H), 1.82 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 409.3 (M + H).sup.+ 352 14 XII.48 [00897] .sup.1H NMR (400 MHz, DMSO- d6) δ 7.95 (d, J = 16.0 Hz, 1H), 7.86 (s, 1H), 7.79 (s, 1H), 7.68 (dd, J.sub.1 = 1.2 Hz, J.sub.2 = 8.0 Hz, 1H), 7.267-7.22 (m, 1H), 7.17 (d, J = 8.4 Hz, 2H), 7.09 (d, J = 7.6 Hz, 1H), 6.98 (d, J = 9.2 Hz, 2H), 6.94- 6.85 (m, 5H), 6.49 (d, J = 16.0 Hz, 1H), 4.18 (q, J = 14.0 Hz, 2H), 2.04 (s, 3H), 1.82 (d, J = 2.34 Hz, 6H), 1.72 (s, 6H), 1.25 (t, J = 9.2 Hz, 3H). LC- MS: m/z 493.2 (M + H).sup.+ 375 15 XII.56 [00898] .sup.1H NMR (400 MHz, DMSO- d6) δ 8.24 (s, 1H), 7.31-7.24 (m, 3H), 7.12-6.94 (m, 8H), 6.33 (d, J = 8.0 Hz, 1H), 3.0 (t, J = 6.8 Hz, 2H), 2.68 (t, J = 5.6 Hz, 2H), 2.05 (s, 3H), 1.85 (d, J = 2.8 Hz, 6H), 1.70 (s, 6H). LC-MS: m/z 449.3 (M + H).sup.+ 354 16 XV.14 [00899] .sup.1H NMR (400 MHz, DMSO- d6) δ 9.95 (s, 1H), 9.70 (s, 1H), 8.01 (d, J = 8.8 Hz, 2H), 7.92 (d, J = 8.8 Hz, 2H), 7.81- 7.75 (m, 1H), 7.69 (d, J = 8.4 Hz, 2H), 7.51 (d, J = 7.6 Hz, 1H), 7.31 (d, J = 8.8 Hz, 2H), 7.13 (d, J = 8.0 Hz, 1H), 4.36- 4.35 (m, 2H), 2.06 (s, 3H), 1.86 (s, 6H), 1.74 (s, 6H), 1.38 (t, J = 7.2 Hz, 3H). LC- MS: m/z 496.2 (M + H).sup.+ 381 17 Int-XII [00900] .sup.1H NMR (400 MHz, DMSO- d6) δ 9.93 (s, 1H), 8.37 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 4.4 Hz, 1H), 8.22 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 7.6 Hz, 1H), 7.55 (d, J = 8.8 Hz, 2H), 7.41 (s, 1H), 7.31 (d, J = 1.6 Hz, 1H), 7.19-7.12 (m, 2H), 7.04 (d, J = 8.8 Hz, 2H), 6.84-6.81 (m, 1H), 3.89 (s, 3H), 2.04 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 488.1 (M + H).sup.+ 351 18 Int-XI [00901] .sup.1H NMR (400 MHz, DMSO- d6) δ 10.76 (s, 1H), 8.45 (d, J = 7.2 Hz, 1H), 8.04 (d, J = 6.8 Hz, 1H), 7.90-7.86 (m, 2H), 7.76 (s, 1H), 7.69 (d, J = 8.8 Hz, 2H), 7.37 (s, 1H), 7.28-7.25 (m, 2H), 7.08 (d, J = 8.4 Hz, 2H), 2.05 (s, 3H), 1.85 (s, 6H), 1.73 (s, 6H). LC-MS: m/z 518.05 (M + H).sup.+ 406 19 I.1 [00902] .sup.1H NMR (400 MHz, DMSO- d6) δ 10.71 (s, H), 8.01 (d, J = 7.6 Hz, 1H), 7.87 (t, J = 8.0 Hz, 1H), 7.77 (d, J = 8.8 Hz, 2H), 7.51-7.45 (m, 3H), 4.00 (s, 3H), 2.07 (s, 3H), 1.88 (s, 6H), 1.74 (s, 6H). LC-MS: m/z 423.2 (M + H).sup.+ 472 20 XI.16 [00903] 1H-NMR (400 MHz, CDCl3): δ 9.43 (s, 1H), 8.10 (s, 1H), 7.89 (d, J = 8.8 Hz, 1H), 7.33 (d, J = 2 Hz, 1H), 7.27 (d, J = 2 Hz, 2H), 7.16 (d, J = 8.4 Hz, 2H), 7.01-6.98 (m, 4H), 6.82 (dd, J1 = 1.6 Hz & J2 = 8.4 Hz, 1H), 3.87 (s, 3H), 3.69 (t, J = 5.2 Hz, 2H), 3.41 (s, 3H), 3.30 (s, 3H), 2.58 (t, J = 5.6 Hz, 2H), 2.08 (s, 3H), 1.90 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 568.3 (M + H)+. 529 21 XI.25 [00904] 1H NMR (400 MHz, DMSO-d6): δ 8.68 (s, 1H), 7.55 (d, J = 8.8 Hz, 2H), 7.48 (d, J = 2.4 Hz, 1H), 7.32 (dd, J1 = 1.6 & J2 = 8 Hz, 2H), 7.09 (d, J = 5.2 Hz, 1H), 7.05-6.99 (m, 3H), 6.93 (d, J = 8.8 Hz, 2H), 2.36 (d, J = 5.2 Hz, 3H), 2.14 (s, 1H), 1.69 (s, 2H), 1.52-1.35 (m, 8H), 1.18 (s, 2H), 0.86 (s, 6H). LC-MS: m/z 424.2 (M + H)+ 531 22 XI.25 [00905] 1H NMR (400 MHz, DMSO-d6): δ 7.75 (d, J = 4.4 Hz, 2H), 7.51-7.47 (m, 2H), 7.34 (dd, J1 = 2 Hz, & J2 = 8.4 Hz, 1H), 7.24 (d, J = 8.4 Hz, 2H), 7.14 (d, J = 8 Hz, 1H), 7.05-6.94 (m, 4H), 3.24 (s, 3H), 2.14 (s, 1H), 1.69 (s, 2H), 1.53-1.33 (m, 8H), 1.18 (s, 2H), 0.86 (s, 6H). LC-MS: m/z 536.2 (M + H)+ 534 23 IX.4 [00906] 1H NMR (400 MHz, DMSO-d6): δ 8.50 (s, 1H), 8.22 (s, 1H), 8.07 (d, J = 8.4 Hz, 1H), 8.02 (s, 1H), 7.77- 7.73 (m, 2H), 7.56 (d, J = 8 Hz, 1H), 7.49 (d, J = 1.2 Hz, 1H), 7.37 (dd, J1 = 2 Hz & J2 = 8.4 Hz, 1H), 7.21 (d, J = 8 Hz, 1H), 7.13 (t, J = 7.6 Hz, 1H), 2.41 (d, J = 4.8 Hz, 3H), 2.06 (s, 3H), 1.88 (s, 6H), 1.74 (s, 6H), LC-MS: m/z 525.2 (M + H)+. 608 24 XI.32 [00907] 1H NMR (400 MHz, DMSO-d6) δ 8.27 (s, 1H), 7.44 (d, J = 8.8 Hz, 2H), 7.33- 7.31 (m, 2H), 7.21 (dd, J1 = 3.2 Hz, J2 = 9.2 Hz, 1H), 7.10 (dd, J1 = 2.0 Hz, J2 = 6.4 Hz, 2H), 6.99 (dd, J1 = 2.4 Hz, J2 = 6.8 Hz, 2H), 6.76 (d, J = 8.8 Hz, 2H), 3.78 (s, 3H), 3.25 (s, 3H). LC-MS: m/z 398.1 (M + H)+. 629 25 XI.53 [00908] 1H NMR (400 MHz, DMSO-d6) δ 7.11-7.07 (m, 4H), 6.87 (s, 1H), 6.83 (d, J = 8.8 Hz, 2H), 6.77 (d, J = 2.4 Hz, 2H), 6.71 (d, J = 8.4 Hz, 1H), 6.53 (s, 1H), 3.75 (s, 3H), 3.18 (s, 3H), 2.05 (s, 3H), 2.49-2.48 (m, 1H), 1.77-1.76 (m, 5H), 1.37-1.32 (m, 5H). LC-MS: m/z 469.3 (M + H)+. 657 26 XI.53 [00909] 1H NMR (400 MHz, DMSO-d6) δ 8.55 (s, 1H), 7.84 (d, J = 2.0 Hz, 1H), 7.64 (dd, J1 = 2.0 Hz, J2 = 9.6 Hz, 1H), 7.25 (d, J = 4.8 Hz, 1H), 7.18 (d, J = 8.4 Hz, 2H), 7.03 (d, J = 8.0 Hz, 3H), 6.86 (d, J = 2.0 Hz, 1H), 6.74 (dd, J1 = 2.4 Hz, J2 = 8.4 Hz, 1H), 6.49 (d, J = 8.8 Hz, 1H), 3.24 (s, 3H), 2.46-2.43 (m, 1H), 2.38 (d, J = 4.8 Hz, 3H), 2.06 (s, 3H), 1.80-1.68 (m, 5H), 1.40-1.29 (m, 5H). LC-MS: m/z 489.2 (M + H)+. 688 27 VII [00910] 1H NMR (400 MHz, DMSO-d6) δ 9.35 (s, 1H), 7.70-7.66 (m, 1H), 7.50-7.48 (m, 2H), 7.38 (s, 1H), 7.31- 7.26 (m, 2H), 7.18-7.15 (m, 1H), 7.21-7.10 (m, 1H), 7.06-7.02 (m, 3H), 2.04 (s, 3H), 1.82 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 455.20 (M + H)+ 694 28 VII [00911] 1H NMR (400 MHz, DMSO-d6) δ 9.32 (s, 1H), 7.72 (t, J = 7.6 Hz, 1H), 7.62 (d, J = 8.4 Hz, 2H), 7.43-7.42 (m, 1H), 7.32-7.30 (m, 2H), 7.17 (d, J = 7.2 Hz, 2H), 7.09 (d, J = 8.4 Hz, 1H), 7.03 (d, J = 8.8 Hz, 2H), 6.94 (d, J = 8.0 Hz, 1H), 2.60 (d, J = 4.4 Hz, 3H), 2.04 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H). LC-MS: m/z m/z 523.2 (M + H)+

[0626] The below compounds were prepared by a procedure similar to Intermediate-XIII using appropriate reactants and reagents and in presence of suitable solvents and appropriate reaction conditions.

TABLE-US-00029 Compound CP No Reactant Structure Analytical data 86 29 Int-XI [00912] .sup.1H NMR (400 MHz, DMSO-d6) δ 7.20 (d, J = 2.0 Hz, 1H), 7.03 (dd, J.sub.1 = 1.6 Hz, J.sub.2 = 8.0 Hz, 1H), 6.87 (d, J = 8.8 Hz, 2H), 6.82 (s, 1H), 6.71 (d, J = 8.8 Hz, 1H), 6.60 (d, J = 8.8 Hz, 2H), 5.28 (d, J = 8.4 Hz, 1H), 4.03-4.00 (m, 1H), 3.89-3.81 (m, 2H), 3.11-3.06 (m, 1H), 2.02-1.90 (m, 5H), 1.88-1.78 (m, 8H), 1.73-1.61 (m, 7H), 1.56-1.49 (m, 1H), 0.96 (t, J = 7.2 Hz, 3H). LC-MS: m/z (M + H)+ 87 30 Int-XI [00913] .sup.1H NMR (400 MHz, DMSO-d6) δ (d, J = 2.0 Hz, 1H), 7.03 (dd, J.sub.1 = 1.6 Hz, J.sub.2 = 8.0 Hz, 1H), 6.89 (d, J = 8.8 Hz, 2H), 6.83 (s, 1H), 6.71 (d, J = 8.8 Hz, 1H), 6.53 (d, J = 8.8 Hz, 2H), 5.55-5.50 (m, 1H), 4.05-4.03 (m, 2H), 3.97-3.91 (m, 1H), 2.69-2.61 (m, 1H), 2.02-1.95 (m, 5H), 1.79 (s, 6H), 1.78-1.68 (m, 9H), 1.54-1.45 (m, 1H), 1.15 (t, J = 7.2 Hz, 3H). LC-MS: m/z 493.2 (M + H).sup.+ 516 31 Compound 257 [00914] 1H-NMR (400 MHz, DMSO-d6): 7.14- 7.02 (m, 5H), 6.91 (d, J = 8.8 Hz, 2H), 6.79-6.76 (m, 1H), 6.71-6.50 (m, 4H), 5.21-5.17 (m, 1H), 4.46 (d, J = 7 Hz, 2H), 3.74 (s, 3H), 3.13 (s, 3H), 2.03 (s, 3H), 1.81-1.79 (m, 6H), 1.72-1.70 (m, 6H). LC-MS: m/z 469.3 (M + H)+.

[0627] The below compound was prepared by a procedure similar to Intermediate-XI using appropriate reactants and reagents and in presence of suitable solvents and appropriate reaction conditions.

TABLE-US-00030 Compound CP No Reactant Structure Analytical data 231 32 XII.69 [00915] .sup.1H NMR (400 MHz, DMSO-d6) δ 7.60 (s, 1H), 7.55 (d, J = 8.8 Hz, 2H), 7.46 (dd, J.sub.1 = 1.2 Hz, J.sub.2 = 4.8 Hz, 1H), 7.27 (d, J = 2.0 Hz, 1H), 7.15-7.11 (m, 2H), 7.02-7.00 (m, 3H), 6.87-6.85 (m, 1H), 6.58- 6.56 (m, 1H), 5.00 (s, 2H), 2.03 (s, 3H), 1.81 (s, 6H), 1.71 (s, 6H). LC-MS: m/z 445.2 (M + H).sup.+

[0628] The below compound was prepared by a procedure similar to Intermediate-XIX using appropriate reactants and reagents and in presence of suitable solvents and appropriate reaction conditions.

TABLE-US-00031 Compound CP No Reactant Structure Analytical data 82 33 I.1 [00916] .sup.1H NMR (400 MHz, DMSO-d6) δ 8.20 (s, 1H), 7.38 (d, J = 8.8 Hz, 2H), 7.20 (d, J = 8.8 Hz, 2H), 4.37-4.34 (m, 1H), 3.60 (s, 3H), 3.56-3.45 (m, 2H), 2.20-2.16 (m, 1H), 2.03 (s, 3H), 1.96-1.92 (m, 3H), 1.83 (d, J = 2.0 Hz, 6H), 1.72 (s, 6H). LC-MS: m/z 383.1 (M + H).sup.+

Synthesis of 2-((4-((4-((3R,5R)-adamantan-1-yl)phenyl)amino) phenyl)amino)benzoic acid (Compound-24 (CP-55))

[0629] ##STR00917##

[0630] To a solution of Intermediate-VI (8.5 g, 16.5 mmol, 1 eq.) in THF:MeOH:H.sub.2O (40+40+20 mL) LiOH×H.sub.2O (3.3 g, 82.4 mmol, 5 eq.) was added and stirred at RT for 16 h. Reaction mass was concentrated in vacuo, diluted with water and acidified with 2 N HCl to pH 5. The precipitate obtained was filtered and dried under vacuum. This solid was washed with 10% ether in hexane mixture and dried to afford title product as off-white solid (5.5 g, 670).

[0631] .sup.1H NM/R (400 MHz, DMSO-d6) δ 12.99 (s, 1H), 9.42 (s, 1H), 8.00 (s, 1H), 7.85 (d, J=6.8 Hz, 1H), 7.32 (t, 1H), 7.21 (d, J=8.8 Hz, 2H), 7.11-6.96 (m, 7H), 6.67 (t, J=3.4 Hz, 1H), 2.08 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H); LC-MS: m/z 438.4 (M+H).sup.+

[0632] The below compounds were prepared by a procedure similar to the one described in compound-24 by using appropriate reagents in the presence of suitable solvents at appropriate reaction conditions. The physiochemical characteristics of the compounds are also summarized.

TABLE-US-00032 Com- pound Reac- CP No tant Structure Analytical data 52 25 [00918] LC-MS: m/z 439.1 (M + H).sup.+ 58 26 [00919] LC-MS: m/z 507.2 (M + H).sup.+ 59 27 [00920] LC-MS: m/z 506.2 (M − H).sup.− 60 28 [00921] LC-MS: m/z 521.2 (M + H).sup.+ 61 29 [00922] LC-MS: m/z 575.2 (M + H).sup.+ 62 30 [00923] LC-MS: m/z 457.2 (M + H).sup.+ 64 31 VI.1 [00924] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.99 (bs, 1H), 9.48 (s, 1H), 7.86 (d, J = 7.3 Hz, 1H), 7.52 (s, 1H), 7.33 (t, J = 7.4 Hz, 2H), 7.20 (s, 2H), 7.13 (d, J = 8.8 Hz, 2H), 7.05 (d, J = 8.8 Hz, 2H), 7.01 (s, 1H), 6.68 (t, J = 7.4 Hz, 1H), 2.04 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 472.1 (M + H).sup.+ 65 32 [00925] LC-MS: m/z 454.1 (M + H).sup.+ 66 33 [00926] LC-MS: m/z 539.1 (M − H).sup.− 67 34 [00927] MLC-MS: m/z 440.2 (M + H).sup.+ 69 35 Int-XV [00928] .sup.1H NMR (400 MHz, DMSO-d6) δ 13.2 (s, 1H), 10.02 (s, 1H), 9.81 (s, 1H), 7.97-7.94 (m, 3H), 7.69 (d, J = 8.8 Hz, 2H), 7.51-7.43 (m, 2H), 7.35-7.31 (m, 4H), 6.93- 6.89 (m, 1H), 2.06 (s, 3H), 1.87 (s, 6H), 1.74 (s, 6H). LC-MS: m/z 467.1 (M + H).sup.+ 71 36 [00929] LC-MS: m/z 545.1 (M).sup.+ 80 37 [00930] LC-MS: m/z 501.1 (M − H).sup.+ 83 38 Com- pound 23 [00931] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.36 (s, 1H), 8.16 (s, 1H), 7.38 (d, J = 8.8 Hz, 2H), 7.19 (d, J = 8.8 Hz, 2H), 4.31- 4.28 (m, 1H), 3.54-3.50 (m, 1H), 3.46-3.40 (m, 1H), 2.16-2.14 (m, 1H), 2.03 (s, 3H), 1.95-1.85 (m, 3H), 1.82 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 369.1 (M + H).sup.+ 88 39 Com- pound 20 [00932] .sup.1H NMR (400 MHz, DMSO-d6) δ 7.21 (d, J = 2.4 Hz, 1H), 7.03 (d, J = 1.6 Hz, 1H), 6.87 (d, J = 8.4 Hz, 2H), 6.83 (s, 1H), 6.75 (d, J = 8.8 Hz, 1H), 6.61 (d, J = 8.8 Hz, 2H), 3.96-3.90 (m, 1H), 2.99- 2.93 (m, 1H), 2.02-1.79 (m, 6H), 1.78-1.69 (m, 7H), 1.70-1.62 (m, 7H), 1.59-1.51 (m, 1H). LC-MS: m/z 465.2 (M + H).sup.+ 89 40 Com- pound 21 [00933] .sup.1H NMR (400 MHz, DMSO-d6) δ 7.21 (d, J = 2.4 Hz, 1H), 7.06 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 8.8 Hz, 1H), 6.89 (d, J = 8.8 Hz, 2H), 6.76 (d, J = 8.0 Hz, 1H), 6.56 (d, J = 8.8 Hz, 2H), 3.93-3.91 (m, 1H), 2.61-2.59 (m, 1H), 2.02- 1.97 (m, 5H), 1.78 (s, 6H), 1.75-1.66 (m, 9H), 1.52-1.44 (m, 1H). LC-MS: m/z 465.1 (M + H).sup.+ 93 41 VI.2 [00934] .sup.1H NMR (400 MHz, DMSO-d6) δ 13.00 (bs, 1H), 9.52 (s, 1H), 7.88 (dd, J.sub.1 = 1.5 Hz, J.sub.2 = 8.3 Hz, 1H), 7.69 (s, 1H), 7.42-7.30 (m, 4H), 7.25 (dd, J.sub.1 = 8.3 Hz, J.sub.2 = 12.7 Hz, 1H), 7.21-7.07 (m, 8H), 6.71 (t, J = 7.3 Hz, 1H), 3.06-3.02 (m, 1H), 1.14 (d, J = 6.8 Hz, 6H). LC-MS: m/z 457.1 (M + H).sup.+ 98 42 Isomer- 1 of com- pound 41 [00935] .sup.1H NMR (400 MHz, DMSO-d6) δ 7.21 (d, J = 4.0 Hz, 1H), 7.04 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 8.4 Hz, 1H), 6.87 (d, J = 8.8 Hz, 2H), 6.82 (s, 1H), 6.74 (d, J = 8.8 Hz, 1H), 6.60 (d, J = 8.8 Hz, 2H), 3.93- 3.89 (m, 1H), 2.95-2.92 (m, 1H), 2.02 (s, 3H), 1.99-1.93 (m, 1H), 1.88- 1.78 (m, 8H), 1.74-1.63 (m, 7H), 1.57-1.50 (m, 1H), 1.35-1.33 (m, 1H). LC-MS: m/z 465.2 (M + H).sup.+ 99 43 Isomer- 2 of com- pound 41 [00936] .sup.1H NMR (400 MHz, DMSO-d6) δ 7.20 (d, J = 2.0 Hz, 1H), 7.04 (d, J = 8.8 Hz, 1H), 6.87 (d, J = 8.8 Hz, 2H), 6.82 (s, 1H), 6.75 (d, J = 8.8 Hz, 1H), 6.60 (d, J = 8.8 Hz, 2H), 3.93-3.89 (m, 1H), 2.95-2.92 (m, 1H), 2.02 (s, 3H), 1.99-1.92 (m, 1H), 1.88-1.78 (m, 8H), 1.74-1.63 (m, 7H), 1.57- 1.50 (m, 1H), 1.35-1.33 (m, 1H). LC-MS: m/z 465.2 (M + H).sup.+ 100 44 Isomer- 1 of com- pound 42 [00937] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.15 (bs, 1H), 7.21 (d, J = 2.4 Hz, 1H), 7.04 (dd, J.sub.1 = 2.4 Hz, J.sub.2 = 8.8 Hz, 1H), 6.89 (d, J = 8.8 Hz, 2H), 6.83 (s, 1H), 6.74 (d, J = 8.8 Hz, 1H), 6.55 (d, J = 8.8 Hz, 2H), 5.50 (bs, 1H), 3.92 (m, 1H), 2.67-2.57 (m, 1H), 2.02 (s, 3H), 1.99- 1.93 (m, 2H), 1.79 (s, 6H), 1.75-1.68 (m, 9H), 1.50-1.44 (m, 1H). LC- MS: m/z 46.52 (M + H).sup.+ 101 45 Isomer- 2 of com- pound 42 [00938] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.18 (bs, 1H), 7.21 (d, J = 2.0 Hz, 1H), 7.04 (dd, J.sub.1 = 1.6 Hz, J.sub.2 = 8.8 Hz, 1H), 6.89 (d, J = 8.8 Hz, 2H), 6.83 (s, 1H), 6.74 (d, J = 8.8 Hz, 1H), 6.55 (d, J = 8.8 Hz, 2H), 5.50 (bs, 1H), 3.93- 3.91 (m, 1H), 2.67-2.57 (m, 1H), 2.02-1.94 (m, 5H), 1.78 (s, 6H), 1.77- 1.68 (m, 8H), 1.49-1.46 (m, 1H). LC-MS: m/z 465.2 (M + H).sup.+ 102 46 XIII.1 [00939] .sup.1H NMR (400 MHz, DMSO-d6) δ 7.21 (d, J = 2.0 Hz, 1H), 7.04 (dd, J.sub.1 = 2.4 Hz, J.sub.2 = 8.8 Hz, 1H), 6.89 (s, 1H), 6.87 (s, 2H), 6.77 (d, J = 8.0 Hz, 1H), 6.66 (d, J = 8.8 Hz, 2H), 3.87 (s, 1H), 2.62 (m, 1H), 2.02 (s, 3H), 1.91-1.78 (m, 8H), 1.70 (s, 6H), 1.68- 1.42 (m, 4H), 1.41-1.25 (m, 2H). LC-MS: m/z 479.2 (M + H).sup.+ 103 47 XIII.1 [00940] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.00 (bs, 1H), 7.20 (d, J = 2.0 Hz, 1H), 7.03 (d, J = 6.8 Hz, 1H), 6.87 (d, J = 8.8 Hz, 2H), 6.82 (s, 1H), 6.75 (d, J = 8.8 Hz, 1H), 6.57 (d, J = 8.0 Hz, 2H), 5.20 (bs, 1H), 3.40-3.36 (m, 1H), 2.22-2.01 (m, 1H), 2.02 (s, 3H), 1.82-1.78 (m, 2H), 1.78 (s, 6H), 1.70-1.65 (m, 9H), 1.51- 1.42 (m, 1H), 1.38-1.29 (m, 1H), 1.09-1.02 (m, 1H), LC-MS: m/z 479.2 (M + H).sup.+ 106 48 XV.2 [00941] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.4 (bs, 1H), 8.01 (bs, 1H), 7.44- 7.40 (m, 3H), 7.33-7.27 (m, 2H), 6.91 (d, J = 8.3 Hz, 2H), 4.37 (m, 1H), 3.58 (bs, 2H), 2.25-2.22 (m, 1H), 2.05 (s, 3H), 1.85 (s, 9H), 1.73 (s, 6H). LC-MS: m/z 479.2 (M + H).sup.+ 107 49 XV.3 [00942] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.4 (bs, 1H), 7.99 (bs, 1H), 7.42- 7.38 (m, 3H), 7.31-7.25 (m, 2H), 6.89 (d, J = 8.3 Hz, 2H), 4.35 (m, 1H), 3.56 (m, 2H), 2.23-2.20 (m, 1H), 2.03 (s, 3H), 1.83 (s, 9H), 1.71 (s, 6H). LC-MS: m/z 479.2 (M + H).sup.+ 108 50 XIX.4 [00943] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.36 (s, 1H), 8.13 (s, 1H), 7.35 (d, J = 8.8 Hz, 2H), 7.28 (d, J = 2.4 Hz, 1H), 7.25 (s, 1H), 7.14 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 8.0 Hz, 1H), 7.04 (d, J = 8.8 Hz, 1H), 6.96 (d, J = 8.8 Hz, 2H), 4.31- 4.29 (m, 1H), 3.56-3.42 (m, 2H), 2.18-2.12 (m, 1H), 2.03 (s, 3H), 1.95- 1.84 (m, 3H), 1.81 (s, 6H), 1.71 (s, 6H). LC- MS: m/z 494.2 (M + H).sup.+ 113 51 VI.3 [00944] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.96 (s, 1H), 9.52 (s, 1H), 7.88 (dd, J.sub.1 = 1.5 Hz, J.sub.2 = 7.8 Hz, 1H), 7.7 (s, 1H), 7.38-7.34 (m, 2H), 7.30- 7.16 (m, 10H), 7.08 (d, J = 8.3 Hz, 1H), 6.71 (t, J = 7.3 Hz, 1H), 2.27 (s, 3H). LC-MS: m/z 429.1 (M + H).sup.+ 114 52 XIX.5 [00945] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.36 (s, 1H), 8.13 (s, 1H), 7.35 (d, J = 8.8 Hz, 2H), 7.28 (d, J = 2.4 Hz, 1H), 7.25 (s, 1H), 7.14 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 8.0 Hz, 1H), 7.04 (d, J = 8.8 Hz, 1H), 6.96 (d, J = 8.8 Hz, 2H), 4.31- 4.29 (m, 1H), 3.56-3.42 (m, 2H), 2.18-2.12 (m, 1H), 2.03 (s, 3H), 1.95- 1.84 (m, 3H), 1.81 (s, 6H), 1.71 (s, 6H). LC- MS: m/z 492.4 (M + H).sup.− 115 53 VI.4 [00946] .sup.1H NMR (400 MHz, DMSO-d6) δ 13.00 (s, 1H), 9.52 (s, 1H), 7.88 (d, J = 7.9 Hz, 1H), 7.82 (d, J = 7.8 Hz, 1H), 7.75- 7.69 (m, 2H), 7.60 (t, J = 7.8 Hz, 1H), 7.44 (d, J = 7.2 Hz, 1H), 7.38-7.25 (m, 2H), 7.23-7.18 (m, 5H), 7.14-7.09 (m, 2H), 6.72 (t, J = 8.0 Hz, 1H). LC-MS: m/z 483.1 (M + H).sup.+ 116 54 VI.5 [00947] .sup.1H NMR (400 MHz, DMSO-d6) δ 13.00 (bs, 1H), 9.49 (s, 1H), 8.32 (s, 1H), 8.87 (dd, J.sub.1 = 7.8 Hz, J.sub.2 = 7.8 Hz, 1H), 7.88 (d, J = 1.4 Hz, 1H), 7.51 (dd, J.sub.1 = 2.4 Hz, J.sub.2 = 8.8 Hz, 1H), 7.43 (dd, J.sub.1 = 6.4 Hz, J2 = 8.8 Hz, 4H), 7.19- 7.14 (m, 4H), 7.10 (d, J = 8.3 Hz, 2H), 7.04 (d, J = 8.3 Hz, 1H), 6.70 (t, J = 7.9 Hz, 1H). LC-MS: m/z 433.1 (M + H).sup.+ 117 55 VI.5 [00948] .sup.1H NMR (400 MHz, DMSO- d6) δ 12.93 (s, 1H), 9.47 (s, 1H), 8.28 (s, 1H), 7.87 (d, J = 9.3 Hz, 1H), 7.64 (dd, J.sub.1 = 5.4 Hz, J.sub.2 = 8.3 Hz, 2H), 7.52 (d, J = 8.3 Hz, 2H), 7.33 (t, J = 7.4 Hz, 1H), 7.24 (t, J = 8.8 Hz, 2H), 7.14 (m, 6H), 7.03 (d, J = 8.3 Hz, 1H), 6.70 (t, J = 7.3 Hz, 1H). LC-MS: m/z (M + H).sup.+ 118 56 VI.6 [00949] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.96 (s, 1H), 9.51 (s, 1H), 7.88 (d, J1 = 1.5 Hz, J2 = 8.3 Hz, 1H), 7.69 (s, 1H), 7.53 (d, J = 2.0 Hz, 1H), 7.38-7.29 (m, 4H), 7.24- 7.15 (m, 5H), 7.09 (t, J = 8.4 Hz, 2H), 7.01 (t, J = 7.4 Hz, 1H), 6.71 (t, J = 7.8 Hz, 1H), 3.79 (s, 3H). LC-MS: m/z 445.1 (M + H).sup.+ 121 57 VI.7 [00950] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.95 (s, 1H), 9.53 (s, 1H), 7.89 (d, J = 1.0 Hz, 1H), 7.66 (s, 1H), 7.37-7.23 (m, 2H), 7.21-7.14 (m, 5H), 7.13-7.06 (m, 4H), 6.97 (dd, J.sub.1 = 1.4 Hz, J.sub.2 = 8.3 Hz, 1H), 6.71 (t, J = 7.3 Hz, 1H), 2.03 (s, 6H). LC-MS: m/z 442.4 (M + H).sup.+ 122 58 VI.8 [00951] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.98 (s, 1H), 9.54 (s, 1H), 7.88 (dd, J.sub.1 = 0.9 Hz, J.sub.2 = 7.8 Hz, 1H), 7.77 (s, 1H), 7.55 (dd, J.sub.1 = 6.8 Hz, J.sub.2 = 8.3 Hz, 1H), 7.48 (d, J = 1.5 Hz, 1H), 7.44-7.35 (m, 4H), 7.28-7.25 (m, 2H), 7.23-7.19 (m, 4H), 7.10 (d, J = 8.3 Hz, 1H), 6.72 (t, J = 7.3 Hz, 1H). LC-MS: m/z 449 (M + H).sup.+ 124 59 Int-XII [00952] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.18 (bs, 1H), 8.16-8.13 (m, 2H), 7.62 (d, J = 8.8 Hz, 2H), 7.27 (d, J = 2.0 Hz, 1H), .sup.1H NMR (400 MHz, DMSO-d6) δ 7.22 (s, 1H), 7.13 (dd, J.sub.1 = 2.4 Hz, J.sub.2 = 8.4 Hz, 1H), 7.04- 7.02 (m, 3H), 6.66 (dd, J.sub.1 = 4.8 Hz, J.sub.2 = 7.2 Hz, 1H), 2.03 (s, 3H), 1.82 (s, 6H), 1.71 (s, 6H). LC-MS: m/z 474 (M + H).sup.+ 125 60 VI.9 [00953] .sup.1H NMR (400 MHz, DMSO-d6) δ 13.61 (s, 1H), 10.6 (s, 1H), 8.5 (d, J = 8.8 Hz, 1H), 8.4 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 4.8 Hz, 1H), 8.28 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 8.0 Hz, 1H), 7.4 (d, J = 2.0 Hz, 1H), 7.32 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 8.8 Hz, 1H), 6.92 (dd, J.sub.1 = 4.4 Hz J.sub.2 = 7.2 Hz, 1H), 2.06 (s, 3H), 1.86 (d, J = 2.8 Hz, 6H), 1.7 (s, 6H). LC-MS: m/z 383.0 (M + H).sup.+ 126 611 VI.10 [00954] .sup.1H NMR (400 MHz, DMSO-d6) δ 13.00 (bs, 1H), 9.52 (bs, 1H), 7.87 (dd, J.sub.1 = 1.5 Hz, J.sub.2 = 7.8 Hz, 1H), 7.59 (s, 1H), 7.35- 7.05 (m, 12H), 6.71 (t, J = 6.9 Hz, 1H), 2.05 (s, 3H), 1.90 (s, 3H). LC-MS: m/z 443.1(M + H).sup.+ 127 62 VI.65 [00955] .sup.1H NMR (400 MHz, DMSO-d6) δ 13.45 (s, 1H), 10.79 (s, 1H), 8.55 (s, 1H), 8.49 (d, J = 8.4 Hz, 1H), 8.04 (d, J = 6.0 Hz, 1H), 7.94 (d, J = 7.2 Hz, 1H), 7.66 (d, J = 8.4 Hz, 1H), 7.41 (d, J = 2.0 Hz, 1H), 7.37-7.32 (m, 2H), 7.02 (t, J = 7.2 Hz, 1H), 6.29 (d, J = 5.2 Hz, 1H), 2.08 (s, 3H), 1.89 (s, 6H), 1.75 (s, 6H). LC-MS: m/z 475.1 (M + H).sup.+ 128 63 XIII.2 [00956] .sup.1H NMR (400 MHz, DMSO-d6) δ 11.9 (bs, 1H), 7.64 (s, 1H), 7.36 (s, 1H), 7.26-7.23 (m, 2H), 6.47 (bs, 1H), 6.40 (d, J = 9.3 Hz, 2H), 6.10 (bs, 1H), 3.91 (m, 1H), 2.94 (m, 1H), 2.05 (bs, 3H), 1.94 (m, 2H), 1.84 (s, 6H), 1.80-1.63 (m, 8H), 1.55-1.50 (m, 2H). LC-MS: m/z 533.2 (M + H).sup.+ 129 64 XIII.2 [00957] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.18 (s, 1H), 7.69 (s, 1H), 7.37 (s, 1H), 7.26 (s, 2H), 7.41- 7.38 (m, 2H), 6.30 (s, 1H), 6.08 (d, J = 6.8 Hz, 1H), 3.92-3.89 (m, 1H), 2.05 (s, 3H), 2.02-1.91 (m, 2H), 1.85 (s, 6H), 1.73 (s, 6H), 1.70-1.60 (m, 2H), 1.52-1.38 (m, 3H). LC-MS: m/z 533.2 (M + H).sup.+ 130 65 XIII.3 [00958] .sup.1H NMR (400 MHz, DMSO-d6) δ 7.0 (d, J = 8.0 Hz, 2H), 6.53 (d, J = 8.4 Hz, 2H), 3.93-3.88 (m, 1H), 2.94-2.64 (m, 1H), 1.99 (bs, 5H), 1.95- 1.77 (m, 2H), 1.75 (bs, 7H), 1.72-1.54 (bs, 7H). LC-MS: m/z 340.1 (M + H).sup.+ 131 66 XIII.4 [00959] .sup.1H NMR (400 MHz, DMSO-d6) δ 7.02 (d, J = 8.8 Hz, 2H), 6.55 (d, J = 8.4 Hz, 2H), 3.74 (bs, 1H), 2.08 (bs, 3H), 2.01- 1.88 (m, 1H), 1.77-1.73 (bs, 6H), 1.70 (bs, 8H), 1.53-1.47 (m, 4H), 1.37- 1.27 (m, 2H). LC-MS: m/z 354.1 (M + H).sup.+ 134 67 XIX.6 [00960] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.37 (bs, 1H), 8.21 (bs, 1H), 7.46- 7.41 (m, 3H), 7.39 (s, 1H), 7.33-7.17 (m, 4H), 7.13-7.06 (m, 4H), 4.3 (d, J = 6.4 Hz, 1H), 3.55-3.47 (m, 2H), 2.25 (s, 3H), 2.19-2.13 (m, 1H), 1.96- 1.88 (m, 3H). LC-MS: m/z 450.1 (M + H).sup.+ 135 68 VI.11 [00961] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.30- 10.99 (bs, 1H), 8.20 (s, 1H), 8.00-7.91 (m, 4H), 7.63 (d, J = 8.8 Hz, 2H), 7.55-7.48 (m, 4H), 7.33- 7.23 (m, 3H), 6.75 (t, J = 7.6 Hz, 1H). LC-MS: m/z 373.3 (M + H).sup.+ 136 69 XIII.5 [00962] .sup.1H NMR (400 MHz, DMSO-d6) δ 7.21 (d, J = 2.0 Hz, 1H), 7.05 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 10.8 Hz, 1H), 6.88 (d, J = 8.4 Hz, 2H), 6.83 (s, 1H), 6.76 (d, J = 8.8 Hz, 1H), 6.58 (d, J = 8.4 Hz, 2H), 3.8 (s, 1H), 2.03 (s, 3H), 1.90- 1.83 (m, 1H), 1.80-1.65 (m, 17H), 1.64-1.56 (m, 3H), 1.52-1.41 (m, 3H). LC-MS: m/z 507.3 (M + H).sup.+ 138 70 Int-XIII [00963] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.53 (bs, 1H), 8.81 (s, 1H), 7.79 (d, J = 8.0 Hz, 1H), 7.36- 7.32 (m, 1H), 7.18 (d, J = 2.0 Hz, 1H), 7.12 (d, J = 8.8 Hz, 1H), 6.79-6.74 (m, 2H), 6.52 (d, J = 7.2 Hz, 1H), 4.51 (d, J = 7.2 Hz, 1H), 3.7 (s, 1H), 3.48 (s, 1H), 2.02 (s, 3H), 1.78- 1.7 (m, 18H), 1.58-1.55 (m, 2H). LC-MS: m/z 479.3 (M + H).sup.+ 139 71 Int-XIII [00964] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.53 (s, 1H), 7.78-7.76 (m, 2H), 7.34 (t, J = 8.0 Hz, 1H), 7.17 (d, J = 2.0 Hz, 1H), 7.11 (dd, J.sub.1 = 1.2 Hz, J.sub.2 = 8.0 Hz, 1H), 6.78-6.73 (m, 2H), 6.54-6.50 (m, 1H), 4.5 (d, J = 8.4 Hz, 1H), 3.4- 3.35 (m, 2H), 2.08-1.98 (m, 7H), 1.78 (s, 6H), 1.7 (s, 6H), 1.47-1.23 (m, 4H). LC- MS: m/z 479.4 (M + H).sup.+ 140 72 VI.12 [00965] .sup.1H NMR (400 MHz, DMSO-d6) δ 13.00 (bs, 1H), 9.49 (bs, 1H), 7.86 (dd, J.sub.1 = 1.5 Hz, J.sub.2 = 7.9 Hz, 1H), 7.42 (s, 1H), 7.37 (s, 1H), 7.34 (m, 1H), 7.28-7.25 (m, 1H), 7.18-7.04 (m, 6H), 6.70 (t, J = 7.4 Hz, 1H), 5.91 (s, 1H), 2.38-2.32 (m, 2H), 1.91-1.89 (m, 2H), 1.77- 1.74 (m, 2H), 1.05 (m, 6H). LC-MS: m/z 446.3 (M + H).sup.+ 141 73 VI.13 [00966] .sup.1H NMR (400 MHz, DMSO-d6) δ 13.00-12.8 (bs, 1H), 8.34 (s, 2H), 7.90-7.82 (m, 2H), 7.32 (d, J = 10.0 Hz, 2H), 7.26- 7.13 (m, 3H), 6.96 (bs, 1H), 1.98 (s, 3H), 1.83 (d, J = 2.4 Hz, 6H), 1.72 (s, 6H), 1.33 (s, 9H). LC- MS: m/z 575.1 (M + H).sup.+ 142 74 VI.14 [00967] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.91 (bs, 1H), 8.77 (s, 1H), 8.30 (s, 1H), 8.05 (s, 1H), 7.89- 7.86 (m, 1H), 7.77 (d, J = 8.4 Hz, 1H), 7.55-7.51 (m, 1H), 7.38-7.37 (m, 2H), 7.27 (t, J = 2.0 Hz, 2H), 2.05 (s, 3H), 1.85 (s, 6H), 1.73 (s, 6H), 1.33 (s, 9H). LC-MS: m/z 575.1 (M + H).sup.+ 143 75 Int-XI [00968] .sup.1H NMR (400 MHz, DMSO-d6) δ 13.40- 13.00 (bs, 1H), 8.66 (s, 1H), 8.09 (d, J = 2.0 Hz, 1H), 7.76 (s, 1H), 7.37 (d, J = 1.2 Hz, 1H), 7.28- 7.22 (m, 2H), 7.17 (d, J = 7.6 Hz, 2H), 7.06 (d, J = 8.0 Hz, 2H), 6.89 (d, J = 6.8 Hz, 1H), 2.05 (s, 3H), 1.89-1.84 9bs, 6H), 1.73 (s, 6H). LC-MS: m/z 474.1 (M + H).sup.+ 144 76 VI.15 [00969] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.86 (bs, 1H), 7.97 (d, J = 2.8 Hz, 1H), 7.86 (dd, J.sub.1 = 1.6 Hz, J.sub.2 = 8.0 Hz, 1H), 7.77 (s, 1H), 7.54-7.48 (m, 2H), 7.41-7.33 (m, 3H), 7.21 (d, J = 8.4 Hz, 2H), 7.14 (d, J = 8.4 Hz, 1H), 2.04 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H), 1.32 (s, 9H). LC- MS: m/z 574.1 (M + H).sup.+ 145 77 XV.5 [00970] .sup.1H NMR (400 MHz, DMSO-d6) δ 11.93 (bs, 1H), 7.99 (s, 1H), 7.83 (bs, 1H), 7.66 (d, J = 8.8 Hz, 2H), 7.40 (s, 1H), 7.29-7.26 (m, 2H), 6.90 (d, J = 8.8 Hz, 2H), 4.54- 4.50 (m, 1H), 2.92-2.90 (m, 1H), 2.08 (bs, 3H), 2.05 (m, 2H), 1.85 (s, 6H), 1.83-1.80 (m, 2H), 1.73 (s, 6H), 1.52-1.49 (m, 2H). LC-MS: m/z (M + H).sup.+ 146 78 XII.9 [00971] .sup.1H NMR (400 MHz, DMSO-d6) δ 13.2 (s, 1H), 9.7 (s, 1H), 7.9 (dd, J.sub.1 = 1.6 Hz, J.sub.2 = 8.0 Hz, 1H), 7.52-7.39 (m, 5H), 7.34-7.24 (m, 5H), 7.16- 7.13 (m, 3H), 6.82 (t, J = 8.0 Hz, 1H). LC-MS: m/z 356.0 (M + H).sup.+ 148 79 [00972] LC-MS: m/z 467.3 (M + H).sup.+ 149 80 [00973] LC-MS: m/z 507.2 (M + H).sup.+ 151 81 [00974] LC-MS: m/z 438.2 (M).sup.+ 156 82 XII.10 [00975] .sup.1H NMR (400 MHz, DMSO-d6) δ 11.2 (s, 1H), 7.74 (s, 1H), 7.50 (d, J = 8.4 Hz, 1H), 7.4 (s, 1H), 7.31 (d, J = 2.0 Hz, 1H), 7.19-7.03 (m, 7H), 2.05 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 474.1 (M + H).sup.+ 157 83 XII.11 [00976] .sup.1H NMR (400 MHz, DMSO-d6) δ 13.80-13.2 (bs, 1H), 9.50-9.0 (bs, 1H), 8.39 (s, 1H), 7.92 (d, J = 5.2 Hz, 1H), 7.64 (d, J = 4.8 Hz, 1H), 7.55 (s, 1H), 7.34 (s, 1H), 7.21 (s, 2H), 7.14 (d, J = 9.2 Hz, 2H), 7.05 (d, J = 8.8 Hz, 2H), 2.05 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 474.1 (M + H).sup.+ 158 84 VI.16 [00977] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.80 (bs, 1H), 8.13 (s, 1H), 7.53 (s, 1H), 7.28 (s, 4H), 7.15- 7.14 (m, 2H), 7.08-7.04 (m, 5H), 2.04 (s, 3H), 1.82 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 472.1 (M + H).sup.+ 159 85 XII.12 [00978] .sup.1H NMR (400 MHz, DMSO-d6) δ 13.82 (bs, 1H), 10.41 (bs, 1H), 8.83 (bs, 1H), 8.68 (s, 1H), 7.55 (s, 1H), 7.52 (d, J = 8.8 Hz, 2H), 7.33 (d, J = 0.8 Hz, 1H), 7.22-7.17 (m, 2H), 7.04 (d, J = 8.8 Hz, 2H), 2.04 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 475.2 (M + H).sup.+ 160 86 XII.13 [00979] .sup.1H NMR (400 MHz, DMSO-d6) δ 10.17 (s, 1H), 8.37 (d, J = 2.4 Hz, 1H), 8.04 (d, J = 2.0 Hz, 1H), 7.51 (d, J = 8.4 Hz, 2H), 7.47 (s, 1H), 7.32 (d, J = 1.6 Hz, 1H), 7.18- 7.14 (m, 2H), 7.04 (d, J = 8.8 Hz, 2H), 2.04 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 475.2 (M + H).sup.+ 161 87 XV.6 [00980] .sup.1H NMR (400 MHz, DMSO-d6) δ 10.11 (s, 1H), 7.66 (d, J = 8.4 Hz, 2H), 7.41-7.39 (m, 1H), 7.35-7.31 (m, 1H), 7.23- 7.18 (m, 3H), 7.11-7.09 (m, 1H), 3.93 (t, J = 8.8 Hz, 2H), 3.79 (t, J = 7.2 Hz, 2H), 3.62-3.54 (m, 2H), 3.52-3.49 (m, 2H), 3.02-2.95 (m, 1H), 1.10 (d, J = 6.8 Hz, 6H). LC- MS: m/z 353.1 (M + H).sup.+ 162 88 XIII.6 [00981] .sup.1H NMR (400 MHz, DMSO-d6) δ 7.21-7.20 (m, 1H), 7.05-7.02 (m, 1H), 6.89-6.85 (m, 3H), 6.82-6.74 (m, 2H), 6.65- 6.58 (m, 5H), 3.79 (bs, 1H), 3.14-3.11 (m, 1H), 2.92-2.81 (m, 3H), 2.60- 2.56 (m, 1H), 2.34-2.32 (m, 1H), 2.02 (s, 3H), 1.78 (s, 7H), 1.70 (s, 8H). LC-MS: m/z 480.2 (M + H).sup.+ 163 89 XII.14 [00982] .sup.1H NMR (400 MHz, DMSO-d6) δ 13.80 (bs, 1H), 9.12 (s, 1H), 8.23 (d, J = 4.8 Hz, 1H), 7.55 (d, J = 8.4 Hz, 2H), 7.28- 7.27 (m, 3H), 7.13 (d, J = 1.2 Hz, 1H), 7.06-7.03 (m, 4H), 2.04 (s, 3H), 1.82 (s, 6H), 1.71 (s, 6H). LC-MS: m/z 474.3 (M + H).sup.+ 168 90 XII.15 [00983] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.80 (bs, 1H), 9.12 (s, 1H), 7.70- 7.64 (m, 3H), 7.36 (d, J = 7.2 Hz, 1H), 7.29 (d, J = 1.6 Hz, 1H), 7.25 (s, 1H), 7.15 (dd, J.sub.1 = 1.2 Hz, J.sub.2 = 8.0 Hz, 1H), 7.07- 7.02 (m, 3H), 6.96 (d, J = 8.4 Hz, 1H), 2.04 (s, 3H), 1.82 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 474.3 (M + H).sup.+ 169 91 XII.16 [00984] .sup.1H NMR (400 MHz, DMSO-d6) δ 13.95 (bs, 1H), 13.2 (bs, 1H), 8.35 (d, J = 2.4 Hz, 1H), 8.30 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 5.2 Hz, 1H), 8.20 (dd, J.sub.1 = 1.6 Hz, J.sub.2 = 8.0 Hz, 1H), 8.12 (s, 1H), 7.92 (d, J = 8.8 Hz, 1H), 7.87 (dd, J.sub.1 = 2.8 Hz, J.sub.2 = 8.8 Hz, 1H), 7.34 (d, J = 2.4 Hz, 1H), 7.26 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 8.8 Hz, 1H), 6.98 (d, J = 8.8 Hz, 1H), 6.80 (dd, J.sub.1 = 4.8 Hz, J.sub.2 = 8.0 Hz, 1H), 2.06 (s, 3H), 1.86 (s, 6H), 1.74 (s, 6H). LC-MS: m/z 475.2 (M + H).sup.+ 170 92 VI.17 [00985] .sup.1H NMR (400 MHz, DMSO-d6) δ 13.59 (bs, 1H), 10.58 (bs, 1H), 8.38-8.37 (m, 1H), 8.36 (s, 1H), 8.27 (dd, J.sub.1 = 1.6 Hz, J.sub.2 = 7.6 Hz, 1H), 7.55 (d, J = 2.4 Hz, 1H), 7.35 (dd, J.sub.1 = 2.4 Hz, J.sub.2 = 8.8 Hz, 1H), 6.91 (dd, J.sub.1 = 4.8 Hz, J.sub.2 = 7.6 Hz, 1H), 2.06 (s, 3H), 1.86 (s, 6H), 1.73 (s, 6H). LC-MS: m/z 428.9 (M + H).sup.+ 172 93 XIII.7 [00986] .sup.1H NMR (400 MHz, DMSO-d6) δ 7.21 (d, J = 1.2 Hz, 1H), 7.04 (d, J = 6.8 Hz, 1H), 6.93-6.88 (m, 3H), 6.77 (d, J = 8.4 Hz, 1H), 6.61 (d, J = 8.4 Hz, 2H), 5.70 (bs, 1H), 4.09 (bs, 1H), 3.30-3.27 (m, 3H), 3.21-3.17 (m, 1H), 2.87-2.84 (m, 1H), 2.67 (m, 1H), 2.02 (s, 3H), 1.78 (s, 6H), 1.70 (s, 6H). LC-MS: m/z 466.3 (M + H).sup.+ 173 94 VI.18 [00987] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.6 (bs, 1H), 7.42 (s, 1H), 7.32 (s, 1H), 7.16 (s, 2H), 7.09 (d, J = 7.6 Hz, 2H), 7.08- 7.00 (m, 1H), 6.93 (d, J = 8.4 Hz, 2H), 4.1 (m, 1H), 2.90 (m, 1H), 2.80 (m, 1H), 2.05 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H), 1.33 (s, 9H). LC-MS: m/z 523.2 (M − H).sup.+ 174 95 VI.18 & Com- pound 82 [00988] .sup.1H NMR (400 MHz, DMSO-d6) δ 7.49 (s, 1H), 7.33 (s, 1H), 7.19 (s, 1H), 7.11 (d, J = 8.4 Hz, 2H), 6.95 (d, J = 8.0 Hz, 2H), 3.65 (m, 1H), 3.12- 3.10 (m, 1H), 2.90-2.80 (m, 1H), 2.04 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 425.3 (M + H).sup.+ 177 96 VI.20 [00989] .sup.1H NMR (400 MHz, DMSO-d6) δ 13.50 (bs, 1H), 10.41 (bs, 1H), 8.37 (dd, J.sub.1 = 1.9 Hz, J.sub.2 = 4.9 Hz, 1H), 8.24 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 7.8 Hz, 1H), 7.66 (d, J = 7.8 Hz, 1H), 7.50 (s, 1H), 7.25 (t, J = 7.8 Hz, 1H), 7.03 (d, J = 7.8 Hz, 1H), 6.85-6.82 (m, 1H), 2.06 (s, 3H), 1.88 (s, 6H), 1.74 (s, 6H). LC-MS: m/z 349.2 (M + H).sup.+ 178 97 IV.1 [00990] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.5 (bs, 1H), 8.24 (s, 1H), 8.07 (d, J = 6.8 Hz, 1H), 8.01 (s, 0.3 H), 7.84 (m, 0.6H), 7.78-7.73 (m, 2H), 7.51-7.46 (m, 2H), 7.25- 7.19 (m, 1.5H), 2.09 (s, 3H), 1.98 (s, 6H), 1.77 (s, 6H), 1.49 (s, 2H). LC- MS: m/z 373.1 (M + H).sup.+ 182 294 98 XV.20 [00991] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.95 (s, 1H), 9.5 (s, 1H), 8.45 (s, 1H), 7.88 (dd, J.sub.1 = 1.6 Hz, J.sub.2 = 8.0 Hz, 1H), 7.67 (d, J = 8.8 Hz, 2H), 7.35 (t, J = 1.6 Hz, 1H), 7.23 (s, 1H), 7.20-7.14 (m, 4H), 7.07 (d, J = 8.4 Hz, 1H), 6.99 (d, J = 8.8 Hz, 2H), 6.73-6.69 (m, 1H), 2.06 (s, 9H), 1.65 (s, 6H). LC- MS: m/z 482.1 (M + H).sup.+ 183 99 [00992] LC-MS: m/z 453.3 (M + H).sup.+ 184 100 Int-XX [00993] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.80 (bs, 1H), 7.75 (dd, J.sub.1 = 0.8 Hz, J.sub.2 = 7.2 Hz, 1H), 7.58 (t, J = 8.0 Hz, 1H), 7.31 (t, J = 7.6 Hz, 2H), 7.12 (d, J = 8.8 Hz, 2H), 6.90 (d, J = 9.2 Hz, 2H), 6.67 (d, J = 8.8 Hz, 2H), 6.56 (d, J = 8.8 Hz, 2H), 3.18 (s, 3H), 3.13 (s, 3H), 2.02 (s, 3H), 1.80 (s, 6H), 1.71 (s, 6H). LC-MS: m/z 467.3 (M + H).sup.+ 185 101 VI.21 [00994] .sup.1H NMR (400 MHz, DMSO-d6) δ 7.81 (s, 1H), 7.38 (d, J = 8.8 Hz, 1H), 7.32-7.28 (m, 3H), 7.15-7.12 (m, 2H), 6.97 (d, J = 8.8 Hz, 1H), 4.72 (s, 2H), 2.02 (s, 3H), 1.81 (s, 6H), 1.71 (s, 6H). LC- MS: m/z 436.0 (M + H).sup.+ 186 102 XV.7 [00995] .sup.1H NMR (400 MHz, DMSO-d6) δ 11.59-11.3 (bs, 1H), 7.46 (d, J = 8.8 Hz, 2H), 7.39 (s, 1H), 7.30 (d, J = 2.4 Hz, 1H), 7.16 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 8.4 Hz, 1H), 7.10 (d, J = 8.0 Hz, 1H), 7.00 (d, J = 8.8 Hz, 2H), 4.47 (d, J = 8.0 Hz, 1H), 4.33 (d, J = 7.2 Hz, 1H), 2.04 (s, 3H), 1.82 (s, 6H), 1.72 (s, 6H), 1.38 (s, 3H), 1.35 (s, 3H), 1.25-1.22 (m, 1H). LC-MS: m/z 525.1 (M + H)+ 187 103 VI.22 [00996] .sup.1H NMR (400 MHz, DMSO-d6) δ 7.66 (s, 1H), 7.36 (s, 1H), 7.26- 7.23 (m, 4H), 6.96 (d, J = 8.4 Hz, 2H), 4.03 (d, J = 13.2 Hz, 1H), 3.83 (d, J = 12.8 Hz, 1H), 3.21- 3.18 (m, 2H), 2.78-2.71 (m, 1H), 2.33-2.32 (m, 1H), 2.15-2.02 (m, 4H), 1.95-1.79 (m, 4H), 1.74- 1.63 (m, 8H). LC-MS: m/z 465.3 (M + H).sup.+ 191 104 XII.17 [00997] .sup.1H NMR (400 MHz, DMSO-d6) δ 13.40 (bs, 1H), 10.20 (s, 1H), 8.34 (dd, J.sub.1 = 1.9 Hz, J.sub.2 = 4.9 Hz, 1H), 8.22 (dd, J.sub.1 = 1.9 Hz, J.sub.2 = 7.8 Hz, 1H), 7.95 9bs, 1H0, 7.55 (d, J = 8.8 Hz, 2H), 7.13 (t, J = 7.8 Hz, 1H), 7.05-7.00 (m, 3H), 6.85 (d, J = 7.8 Hz, 1H), 6.83-6.77 (m, 2H), 2.05 (s, 3H), 1.76 (s, 6H), 1.69 (s, 6H). LC-MS: m/z 440.1 (M + H).sup.+ 192 105 VI.23 [00998] .sup.1H NMR (400 MHz, DMSO-d6) δ 7.72 (s, 1H), 7.61 (s, 1H), 7.34 (s, 1H), 7.20 (s, 2H), 7.16- 7.13 (m, 3H), 6.95 (d, J = 8.4 Hz, 2H), 6.89 (s, 1H), 5.07 (s, 2H), 2.05 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 350.2 (M + H).sup.+ 194 106 X.4 [00999] .sup.1H NMR (400 MHz, DMSO-d6) δ 13.0 (s, 1H), 8.26-8.25 (m, 1H), 7.92 (d, J = 7.2 Hz, 1H), 7.44 (d, J = 7.6 Hz, 1H), 7.34-7.31 (m, 2H), 6.84 (dd, J.sub.1 = 4.4 Hz, J.sub.2 = 7.2 Hz, 1H), 3.57 (s, 2H), 3.33 (m, 8H), 2.05 (s, 2H), 1.85 (s, 6H), 1.73 (s, 6H). LC-MS: m/z 466.1 (M + H).sup.+ 195 107 X.5 [01000] .sup.1H NMR (400 MHz, DMSO-d6) δ 8.56 (dd, J.sub.1 = 1.6 Hz, J.sub.2 = 4.8 Hz, 1H), 8.18 (d, J = 7.6 Hz, 1H), 7.46 (dd, J.sub.1 = 4.8 Hz, J.sub.2 = 7.6 Hz, 1H), 7.42- 7.40 (m, 1H), 7.38-7.30 (m, 2H), 4.18 (s, 2H), 3.56 (s, 2H), 2.8 (s, 4H), 2.55-2.54 (m, 4H), 2.04 (s, 3H), 1.84 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 480.1 (M + H).sup.+ 197 108 VI.24 [01001] .sup.1H NMR (400 MHz, DMSO-d6) δ 13.2 (bs, 1.5H), 8.10 (s, 0.4H), 8.03 (s, 1H), 7.52 (d, J = 7.6 Hz, 1H), 7.45-7.40 (m, 2H), 7.31 (m, 2H), 7.17 (s, 1H), 7.14 (s, 2.5 H), 7.04-6.98 (m, 2H), 5.05 (s, 1H), 4.99 (s, 2H), 2.04 (s, 5H), 1.90 (s, 9H), 1.72 (s, 9H). LC-MS: m/z 436.2 (M + H).sup.+ 198 109 XX.1 [01002] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.35 (s, 1H), 8.28 (d, J = 3.2 Hz, 1H), 7.70 (d, J = 5.6 Hz, 1H), 7.47 (d, J = 1.6 Hz, 1H), 7.38 (d, J = 8.4 Hz, 1H), 7.24 (d, J = 8.4 Hz, 1H), 6.84-6.81 (m, 3H), 6.43 (d, J = 8.8 Hz, 2H), 3.3 (s, 3H), 3.13 (s, 3H), 2.06 (s, 3H), 1.88 (s, 6H), 1.74 (s, 6H). LC-MS: m/z 502.2 (M + H).sup.+ 199 110 VI.25 [01003] .sup.1H NMR (400 MHz, DMSO-d6) δ 13.2 (bs, 1H), 8.15 (s, 1H), 7.52 (d, J = 9.2 Hz, 1H), 7.37- 7.31 (m, 2H), 7.19-7.08 (m, 4H), 5.21 (s, 2H), 2.05 (s, 3H), 1.83 (s, 6H), 1.72 (s, 1H). LC-MS: m/z 436.3 (M + H).sup.+ 200 111 VI.26 [01004] .sup.1H NMR (400 MHz, DMSO-d6) δ 13.50 (bs, 1H), 10.40 (s, 1H), 8.36 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 4.9 Hz, 1H), 8.23 (dd, J.sub.1 = 1.9 Hz, J.sub.2 = 7.3 Hz, 1H), 8.11 (s, 1H), 7.66 (s, 1H), 7.19-7.11 (m, 3H), 7.02 (d, J = 8.3 Hz, 1H), 6.95 (d, J = 7.8 Hz, 1H), 6.86- 6.83 (m, 2H), 6.70 (d, J = 7.8 Hz, 1H), 1.98 (s, 3H), 1.85 (s, 6H), 1.68 (s, 6H). LC-MS: m/z 440.3 (M + H).sup.+ 202 112 XII.18 [01005] .sup.1H NMR (400 MHz, DMSO-d6) δ 13.4 (bs, 1H), 10.2 (bs, 1H), 8.33 (d, J = 2.8 Hz, 1H), 8.22 (s, 1H), 8.16 (dd, J.sub.1 = 1.2 Hz, J.sub.2 = 7.2 Hz, 1H), 7.67 (s, 1H), 7.39 (d, J = 2.0 Hz, 1H), 7.31=7.29 (m, 1H), 6.94 (d, J = 8.4 Hz, 1H), 6.74 (dd, J.sub.1 = 5.2 Hz, J.sub.2 = 7.6 Hz, 1H), 5.36 (bs, 2H), 2.04 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 463.2 (M + H).sup.+ 203 113 XII.19 [01006] .sup.1H NMR (400 MHz, DMSO-d6) δ 13.54 (s, 1H), 10.40 (s, 1H), 8.32 (dd, J.sub.1 = 1.9 Hz, J.sub.2 = 4.8 Hz, 1H), 8.23 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 7.8 Hz, 1H), 7.61 (d, J = 8.3 Hz, 1H), 7.39 (s, 1H), 7.30 (d, J = 8.3 Hz, 1H), 7.23-7.10 (m, 4H), 6.84 (m, 1H), 6.75 (d, J = 8.0 Hz, 1H), 4.02 (s, 2H), 3.16 (m, 1H), 1.10 (d, J = 6.8 Hz, 6H). LC-MS: m/z 347.2 (M + H).sup.+ 204 114 XII.20 [01007] .sup.1H NMR (400 MHz, DMSO-d6) δ 8.13 (d, J = 7.6 Hz, 2H), 7.48 (s, 1H), 7.42 (s, 1H), 7.33 (d, J = 2.0 Hz, 1H), 7.29 (d, J = 8.4 Hz, 1H), 7.26- 7.21 (m, 3H), 7.09 (t, J = 7.6 Hz, 1H), 6.67 (s, 1H), 6.55 (d, J = 7.6 Hz, 1H), 2.05 (s, 3H), 1.85 (s, 6H), 1.73 (s, 6H). LC-MS: m/z 474.2 (M + H).sup.+ 205 115 XII.21 [01008] .sup.1H NMR (400 MHz, DMSO-d6) δ 13.3 (bs, 1H), 9.63 (s, 1H), 8.41 (s, 1H), 8.33 (s, 1H), 7.70 (d, J = 8.8 Hz, 2H), 7.36 (s, 1H), 7.30 (d, J = 2.4 Hz, 1H), 7.18-7.16 (m, 1H), 7.11 (d, J = 8.4 Hz, 1H), 7.05 (d, J = 9.2 Hz, 2H), 2.05 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 475.2 (M + H).sup.+ 206 116 XII.22 [01009] .sup.1H NMR (400 MHz, DMSO-d6) δ 13.20 (bs, 1H), 8.40 (t, J = 1.9 Hz, 2H), 8.33 (s, 1H), 7.71 (m, 1H), 7.39 (s, 1H), 7.31 (s, 1H), 7.17-7.06 (m, 6H), 2.04 (s, 3H), 1.82 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 474.2 (M + H).sup.+ 207 117 XII.23 [01010] .sup.1H NMR (400 MHz, DMSO-d6) δ 9.96 (s, 1H), 7.99 (d, J = 6.8 Hz, 1H), 7.77 (s, 1H), 7.37 (s, 1H), 7.32 (s, 1H), 7.29- 7.23 (m, 2H), 7.15 (d, J = 8.8 Hz, 2H), 7.06 (d, J = 8.8 Hz, 2H), 6.9 (dd, J.sub.1 = 2.5 Hz, J.sub.2 = 6.9 Hz, 1H), 2.05 (bs, 3H), 1.84 (s, 6H), 1.73 (s, 6H). LC-MS: m/z 474.2 (M + H).sup.+ 210 118 VI.27 [01011] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.88 (bs, 1H), 7.88 (s, 1H), 7.75 (s, 1H), 7.57 (d, J = 8.8 Hz, 1H), 7.37 (d, J = 1.6 Hz, 1H), 7.31 (d, J = 8.0 Hz, 1H), 7.21 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 8.8 Hz, 1H), 7.02 (s, 1H), 6.91 (dd, J.sub.1 = 1.6 Hz, J.sub.2 = 8.8 Hz, 1H), 5.05 (s, 2H), 2.05 (s, 3H), 1.85 (s, 6H), 1.73 (s, 6H). LC-MS m/z 436.2 (M + H).sup.+ 211 119 XII.24 [01012] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.8 (bs, 1H), 9.5 (bs, 1H), 8.2 (bs, 1H), 7.9 9bs, 1H), 7.7 (bs, 1H), 7.46 (bs, 1H), 7.40 (bs, 2H), 7.30 (bs, 1H), 7.20 (bs, 1H), 7.00 (bs, 1H), 6.82 (bs, 1H), 2.05 (s, 3H), 1.90 (s, 6H), 1.73 (s, 6H). LC-MS: m/z 542.2 (M + H).sup.+ 212 120 XV.8 [01013] .sup.1H NMR (400 MHz, DMSO-d6) δ 13.2 (bs, 1H), 10.16 (bs, 1H), 8.15 (s, 1H), 7.53 (s, 1H), 7.42 (d, J = 6.0 Hz, 2H), 7.32 (s, 2H), 6.92 (s, 1H), 4.71 (d, J = 6.0 Hz, 1H), 4.67 (d, J = 6.0 Hz, 1H), 2.06 (s, 3H), 1.86 (s, 6H), 1.73 (s, 6H), 1.4 (s, 6H). LC-MS: m/z 593.2 (M + H).sup.+ 213 121 VI.28 [01014] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.25 (bs, 1H), 8.29 (s, 1H), 7.79 (s, 1H), 7.63 (s, 1H), 7.40 (s, 1H), 7.22 (s, 2H), 7.19- 7.15 (m, 2H), 6.97-6.92 (m, 2H), 5.23 (s, 2H), 2.05 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 350.2 (M + H).sup.+ 214 122 VI.29 [01015] .sup.1H NMR (400 MHz, DMSO-d6) δ 13.45 (bs, 1H), 8.59 (d, J = 3.6 Hz, 1H), 8.09 (d, J = 6.8 Hz, 1H), 7.36-7.30 (m, 3H), 7.16-7.11 (m, 2H), 7.07 (d, J = 8.4 Hz, 2H), 6.90 (d, J = 7.6 Hz, 2H), 4.39 (s, 2H), 2.03 (s, 3H), 1.81 (s, 6H), 1.71 (s, 6H). LC- MS: m/z 473.2 (M + H).sup.+ 215 123 XV.9 [01016] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.39 (s, 1H), 7.94 (s, 1H), 7.39 (d, J = 2.0 Hz, 1H), 7.33- 7.24 (m, 4H), 6.92 (d, J = 8.8 Hz, 2H), 4.20-3.99 (m, 1H), 3.98-3.62 (m, 1H), 3.10-2.92 (m, 2H), 2.45-2.37 (m, 1H), 2.06 (s, 3H), 2.01-1.97 (m, 1H), 1.85 (s, 6H), 1.73 (s, 6H), 1.69-1.55 (m, 2H), 1.44-1.39 (m, 1H). LC- MS: m/z 493.2 (M + H).sup.+ 217 124 VI.30 [01017] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.15 (bs, 1H), 7.52 (s, 1H), 7.32 (s, 1H), 7.18 (s, 3H), 7.02 (d, J = 8.8 Hz, 2H), 6.93 (d, J = 8.4 Hz, 2H), 6.84- 6.82 (m, 1H), 6.12-6.10 (m, 1H), 5.44 (s, 2H), 2.04 (s, 3H), 1.82 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 461.2 (M + H).sup.+ 218 125 VI.31 [01018] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.41 (s, 1H), 8.33 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 4.8 Hz, 1H), 7.75 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 7.2 Hz, 1H), 7.42 (s, 1H), 7.31 (s, 1H), 7.17 (s, 2H), 6.94 (d, J = 8.8 Hz, 2H), 6.89- 6.86 (m, 3H), 3.32 (s, 3H), 2.04 (s, 3H), 1.82 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 488.1 (M + H).sup.+ 219 126 VI.32 [01019] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.89 (s, 1H), 7.43 (d, J = 8.4 Hz, 1H), 7.28 (s, 2H), 7.20 (d, J = 3.2 Hz, 1H), 7.09 (S, 3H), 6.86 (dd, J.sub.1 = 1.6 Hz, J.sub.2 = 8.4 Hz, 1H), 6.36 (d, J = 2.8 Hz, 1H), 4.9 (s, 2H), 2.04 (s, 3H), 1.81 (s, 6H), 1.71 (s, 6H). LC-MS: m/z 435.2 (M + H).sup.+ 220 127 VI.33 [01020] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.00 (bs, 1H), 7.82 (d, J = 6.4 Hz, 2H), 7.67 (s, 1H), 7.34 (s, 1H), 7.21-7.17 (m, 3H), 6.89 (d, J = 5.6 Hz, 2H), 6.74 (d, J = 7.6 Hz, 1H), 5.16 (s, 2H), 2.05 (s, 3H), 1.84 (s, 6H), 1.73 (s, 6H). LC-MS: m/z 462.3 (M + H).sup.+ 221 128 VI.34 [01021] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.75 (bs, 1H), 8.03 (s, 1H), 7.62 (d, J = 2.8 Hz, 2H), 7.33 (d, J = 1.2 Hz, 1H), 7.19- 7.15 (m, 3H), 6.88-6.86 (m, 1H), 6.78 (s, 1H), 6.61-6.56 (m, 1H), 5.46 (s, 2H), 2.05 (s, 3H), 1.84 (s, 6H), 1.73 (s, 6H). LC- MS: m/z 462.2 (M + H).sup.+ 226 129 XII.25 [01022] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.5 (bs, 1H), 8.38 (s, 1H), 8.18 (d, J = 7.6 Hz, 1H), 8.11 (d, J = 3.6 Hz, 1H), 7.41 (d, J = 2.0 Hz, 1H), 7.34 (dd, J.sub.1 = 1.6 Hz, J.sub.2 = 7.6 Hz, 1H), 7.10 (d, J = 8.0 Hz, 1H), 6.74 (dd, J.sub.1 = 4.8 Hz, J.sub.2 = 7.2 Hz, 1H), 5.38 (s, 2H), 2.04 (s, 3H), 1.84 (d, J = 2.4 Hz, 6H), 1.69 (s, 6H). LC-MS: m/z 464.2 (M + H).sup.+ 227 130 VI.35 [01023] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.9 (s, 1H), 7.32-7.26 (m, 3H), 7.09- 7.07 (m, 2H), 6.95 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 8.4 Hz, 1H), 6.93 (d, J = 7.2 Hz, 1H), 6.35 (d, J = 2.4 Hz, 1H), 4.97 (s, 2H), 2.03 (s, 3H), 1.80 (s, 6H), 1.71 (s, 6H). LC-MS: m/z 435.2 (M + H).sup.+ 228 131 XII.26 [01024] .sup.1H NMR (400 MHz, DMSO-d6) δ 13.4 (bs, 1H), 10.2 (s, 1H), 8.40- 8.30 (m, 2H), 7.40-7.39 (m, 2H), 7.38-7.30 (m, 1H), 699-6.90 (m, 2H), 6.90-6.80 (m, 1H), 6.80- 6.70 (m, 1H), 4.30 (s, 2H), 3.36 (m, 2H), 2.9 (m, 2H), 2.05 (s, 3H), 1.85 (d, J = 2.4 Hz, 6H), 1.73 (s, 6H). LC- MS: m/z 514.2 (M + H) 233 132 XX.2 [01025] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.53 (bs, 1H), 8.35 (dd, J.sub.1 = 1.9 Hz, J.sub.2 = 4.4 Hz, 1H), 7.83 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 7.8 Hz, 1H), 7.43 (d, J = 2.4 Hz, 1H), 7.34 (dd, J.sub.1 = 1.9 Hz, J.sub.2 = 8.8 Hz, 1H), 7.23 (d, J = 8.4 Hz, 1H), 7.0-6.92 (m, 2H), 6.3 (dd, J.sub.1 = 1.9 Hz, J.sub.2 = 8.3 Hz, 1H), 6.1 (dd, J.sub.1 = 1.9 Hz, J.sub.2 = 8.3 Hz, 1H), 6.04 (d, J = 2.5 Hz, 1H), 3.34 (s, 3H), 3.07 (s, 3H), 2.06 (s, 3H), 1.86 (s, 6H), 1.74 (s, 6H). LC-MS: m/z 502.3 (M + H).sup.+ 236 133 XX.3 [01026] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.60 (bs, 1H), 8.30 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 4.9 Hz, 1H), 7.82 (dd, J.sub.1 = 1.5 Hz, J.sub.2 = 7.4 Hz, 1H), 7.71 (s, 1H), 7.38 (d, J = 2.9 Hz, 2H), 7.32 (dd, J.sub.1 = 1.9 Hz, J.sub.2 = 8.3 Hz, 1H), 6.88 (m, 2H), 5.27 (s, 2H), 3.25 (s, 2H), 2.08 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 477.2 (M + H).sup.+ 240 134 XII.27 [01027] .sup.1H NMR (400 MHz, DMSO-d6) δ 13.82-13.2 (bs, 1H), 10.44 (s, 1H), 8.37 (dd, J.sub.1 = 1.6 Hz, J.sub.2 = 4.4 Hz, 1H), 8.19 (dd, J.sub.1 = 1.6 Hz, J.sub.2 = 7.6 Hz, 1H), 7.60 (d, J = 1.6 Hz, 1H), 7.42 (dd, J.sub.1 = 1.6 Hz, J.sub.2 = 8.0 Hz, 2H), 7.34 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 8.4 Hz, 1H), 7.11 (d, J = 8.4 Hz, 1H), 6.78 (dd, J.sub.1 = 4.8 Hz, J.sub.2 = 8.0 Hz, 1H), 5.26 (s, 2H), 2.04 (s, 3H), 1.82 (d, J = 6.8 Hz, 6H), 1.71 (s, 6H). LC-MS: m/z 463.2 (M + H).sup.+ 241 135 VI.38 [01028] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.61 (s, 1H), 8.39 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 4.8 Hz, 1H), 7.89 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 7.6 Hz, 1H), 7.46 (s, 1H), 7.29 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 8.4 Hz, 2H), 7.16 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 8.4 Hz, 1H), 7.07- 6.98 (m, 2H), 6.61 (t, J = 8.4 Hz, 2H), 6.41 (t, J = 1.6 Hz, 1H), 3.36 (s, 3H), 2.04 (s, 3H), 1.82 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 488.1 (M + H).sup.+ 243 136 VI.39 [01029] .sup.1H NMR (400 MHz, DMSO-d6) δ 13.2 (bs, 1H), 8.23 (s, 1H), 8.13 (d, J = 6.9 Hz, 1H), 7.52 (s, 1H), 7.33 (s, 1H), 7.19 (m, 3H), 7.04 (d, J = 8.8 Hz, 2H), 6.98 (d, J = 8.8 Hz, 2H), 2.04 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 475.1 244 137 XIII.10 [01030] .sup.1H NMR (400 MHz, DMSO-d6) δ 8.59 (dd, J.sub.1 = 1.6 Hz, J.sub.2 = 4.4 Hz, 1H), 8.22 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 8.0 Hz, 1H), 7.49 (dd, J.sub.1 = 4.8 Hz, J.sub.2 = 8.0 Hz, 1H), 7.20 (d, J = 2.0 Hz, 1H), 7.12 (dd, J.sub.1 = 2.4 Hz, J.sub.2 = 8.8 Hz, 1H), 6.69 (d, J = 8.8 Hz, 1H), 5.26 (d, J = 7.2 Hz, 1H), 4.45 (s, 2H), 4.24-4.20 (m, 1H), 3.36-3.20 (m 2H), 3.10- 3.02 (m, 2H), 2.36-2.32 (m, 1H), 2.02 (s, 3H), 1.78 (s, 6H), 1.67 (s, 6H). LC-MS: m/z 466.20 (M + H).sup.+ 245 138 VI.40 [01031] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.8-12.0 (bs, 1H), 8.2 (s, 1H), 7.87 (s, 1H), 7.67 (d, J = 5.6 Hz, 1H), 7.17 (d, J = 8.8 Hz, 2H), 6.95-6.89 (m, 4H), 6.85-6.82 (m, 3H), 3.3 (s, 3H), 2.03 (s, 3H), 1.82 (s, 6H), 1.71 (s, 6H). LC-MS: m/z 454.1 (M + H).sup.+ 246 139 XX.4 [01032] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.49 (s, 1H), 8.34 (s, 1H), 7.77- 7.76 (m, 1H), 7.24-7.22 (m, 2H), 6.93-6.87 (m, 7H), 3.19 (s, 3H), 2.04 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 468.1 (M + H).sup.+ 247 140 XX.5 [01033] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.57 (s, 1H), 8.36 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 4.9 Hz, 1H), 7.86 (dd, J.sub.1 = 1.4 Hz, J.sub.2 = 7.3 Hz, 1H), 7.23 (d, J = 8.3 Hz, 2H), 7.09 (d, J = 8.4 Hz, 1H), 6.95 (m, 3H), 6.5 (m, 2H), 6.39 (t, J = 2.4 Hz, 1H), 3.35 (s, 3H), 3.16 (s, 3H), 2.04 (bs, 3H), 1.82 (s, 6H), 1.69 (s, 6H). LC-MS: m/z 468.1 (M + H).sup.+ 248 141 XIII.11 [01034] .sup.1H NMR (400 MHz, DMSO-d6) δ 10.80- 12.80 (bs, 1H), 8.54 (d, J = 3.4 Hz, 1H), 8.14 (d, J = 6.8 Hz, 1H), 7.42 (m, 1H), 7.16 (d, J = 2.4 Hz, 1H), 7.09 (dd, J1 = 1.9 Hz, J2 = 8.3 Hz, 1H), 6.67 (d, J = 8.8 Hz, 1H), 4.87 (d, J = 8.0 Hz, 1H), 4.16 (m, 2H), 3.57 (bs, 1H), 2.98 (d, J = 9.2 Hz, 1H), 2.7 (m, 1H), 2.57 (m, 3H), 2.08 (s, 3H), 1.82-1.77 (m, 9H), 1.73 (m, 7H), 1.58-1.49 (m, 3H). LC- MS: m/z 480.1 (M + H).sup.+ 249 142 XII.28 [01035] .sup.1H NMR (400 MHz, DMSO-d6) δ 13.4 (bs, 1H), 10.6 (bs, 1H), 8.22- 8.21 (m, 1H), 8.16 (dd, J.sub.1 = 1.6 Hz, J.sub.2 = 7.2 Hz, 1H), 7.47-7.38 (m, 4H), 7.27 (d, J = 8.4 Hz, 1H), 6.72 (dd, J.sub.1 = 4.4 Hz, J.sub.2 = 7.6 Hz, 1H), 6.52 (d, J = 8.8 Hz, 2H), 3.17 (s, 3H), 2.07 (s, 3H), 1.89 (s, 6H), 1.74 (s, 6H). LC-MS: m/z 487.2 (M + H).sup.+ 250 143 VI.42 [01036] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.80 (s, 1H), 9.80 (s, 1H), 7.88 (s, 1H), 7.39 (d, J = 1.4 Hz, 1H), 7.33-7.27 (m, 4H), 6.98 (d, J = 8.3 Hz, 2H), 4.20-4.17 (bs, 2H), 3.49- 3.42 (m, 1H), 2.85-2.70 (m, 3H), 2.06 (s, 3H), 1.91-1.85 (m, 7H), 1.84- 1.72 (m, 8H), 1.57-1.40 (m, 1H). LC-MS: m/z 479.1 (M + H).sup.+2 252 144 VI.43 [01037] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.72 (s, 1H), 7.99 (s, 1H), 7.96 (d, J = 1.6 Hz, 1H), 7.80 (dd, J.sub.1 = 1.6 Hz, J.sub.2 = 7.6 Hz, 1H), 7.68-7.61 (m, 2H), 7.42-7.35 (m, 3H), 7.29 (d, J = 2.0 Hz, 1H), 7.17 (dd, J.sub.1 = 2.4 Hz, J.sub.2 = 8.8 Hz, 1H), 3.30 (s, 3H), 2.08 (s, 3H), 1.82 (s, 6H), 1.71 (s, 6H). LC-MS: m/z 487.1 (M − H).sup.+ 254 145 XV.11 [01038] .sup.1H NMR (400 MHz, DMSO-d6) δ 13.72 (bs, 1H), 10.74 (bs, 1H), 10.02 (s, 1H), 8.46 (dd, J.sub.1 = 1.9 Hz, J.sub.2 = 5.0 Hz, 1H), 8.30 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 7.8 Hz, 1H), 7.95 (d, J = 8.8 Hz, 2H), 7.88 (d, J = 8.8 Hz, 2H), 7.69 (d, J = 8.8 Hz, 2H), 7.32 (d, J = 8.8 Hz, 2H), 6.96 (m, 1H), 2.06 (s, 3H), 1.87 (s, 6H), 1.74 (s, 6H). LC-MS: m/z 468.1 (M + H).sup.+ 255 146 XV.12 [01039] .sup.1H NMR (400 MHz, DMSO-d6) δ 13.00-12.8 (bs, 1H), 9.77 (s, 1H), 7.85 (d, J = 6.4 Hz, 1H), 7.77 (d, J = 8.8 Hz, 2H), 7.66-7.64 (m, 3H), 7.50- 7.42 (m, 1H), 7.36 (d, J = 8.0 Hz, 1H), 7.28 (d, J = 8.8 Hz, 2H), 6.52 (d, J = 8.8 Hz, 2H), 3.26 (s, 3H), 2.05 (s, 3H), 1.85 (s, 6H), 1.73 (s, 6H). LC-MS: m/z 481.1 (M + H).sup.+ 258 147 XV.13 [01040] .sup.1H NMR (400 MHz, DMSO-d6) δ 9.87 (s, 1H), 8.43 (bs, 1H), 7.95 (d, J = 6.9 Hz, 1H), 7.80 (d, J = 8.8 Hz, 2H), 7.67 (d, J = 8.8 Hz, 2H), 7.29 (d, J = 8.3 Hz, 2H), 7.19 (m, 1H), 6.82 (d, J = 8.3 Hz, 2H), 3.38 (s, 3H), 2.05 (s, 3H), 1.86 (s, 6H), 1.73 (s, 6H). LC-MS: m/z 482.25 (M + H).sup.+ 259 148 XV.14 [01041] .sup.1H NMR (400 MHz, DMSO-d6) δ 13.00 (bs, 1H), 9.93 (s, 1H), 9.71 (s, 1H), 8.03 (d, J = 8.8 Hz, 2H), 7.94 (d, J = 8.8 Hz, 2H), 7.79 (m, 1H), 7.70 (d, J = 8.8 Hz, 2H), 7.51 (d, J = 7.3 Hz, 1H), 7.31 (d, J = 8.8 Hz, 2H), 7.12 (d, J = 8.3 Hz, 1H), 2.06 (s, 3H), 1.83 (s, 6H), 1.74 (s, 6H). LC-MS: m/z 468.20 (M + H).sup.+ 260 149 XX.6 [01042] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.00-11.8 (bs, 1H), 7.65 (d, J = 8.0 Hz, 2H), 7.5 (d, J = 8.4 Hz, 1H), 7.4-7.35 (m, 1H), 7.32-7.2 (m, 1H), 7.25-7.15 (m, 3H), 6.86 (d, J = 8.4 Hz, 2H), 6.42 (bs, 2H), 3.16 (s, 3H), 3.07 (s, 3H), 2.02 (s, 3H), 1.78 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 495.2 (M + H).sup.+ 261 150 XII.29 [01043] .sup.1H NMR (400 MHz, DMSO-d6) δ 10.4 (bs, 1H), 7.62 (t, J = 8.0 Hz, 1H), 7.54 (s, 1H), 7.34-7.31 (m, 3H), 7.24 (dd, J.sub.1 = 1.2 Hz, J.sub.2 = 8.4 Hz, 1H), 7.17- 7.09 (m, 2H), 7.04 (s, 1H), 6.97 (d, J = 7.2 Hz, 1H), 6.63 (d, J = 8.4 Hz, 1H), 2.05 (s, 3H), 1.84 (s, 6H), 1.73 (s, 6H). LC-MS: m/z 474.1 (M + H).sup.+ 263 151 XII.31 [01044] .sup.1H NMR (400 MHz, DMSO-d6) δ 13.2 (bs, 1H), 11.67 (s, 1H), 9.07 (s, 1H), 8.52 (d, J = 2.0 Hz, 1H), 8.28 (d, J = 2.4 Hz, 1H), 7.60 (s, 1H), 7.51-7.45 (m, 3H), 7.34 (s, 1H), 7.22 (s, 1H), 1.91 (s, 2H), 1.72-1.64 (m, 13H). LC-MS: m/z 506.0 (M + H).sup.+ 266 152 XX.7 [01045] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.8 (bs, 1H), 8.43 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 4.4 Hz, 1H), 7.96 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 7.6 Hz, 1H), 7.30 (d, J = 8.8 Hz, 2H), 7.08-7.04 (m, 3H), 6.59-6.58 (m, 2H), 6.37 (s, 1H), 3.37 (s, 3H), 3.2 (s, 3H), 2.06 (s, 3H), 1.83 (d, J = 2.4 Hz, 6H), 1.73 (s, 6H). LC-MS: m/z 536.1 (M + H).sup.+ 267 153 XII.32 [01046] .sup.1H NMR (400 MHz, DMSO-d6) δ 13.4 (bs, 1H), 8.83 (s, 1H), 8.54 (dd, J.sub.1 = 0.8 Hz, J.sub.2 = 12.0 Hz, 2H), 8.14 (s, 1H), 7.91 (s, 1H), 7.41 (d, J = 2.0 Hz, 1H), 7.35-7.28 (m, 2H), 6.84 (s, 1H), 6.73 (d, J = 13.6 Hz, 2H), 2.05 (s, 3H), 1.84 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 542.2 (M + H).sup.+ 268 154 XII.24 [01047] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.80 (bs, 1H), 11.58 (s, 1H), 9.5 (s, 1H), 7.6 (t, J = 7.2 Hz, 2H), 7.49-7.43 (m, 5H), 6.63 (d, J = 8.4 Hz, 1H), 1.99 (s, 3H), 1.72-1.60 (m, 12H). LC-MS: m/z 506.2 (M + H).sup.+ 270 155 XX.8 [01048] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.8 (bs, 1H), 7.80 (m, 1H), 7.60 (m, 1H), 7.29 (m, 4H), 6.83 (t, J = 9.3 Hz, 4H), 6.57 (d, J = 8.8 Hz, 2H), 3.19 (s, 3H), 2.04 (s, 3H), 1.82 (s, 6H), 1.71 (s, 6H). LC-MS: m/z (M + H).sup.+ LC-MS: m/z 454.1 (M + H).sup.+ 271 156 XX.9 [01049] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.91 (s, 1H), 8.52 (dd, J.sub.1 = 1.6 Hz, J.sub.2 = 4.4 Hz, 1H), 8.03 (dd, J.sub.1 = 1.6 Hz, J.sub.2 = 7.2 Hz, 1H), 7.21-7.16 (m, 4H), 7.12 (d, J = 8.8 Hz, 2H), 6.44 (d, J = 8.8 Hz, 2H), 3.44 (s, 3H), 3.06 (s, 3H), 2.02 (s, 3H), 1.79 (s, 6H), 1.67 (s, 6H). LC-MS: m/z 536.1 (M + H).sup.+ 272 157 XV.15 [01050] .sup.1H NMR (400 MHz, DMSO-d6) δ 13.00 (bs, 1H), 10.16 (s, 1H), 9.6 (bs, 1H), 7.89 (m, 3H), 7.77 (d, J = 9.3 Hz, 2H), 7.51 (d, J = 8.4 Hz, 2H), 7.38 (m, 1H), 7.23 (d, J = 8.8 Hz, 2H), 7.14 (d, J = 8.8 Hz, 1H), 6.74 (m, 1H), 2.08 (s, 3H), 1.90 (s, 6H), 1.76 (s, 6H). LC-MS: m/z 467.1 (M + H).sup.+ 273 158 XX.10 [01051] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.9 (bs, 1H), 7.85 (dd, J.sub.1 = 1.2 Hz, J.sub.2 = 8.8 Hz, 1H), 7.70- 7.66 (m, 1H), 7.46-7.39 (m, 2H), 7.10-7.04 (m, 3H), 6.78-6.73 (m, 2H), 6.39 (d, J = 8.8 Hz, 2H), 3.31 (s, 3H), 3.02 (s, 3H), 2.02 (s, 3H), 1.74 (s, 6H), 1.67 (s, 6H). LC-MS: m/z 535.1 (M + H).sup.+ 274 159 XV.16 [01052] .sup.1H NMR (400 MHz, DMSO-d6) δ 13.15 (s, 1H), 9.71 (s, 1H), 7.94- 7.91 (m, 1H), 7.46-7.42 (m, 1H), 7.34-7.25 (m, 5H), 6.85 (t, J = 7.2 Hz, 1H), 1.56-1.48 (m, 5H), 1.33-1.12 (m, 6H), 0.92- 0.74 (m, 7H). LC-MS: m/z 369.1 (M + H).sup.+ 275 160 XX.11 [01053] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.72 (s, 1H), 7.68-7.65 (m, 2H), 7.53 (t, J = 8.4 Hz, 1H), 7.30 (d, J = 8.8 Hz, 2H), 7.26-7.19 (m, 2H), 7.09 (d, J = 8.8 Hz, 2H), 6.88 (dd, J.sub.1 = 3.2 Hz, J.sub.2 = 8.8 Hz, 1H), 6.55 (d, J = 9.6 Hz, 1H), 3.29 (s, 3H), 3.18 (s, 3H), 2.05 (s, 3H), 1.85 (s, 6H), 1.73 (s, 6H). LC-MS: m/z 468.1 (M + H).sup.+ 276 161 XX.12 [01054] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.79 (s, 1H), 7.79 (dd, J.sub.1 = 1.5 Hz, J.sub.2 = 7.3 Hz, 1H), 7.62 (t, J = 1.5 Hz, 1H), 7.35 (m, 2H), 7.14 (d, J = 8.8 Hz, 2H), 6.98 (d, J = 8.8 Hz, 2H), 6.63 (d, J = 8.8 Hz, 2H), 6.57 (d, J = 9.3 Hz, 2H), 3.26 (m, 1H), 3.20 (s, 3H), 3.18 (s, 3H), 1.48 (m, 4H), 1.23 (m, 4H), 0.83 (m, 6H). LC-MS: m/z 488.7 (M + H).sup.+ 277 162 XX.13 [01055] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.79 (s, 1H), 7.78 (d, J = 7.6 Hz, 1H), 7.60-7.59 (m, 1H), 7.37-7.25 (m, 4H), 7.17- 7.14 (m, 1H), 7.08-7.00 (m, 5H), 6.72 (d, J = 8.8 Hz, 2H), 6.59 (d, J = 8.8 Hz, 2H), 3.2 (s, 6H), 3.08-3.04 (m, 1H), 1.1 (d, J = 6.8 Hz, 6H). LC-MS: m/z 451.1 (M + H).sup.+ 278 163 [01056] LC-MS: m/z 495.2 (M + H).sup.+ 279 164 [01057] LC-MS: m/z 523.6 (M + H).sup.+ 282 165 [01058] LC-MS: m/z 453.1 (M + H).sup.+ 284 166 XII.36 [01059] .sup.1H NMR (400 MHz, DMSO-d6) δ 11.90 (bs, 1H), 7.88 (d, J = 7.4 Hz, 1H), 7.46 (s, 1H), 7.30 (d, J = 2.4 Hz, 1H), 7.11 (m, 4H), 6.91 (m, 4H), 6.63 (m, 1H), 2.05 (s, 3H), 1.85 (s, 6H), 1.72 (s, 6H). LC-MS: 474.0 (M + H).sup.+ 285 167 XV.17 [01060] .sup.1H NMR (400 MHz, DMSO-d6) δ 13.2 (bs, 1H), 9.90 (bs, 1H), 7.93 (d, J = 8.0 Hz, 1H), 7.77 (d, J = 8.8 Hz, 2H), 7.45- 7.43 (m, 2H), 7.36 (d, J = 7.6 Hz, 1H), 7.30 (d, J = 8.8 Hz, 2H), 6.86 (t, J = 7.2 Hz, 1H), 2.07 (s, 9H), 1.66 (s, 6H). LC- MS: m/z 391.0 (M + H).sup.+ 286 168 XX.14 [01061] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.7 (bs, 1H), 7.75 (dd, J.sub.1 = 1.6 Hz, J.sub.2 = 8.0 Hz, 1H), 7.61- 7.57 (m, 1H), 7.43 (d, J = 2.0 Hz, 1H), 7.43-7.23 (m, 3H), 6.81 (t, J = 9.2 Hz, 3H), 6.57 (d, J = 8.8 Hz, 2H), 3.19 (s, 3H), 2.04 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 488.0 (M + H).sup.+ 287 169 VI.46 [01062] .sup.1H NMR (400 MHz, DMSO-d6) δ 13.60- 12.00 (bs, 1H), 9.50 (s, 1H), 8.34 (s, 1H), 7.87 (dd, J.sub.1 = 1.2 Hz, J.sub.2 = 8.0 Hz, 1H), 7.36-7.03 (m, 10H), 6.70 (t, J = 7.2 Hz, 1H), 4.06-4.02 (m, 2H), 2.88-2.83 (m, 3H), 1.68- 1.55 (m, 4H), 1.33-1.10 (m, 5H), 0.89 (t, J = 7.2 Hz, 6H). LC-MS: m/z 444.1 (M + H).sup.+ 288 170 XV.18 [01063] .sup.1H NMR (400 MHz, DMSO-d6) δ 13.2 (bs, 1H), 11.9 (bs, 1H), 10.38 (bs, 1H), 9.8 (s, 1H), 7.96 (m, 4H), 7.7 (bs, 1H), 7.47 (m, 2H), 7.36 (m, 2H), 6.92 (m, 1H), 6.6 (bs, 1H), 3.44 (m, 4H), 1.53 (m, 4H), 1.27 (m, 4H), 0.84 (m, 6H). LC-MS: m/z 460.1 (M + H).sup.+ 289 71 XII.37 [01064] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.85 (bs, 1H), 7.77 (dd, J.sub.1 = 1.2 Hz, J.sub.2 = 8.0 Hz, 1H), 7.61- 7.57 (m, 1H), 7.35-7.32 (m, 1H), 7.28 (d, J = 8.0 Hz, 1H), 7.13 (d, J = 8.4 Hz, 2H), 6.88 (d, J = 9.6 Hz, 2H), 6.67 (d, J = 8.8 Hz, 2H), 6.55 (d, J = 6.8 Hz, 2H), 3.66-3.61 (m, 2H), 3.13 (s, 3H), 2.03 (s, 3H), 1.79 (s, 6H), 1.71 (s, 6H), 1.13 (t, J = 7.6 Hz, 3H). LC-MS: m/z 481.1 (M + H).sup.+ 290 172 XII.38 [01065] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.8 (bs, 1H), 9.48 (s, 1H), 7.87 (dd, J.sub.1 = 1.2 Hz, J.sub.2 = 7.6 Hz, 1H), 7.35 (t, J = 6.8 Hz, 1H), 7.26 (d, J = 8.8 Hz, 2H), 7.15 (d, J = 8.8 Hz, 2H), 7.05 (d, J = 8.8 Hz, 1H), 6.99-6.94 (m, 4H), 6.70 (t, J = 7.2 Hz, 1H), 3.23 (s, 3H), 2.05 (s, 3H), 1.84 (s, 6H), 1.78 (s, 6H). LC-MS: m/z 453.1 (M + H).sup.+ 291 173 VI.47 [01066] .sup.1H NMR (400 MHz, DMSO-d6) δ 13.2 (s, 1H), 8.48 (s, 1H), 7.83 (d, J = 7.2 Hz, 1H), 7.70- 7.65 (m, 3H), 7.31-7.25 (m, 3H), 7.16-7.13 (m, 4H), 3.84 (s, 3H), 2.06 (s, 3H), 1.86 (s, 6H), 1.74 (s, 6H). LC-MS: m/z 478.1 (M + H).sup.+ 292 174 VI.48 [01067] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.91 (s, 1H), 9.40 (s, 1H), 8.09 (s, 1H), 7.87 (d, J = 1.4 Hz, 1H), 7.33 (t, J = 6.8 Hz, 1H), 7.15-7.08 (m, 8H), 7.01-6.98 (m, 3H), 6.70- 6.65 (m, 4H), 3.58 (t, J = 7.8 Hz, 2H), 1.58-1.51 (m, 2H), 1.38-1.28 (m, 2H), 0.88 (t, J = 7.3 Hz, 3H), LC-MS: m/z 452.1 (M + H).sup.+ 293 175 XV.19 [01068] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.99 (bs, 1H), 9.50 (bs, 1H), 8.36 (s, 1H), 7.88 (dd, J.sub.1 = 1.4 Hz, J.sub.2 = 7.8 Hz, 1H), 7.36 (t, 1H), 7.21-7.13 (m, 6H), 7.06-7.01 (m, 3H), 6.70 (t, J = 7.8 Hz, 1H), 3.30 (m, 4H), 1.52-1.49 (m, 4H), 1.23 (m, 4H), 0.86-0.84 (m, 6H). LC- MS: m/z 460.1 (M + H).sup.+ 294 176 XV.20 [01069] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.95 (s, 1H), 9.5 (s, 1H), 8.45 (s, 1H), 7.88 (dd, J.sub.1 = 1.6 Hz, J.sub.2 = 8.0 Hz, 1H), 7.67 (d, J = 8.8 Hz, 2H), 7.35 (t, J = 1.6 Hz, 1H), 7.23 (s, 1H), 7.20-7.14 (m, 4H), 7.07 (d, J = 8.4 Hz, 1H), 6.99 (d, J = 8.8 Hz, 2H), 6.73-6.69 (m, 1H), 2.06 (s, 9H), 1.65 (s, 6H). LC- MS: m/z 482.1 (M + H).sup.+ 295 177 VI.49 [01070] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.83 (bs, 1H), 9.42 (s, 1H), 7.99 (s, 1H), 7.85 (dd, J.sub.1 = 1.6 Hz, J.sub.2 = 7.6 Hz, 1H), 7.32 (t, J = 8.8 Hz, 1H), 7.20 (d, J = 8.8 Hz, 2H), 7.11-7.04 (m, 4H), 7.01-6.96 (m, 3H), 6.67 (t, J = 7.6 Hz, 1H), 2.13-2.12 (m, 1H), 1.66 (s, 2H), 1.50-1.32 (m, 8H), 1.17 (s, 2H), 0.85 (s, 6H). LC-MS: m/z 467.1 (M + H).sup.+ 296 178 XX.15 [01071] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.79 (s, 1H), 7.75 (d, J = 8.0 Hz, 1H), 7.58 (t, J = 6.8 Hz, 1H), 7.33-7.29 (m, 2H), 7.11 (d, J = 8.8 Hz, 2H), 6.89 (d, J = 8.8 Hz, 2H), 7.67 (d, J = 8.8 Hz, 2H), 7.01 (d, J = 8.8 Hz, 2H), 3.18 (s, 3H), 3.12 (s, 3H), 2.10 (m, 1H), 1.62 (s, 2H), 1.46-1.30 (m, 8H), 1.16 (s, 2H), 0.83 (s, 6H). LC-MS: m/z 495.1 (M + H).sup.+ 297 179 XV.21 [01072] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.84 (bs, 1H), 10.04 (s, 1H), 9.23 (s, 1H), 7.89 (d, J = 8.3 Hz, 2H), 7.78 (d, J = 8.3 Hz, 2H), 7.67 (m, 3H), 7.51 (d, J = 8.3 Hz, 2H), 7.40 (d, J = 6.8 Hz, 1H), 7.01 (d, J = 8.3 Hz, 1H), 2.08 (s, 3H), 1.91 (s, 6H), 1.76 (s, 6H). LC-MS: m/z 468.0 (M + H).sup.+ 298 180 XI.17 [01073] .sup.1H NMR (400 MHz, DMSO-d6) δ 13.4 (bs, 1H), 10.27 (s, 1H), 8.51 (d, J = 13.6 Hz, 2H), 8.34 (s, 1H), 8.21 (d, J = 6.8 Hz, 1H), 7.58 (d, J = 7.2 Hz, 2H), 7.40-7.35 (m, 4H), 7.25 (d, J = 7.2 Hz, 2H), 6.81 (bs, 1H), 2.04 (s, 3H), 1.84 (s, 6H), 1.73 (s, 6H). LC-MS: m/z 483.1 (M + H).sup.+ 299 181 XIX.3 [01074] .sup.1H NMR (400 MHz, DMSO-d6) δ 13.80- 12.80 (bs, 1H), 10.05 (bs, 1H), 9.86 (s, 1H), 8.25 (d, J = 2.8 Hz, 1H), 8.15 (d, J = 7.2 Hz, 1H), 7.53 (d, J = 8.4 Hz, 2H), 7.34 (d, J = 8.8 Hz, 2H), 7.27 (d, J = 8.0 Hz, 2H), 6.71 (dd, J.sub.1 = 4.8 Hz, J.sub.2 = 8.0 Hz, 1H), 6.58 (d, J = 8.8 Hz, 2H), 5.85 (bs, 1H), 3.82 (bs, 2H), 2.04 (s, 3H), 1.82 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 497.1 (M + H).sup.+ 300 182 XIX.1 [01075] .sup.1H NMR (400 MHz, DMSO-d6) δ 13.00 (bs, 1H), 9.13 (s, 1H), 8.50 (s, 1H), 8.43 (s, 1H), 7.68 (m, 3H), 7.37 (m, 5H), 7.25 (d, J = 8.3 Hz, 2H), 6.98 (d, J = 8.3 Hz, 1H), 2.05 (s, 3H), 1.76 (s, 6H), 1.73 (s, 6H). LC-MS: m/z 483.1 (M + H).sup.+ 301 183 XV.22 [01076] .sup.1H NMR (400 MHz, DMSO-d6) δ 9.76 (bs, 1H), 8.32 (bs, 1H), 8.25 (m, 1H), 7.95 (d, J = 8.8 Hz, 2H), 7.89 (d, J = 8.8 Hz, 2H), 7.54 (d, J = 8.3 Hz, 1H), 7.45 (s, 1H), 7.37 (m, 1H), 6.86 (m, 1H), 2.07 (s, 3H), 1.88 (s, 6H), 1.74 (s, 6H). LC-MS: m/z 502.0 (M + H).sup.+ 302 184 XV.23 [01077] .sup.1H NMR (400 MHz, DMSO-d6) δ 14.00- 13.00 (bs, 1H), 10.36 (s, 1H), 10.02 (s, 1H), 8.36 (m, 1H), 8.24 (d, J = 7.8 Hz, 1H), 7.65 (d, J = 8.3 Hz, 2H), 7.52 (d, J = 8.8 Hz, 2H), 7.28-7.25 (m, 4H), 6.86-6.83 (m, 1H), 3.56 (s, 2H), 2.03 (s, 3H), 1.82 (s, 6H), 1.71 (s, 6H). LC-MS: m/z 482.1 (M + H).sup.+ 303 185 XV.24 [01078] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.93 (bs, 1H), 9.91 (s, 1H), 8.81 (s, 1H), 7.88 (d, J = 8.8 Hz, 2H), 7.75 (s, 1H), 7.68 (d, J = 8.8 Hz, 2H), 7.48- 7.39 (m, 3H), 7.30 (d, J = 8.8 Hz, 2H), 7.14 (d, J = 8.0 Hz, 2H), 2.05 (s, 3H), 1.86 (s, 6H), 1.73 (s, 6H). LC-MS: m/z 467.1 (M + H).sup.+ 304 186 Int-VI [01079] .sup.1H NMR (400 MHz, DMSO-d6) δ 13.20 (bs, 1H), 9.66 (s, 1H), 7.90 (d, J = 8.4 Hz, 1H), 7.40- 7.38 (m, 3H), 7.26-7.24 (m, 5H), 7.20 (d, J = 8.4 Hz, 2H), 6.82 (t, J = 7.2 Hz, 1H), 2.04 (s, 3H), 1.84 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 507.1 (M + H).sup.+ 305 187 XX.16 [01080] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.80 (s, 1H), 7.75 (m, 1H), 7.59 (t, 1H), 7.32-7.30 (m, 2H), 7.12-7.08 (m, 2H), 6.93 (t, J = 8.3 Hz, 4H), 6.74 (d, J = 8.3 Hz, 2H), 6.64 (d, J = 7.3 Hz, 2H), 6.58 (d, J = 7.8 Hz, 3H), 3.56-3.54 (m, 2H), 3.19 (s, 3H), 3.16 (s, 3H), 1.51-1.49 (m, 2H), 1.33- 1.28 (m, 2H), 0.87 (t, J = 7.3 Hz, 3H), LC-MS: m/z 480.1 (M + H).sup.+ 306 188 XVIII.1 [01081] .sup.1H NMR (400 MHz, DMSO-d6) δ 13.79 (bs, 1H), 10.77 (s, 1H), 10.03 (s, 1H), 8.44-8.43 (m, 1H), 8.28 (dd, J.sub.1 = 1.6 Hz, J.sub.2 = 8.0 Hz, 1H), 7.89 (d, J = 8.4 Hz, 2H), 7.69 (d, J = 8.8 Hz, 2H), 7.19 (d, J = 8.8 Hz, 2H), 7.03-6.96 (m, 3H), 1.99 (s, 3H), 1.76 (s, 6H), 1.68 (s, 6H). LC-MS: m/z 504.0 (M + H).sup.+ 307 189 XIX.2 [01082] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.95 (bs, 1H), 9.50 (bs, 1H), 8.60 (s, 1H), 8.52 (s, 1H), 7.88 (d, J = 7.9 Hz, 1H), 7.46 (d, J = 8.3 Hz, 2H), 7.36 (m, 3H), 7.26 (d, J = 8.3 Hz, 2H), 7.17 (d, J = 8.8 Hz, 2H), 7.05 (d, J = 8.3 Hz, 1H), 6.70 (t, J = 7.4 Hz, 1H), 2.05 (s, 3H), 1.84 (s, 6H), 1.73 (s, 6H). LC-MS: m/z 482.0 (M + H).sup.+ 308 190 Int- XVIII [01083] .sup.1H NMR (400 MHz, DMSO-d6) δ 13.25 (bs, 1H), 10.02 (s, 1H), 9.75 (s, 1H), 7.92 (d, J = 8.0 Hz, 1H), 7.65 (d, J = 8.4 Hz, 2H), 7.49-7.41 (m, 2H), 7.28 (d, J = 8.4 Hz, 2H), 7.20 (d, J = 8.4 Hz, 2H), 7.02 (d, J = 8.4 Hz, 2H), 6.96 (t, J = 7.2 Hz, 1H), 2.00 (s, 3H), 1.77 (s, 6H), 1.69 (s, 6H). LC-MS: m/z 503.0 (M + H).sup.+ 309 191 VI.50 [01084] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.8 (s, 1H), 7.81 (d, J = 7.2 Hz, 1H), 7.66-7.62 (m, 1H), 7.41-7.32 (m, 6H), 7.27 (d, J = 8.8 Hz, 2H), 6.48 (d, J = 8.0 Hz, 2H), 3.22 (s, 3H), 2.05 (s, 3H), 1.85 (s, 6H), 1.73 (s, 6H). LC- MS: m/z 462.1 (M + H).sup.+ 310 192 XX.17 [01085] .sup.1H NMR (400 MHz, DMSO-d6) δ 13.2 (bs, 1H), 9.8 (bs, 1H), 7.9 (m, 1H), 7.40-7.30 (m, 1H), 7.27 (d, J = 8.4 Hz, 2H), 7.21-7.19 (m, 3H), 7.08 (d, J = 8.4 Hz, 2H), 7.02 (d, J = 8.4 Hz, 2H), 6.90- 6.80 (m, 1H), 3.34 (s, 3H), 2.02 (s, 3H), 1.81 (s, 6H), 1.70 (s, 6H). LC-MS: m/z 481.0 (M + H).sup.+ 311 193 XII.39 [01086] .sup.1H NMR (400 MHz, DMSO-d6) δ 10.40- 10.00 (bs, 1H), 7.57 (t, J = 8.0 Hz, 1H), 7.50-7.40 (m, 2H), 7.28 (d, J = 7.2 Hz, 1H), 7.20 (d, J = 8.8 Hz, 2H), 7.02 (d, J = 8.0 Hz, 2H), 6.95 (d, J = 8.4 Hz, 1H), 6.84 (d, J = 8.8 Hz, 2H), 3.22 (s, 3H), 2.04 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H). LC-MS: m/z m/z 454.0 (M + H).sup.+ 312 194 XVIII.2 [01087] .sup.1H NMR (400 MHz, DMSO-d6) δ 13.10 (bs, 1H), 9.97 (s, 1H), 9.76 (s, 1H), 7.97 (d, J = 8.8 Hz, 2H), 7.77 (t, J = 7.6 Hz, 1H), 7.64 (d, J = 8.8 Hz, 2H), 7.51 (d, J = 7.2 Hz, 1H), 7.19 (d, J = 8.8 Hz, 2H), 7.08 (d, J = 8.0 Hz, 1H), 7.02 (d, J = 8.4 Hz, 2H), 1.99 (s, 3H), 1.76 (s, 6H), 1.68 (s, 6H). LC-MS: m/z 504.2 (M + H).sup.+ 313 195 XV.25 [01088] .sup.1H NMR (400 MHz, DMSO-d6) δ 9.96 (s, 1H), 7.90 (t, J = 8.8 Hz, 3H), 7.70 (d, J = 8.8 Hz, 2H), 7.35 (m, 1H), 7.23- 7.21 (m, 1H), 7.19-7.15 (m, 4H), 7.02 (d, J = 8.8 Hz, 2H), 6.82-6.76 (m, 4H), 3.63 (t, J = 7.4 Hz, 2H), 1.53-1.51 (m, 2H), 1.35-1.31 (m, 2H), 0.86 (t, J = 7.3 Hz, 3H), LC-MS: m/z 480.2 (M + H).sup.+ 314 196 XX.18 [01089] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.60 (bs, 1H), 8.37 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 4.9 Hz, 1H), 7.81 (dd, J.sub.1 = 1.9 Hz, J.sub.2 = 7.8 Hz, 1H), 7.35 (d, J = 3.4 Hz, 2H), 6.99-6.87 (m, 7H), 3.40 (s, 3H), 2.08 (s, 3H), 1.76 (s, 6H), 1.69 (s, 6H). LC-MS: m/z 455.3 (M + H).sup.+ 315 197 XV.26 [01090] .sup.1H NMR (400 MHz, DMSO-d6) δ 13.6 (bs, 1H), 12.1 (s, 1H), 8.74 (d, J = 8.3 Hz, 1H), 8.64 (s, 1H), 8.05 (d, J = 7.8 Hz, 1H), 7.81 (d, J = 8.4 Hz, 2H), 7.63 (d, J = 7.3 Hz, 1H), 7.32 (d, J = 8.3 Hz, 2H), 7.17-7.05 (m, 5H), 2.06 (bs, 3H), 1.86 (s, 6H), 1.74 (s, 6H). LC- MS: m/z 467.3 (M + H).sup.+ 316 198 XV.27 [01091] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.90 (bs, 1H), 10.10 (s, 1H), 8.55 (s, 1H), 8.40 (s, 1H), 8.04 (d, J = 7.8 Hz, 1H), 7.88 (d, J = 8.3 Hz, 2H), 7.64 (d, J = 7.9 Hz, 1H), 7.44 (t, J = 7.9 Hz, 1H), 7.31 (d, J = 8.3 Hz, 2H), 7.07 (d, J = 8.3 Hz, 2H), 7.02 (d, J = 5.4 Hz, 2H), 2.06 (s, 3H), 1.86 (s, 6H), 1.73 (s, 6H). LC-MS: m/z 467.3 (M + H).sup.+ 317 199 VI.51 [01092] .sup.1H NMR (400 MHz, DMSO-d6) δ 13.80- 12.40 (s, 1H), 8.65 (s, 1H), 7.99 (d, J = 7.2 Hz, 1H), 7.89 (d, J = 7.2 Hz, 1H), 7.78 (d, J = 8.8 Hz, 2H), 7.48 (t, J = 7.6 Hz, 1H), 7.32 (d, J = 8.4 Hz, 2H), 7.20-7.15 (m, 4H), 3.99 (s, 3H), 2.06 (s, 3H), 1.87 (s, 6H), 1.74 (s, 6H). LC-MS: m/z 478.2 (M + H).sup.+ 318 200 VI.52 [01093] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.95 (s, 1H), 7.67 (d, J = 6.4 Hz, 1H), 7.50-7.46 (m, 1H), 7.27 (d, J = 8.8 Hz, 2H), 7.20-7.17 (m, 2H), 6.80 (d, J = 8.8 Hz, 2H), 6.63 (d, J = 8.8 Hz, 2H), 6.37 (d, J = 8.4 Hz, 2H), 5.03- 5.01 (m, 1H), 4.23-4.19 (m, 2H), 3.64-3.61 (m, 2H), 3.14 (s, 3H), 2.04 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 509.3 (M + H).sup.+ 319 201 XII.41 [01094] .sup.1H NMR (400 MHz, DMSO-d6) δ 13.00 (bs, 1H), 9.04 (s, 1H), 7.78 (m, 1H), 7.62 (d, J = 7.2 Hz, 3H), 7.34 (d, J = 6.4 Hz, 1H), 7.16 (d, J = 8.0 Hz, 2H), 7.00-6.92 (m, 5H), 2.12 (m, 1H), 1.65 (s, 2H), 1.49-1.32 (m, 8H), 1.17 (s, 2H), 0.85 (s, 6H). LC-MS: m/z 468.3 (M + H).sup.+ 320 202 XII.42 [01095] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.99 (bs, 1H), 9.07 (s, 1H), 7.90 (s, 1H), 7.64 (m, 3H), 7.36 (d, J = 6.8 Hz, 2H), 7.11 (t, J = 7.9 Hz, 2H), 7.00 (m, 6H), 6.66 (m, 3H), 3.56 (m, 2H), 1.54 (m, 2H), 1.34 (m, 2H), 0.88 (t, J = 7.3 Hz, 3H). LC-MS: m/z 453.3 (M + H).sup.+ 321 203 XII.43 [01096] .sup.1H NMR (400 MHz, DMSO-d6) δ 10.4 (bs, 1H), 7.59 (m, 1H), 7.47 (m, 3H), 7.32 (d, J = 2.4 Hz, 2H), 6.96 (m, 4H), 2.05 (bs, 3H), 1.86 (s, 6H), 1.76 (s, 6H). LC-MS: m/z 475.2 (M + H).sup.+ 322 204 XII.44 [01097] .sup.1H NMR (400 MHz, DMSO-d6) δ 13.50- 12.50 (bs, 2H), 8.72 (d, J = 2.0 Hz, 2H), 8.11 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 8.4 Hz, 2H), 7.35 (d, J = 8.0 Hz, 2H), 7.14-7.03 (m, 6H), 6.90 (d, J = 9.2 Hz, 2H), 3.27 (s, 3H), 2.05 (s, 3H), 1.86 (s, 6H), 1.73 (s, 6H). LC-MS: m/z 493.4 323 205 VI.53 [01098] .sup.1H NMR (400 MHz, DMSO-d6) δ 13.00- 12.80 (bs, 1H), 9.50-9.40 (bs, 1H), 7.84 (d, J = 7.6 Hz, 1H), 7.8 (s, 1H), 7.3 (t, J = 8.0 Hz, 1H), 7.07- 6.83 (m, 9H), 6.65 (t, J = 7.2 Hz, 1H), 3.47 (s, 2H), 1.98 (s, 3H), 1.73-1.62 (m, 12H). LC-MS: m/z 469.2 (M + H).sup.+ 324 206 XV.28 [01099] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.92 (s, 1H), 9.41 (s, 1H), 7.73- J = 7.6 Hz, 1H), 7.26 (d, J = 8.4 Hz, 2H), 7.17 (d, J = 8.8 Hz, 2H), 7.08 (d, J = 8.8 Hz, 2H), 7.0 (d, J = 8.4 Hz, 1H), 3.33 (s, 3H), 2.01 (s, 3H), 1.79 (s, 6H), 1.69 (s, 6H). LC-MS: m/z 482.3 (M + H).sup.+ 325 207 XX.19 [01100] .sup.1H NMR (400 MHz, DMSO-d6) δ 13.85 (bs, 1H), 11.20 (bs, 1H), 8.46 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 4.8 Hz, 1H), 8.31 (dd, J.sub.1 = 1.6 Hz, J.sub.2 = 7.6 Hz, 1H), 7.94 (d, J = 8.8 Hz, 2H), 7.44 (dd, J = 8.8 Hz, 2H), 7.32 (d, J = 8.4 Hz, 2H), 7.05- 6.98 (m, 3H), 3.09 (s, 3H), 2.04 (s, 3H), 1.84 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 518.3 (M + H).sup.+ 326 208 XX.20 [01101] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.89 (bs, 1H), 7.71 (d, J = 7.6 Hz, 1H), 7.55-7.51 (m, 1H), 7.26 (t, J = 7.6 Hz, 2H), 6.81-6.76 (m, 6H), 6.55 (d, J = 9.2 Hz, 2H), 3.50 (s, 2H), 3.16 (s, 3H), 3.05 (s, 3H), 1.97 (s, 3H), 1.69-1.60 (m, 12H). LC-MS: m/z 497.3 (M + H).sup.+ 327 209 VI.54 [01102] .sup.1H NMR (400 MHz, DMSO-d6) δ 7.62-7.60 (m, 3H), 7.39-7.28 (m, 4H), 7.19 (t, J = 7.2 Hz, 1H), 7.12-7.04 (m, 7H), 6.91 (d, J = 8.0 Hz, 2H), 3.11-3.08 (m, 1H), 1.12 (d, J = 6.8 Hz, 6H). LC-MS: m/z 424.2 (M + H).sup.+ 328 210 VI.55 [01103] .sup.1H NMR (400 MHz, DMSO-d6) δ 14.00-13.20 (bs, 1H), 8.50 (s, 1H), 8.02 (d, J = 8.4 Hz, 1H), 7.92 (d, J = 7.2 Hz, 1H), 7.59 (t, J = 8.0 Hz, 1H), 7.51-7.47 (m, 2H), 7.31-7.27 (m, 4H), 7.16 (d, J = 8.4 Hz, 2H), 3.96 (s, 3H), 2.04 (s, 3H), 1.84 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 478.2 (M + H).sup.+ 329 211 XV.29 [01104] .sup.1H NMR (400 MHz, DMSO- d6) δ 10.80-10.20 (bs, 1H), 10.16 (s, 1H), 7.98-7.94 (m, 3H), 7.84 (d, J = 8.4 Hz, 2H), 7.44-7.35 (m, 3H), 7.33-7.24 (m, 3H), 7.21-7.20 (m, 3H), 7.13 (d, J = 7.2 Hz, 1H), 6.90-6.86 (m, 1H), 3.07-3.01 (m, 1H), 1.13 (d, J = 7.2 Hz, 6H). LC-MS: m/z 451.2 (M + H).sup.+ 330 212 XV.30 [01105] .sup.1H NMR (400 MHz, DMSO-d6) δ 13.21 (s, 1H), 10.19 (s, 1H), 8.07 (t, J = 7.8 Hz, 1H), 8.02 (d, J = 8.3 Hz, 2H), 7.85 (d, J = 7.4 Hz, 1H), 7.70 (d, J = 8.3 Hz, 2H), 7.33 (m, 5H), 2.06 (s, 3H), 1.87 (s, 6H), 1.74 (s, 6H). LC-MS: m/z 469.2 (M + H).sup.+ 331 213 [01106] LC-MS: m/z 481.2 (M + H).sup.+ 333 214 XV.31 [01107] .sup.1H NMR (400 MHz, DMSO-d6) δ 13.17- 13.16 (bs, 1H), 10.17 (s, 1H), 9.77 (s, 1H), 6.93 (dd, J.sub.1 = 1.6 Hz, J.sub.2 = 8.0 Hz, 1H), 7.79 (s, 1H), 7.69 (d, J = 8.8 Hz, 2H), 7.63-7.62 (m, 1H), 7.49- 7.42 (m, 3H), 7.33-7.29 (m, 3H), 6.85-6.81 (m, 1H), 2.06 (s, 3H), 1.83 (s, 6H), 1.70 (s, 6H). LC-MS: m/z 467.3 (M + H).sup.+ 334 215 XV.32 [01108] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.95 (s, 1H), 10.06 (s, 1H), 7.94 (d, J = 8.3 Hz, 2H), 7.90 (d, J = 7.3 Hz, 1H), 7.68- 7.63 (m, 3H), 7.37 (t, J = 6.8 Hz, 1H), 7.32 (d, J = 8.8 Hz, 2H), 7.16 (d, J = 8.3 Hz, 1H), 6.96 (d, J = 8.3 Hz, 2H), 2.06 (s, 3H), 1.86 (s, 6H), 1.74 (s, 6H). LC-MS: m/z 468.1 (M + H).sup.+ 335 216 XV.33 [01109] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.65 (bs, 1H), 9.91 (s, 1H), 7.93- 7.87 (m, 3H), 7.68 (d, J = 8.8 Hz, 2H), 7.34 (d, J = 8.0 Hz, 1H), 7.29 (d, J = 8.8 Hz, 2H), 7.22-7.16 (m, 3H), 6.74 (t, J = 7.6 Hz, 1H), 2.14-2.13 (m, 1H), 1.69 (s, 2H), 1.53- 1.33 (m, 8H), 0.86 (s, 6H). LC-MS: m/z 495.3 (M + H).sup.+ 336 217 [01110] LC-MS: m/z 468.2 (M + H).sup.+ 337 218 VI.56 [01111] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.8 (bs, 1H), 7.70 (d, J = 7.6 Hz, 1H), 7.53 (t, J = 8.0 Hz, 1H), 7.26-7.19 (m, 4H), 6.92 (d, J = 8.8 Hz, 2H), 6.85 (d, J = 8.8 Hz, 2H), 6.59 (d, J = 7.2 Hz, 2H), 3.20-3.19 (m, 4H), 3.16 (s, 3H), 3.12-3.11 (m, 4H), 2.04 (s, 3H), 1.82 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 522.3 (M + H).sup.+ 338 219 XII.45 [01112] .sup.1H NMR (400 MHz, DMSO-d6) δ 13.00 (bs, 1H), 9.16 (s, 1H), 8.26 (s, 1H), 7.73 (d, J = 8.4 Hz, 2H), 7.68-7.63 (m, 3H), 7.37 (d, J = 6.8 Hz, 1H), 7.18 (s, 1H), 7.08 (d, J = 8.8 Hz, 2H), 6.98 (d, J = 8.4 Hz, 1H), 6.91 (d, J = 8.4 Hz, 2H), 2.05 (s, 9H), 1.65 (s, 6H). LC-MS: m/483.1z (M + H).sup.+ 339 220 XII.46 [01113] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.0 (s, 1H), 9.81 (s, 1H), 7.86 (d, J = 7.6 Hz, 1H), 7.49 (d, J = 8.4 Hz, 2H), 7.25 (d, J = 8.8 Hz, 2H), 7.13- 7.01 (m, 6H), 6.58 (t, J = 6.8 Hz, 1H), 2.83 (t, J = 7.6 Hz, 2H), 2.56 (t, J = 8.0 Hz, 2H), 2.04 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 495.3 (M + H).sup.+ 340 221 VI.57 [01114] .sup.1H NMR (400 MHz, DMSO-d6) δ 13.0 (bs, 1H), 8.20 (bs, 1H), 7.70- 7.60 (m, 1H), 7.60-7.50 (m, 1H), 7.35-7.31 (m, 2H), 7.23 (d, J = 8.4 Hz, 2H), 7.10-6.97 (m, 4H), 6.71 (bs, 2H), 3.26 (s, 3H), 2.04 (s, 3H), 1.82 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 481.2 (M + H).sup.+ 341 222 XV.35 [01115] .sup.1H NMR (400 MHz, DMSO-d6) δ 13.10 (bs, 1H), 10.14 (s, 1H), 9.88 (bs, 1H), 7.93 (d, J = 7.6 Hz, 1H), 7.79 (s, 1H), 7.68 (d, J = 8.8 Hz, 2H), 7.61 (d, J = 7.6 Hz, 1H), 7.50-7.40 (m, 3H), 7.32- 7.29 (m, 3H), 6.82 (t, J = 7.6 Hz, 1H), 2.14-2.10 (m, 1H), 1.68 (s, 2H), 1.53-1.43 (m, 8H), 1.18 (s, 2H), 0.86 (s, 6H). LC-MS: m/z 495.3 (M + H).sup.+ 342 223 XVIII.3 [01116] .sup.1H NMR (400 MHz, DMSO-d6) δ 13.8 (bs, 1H), 11.0 (bs, 1H), 8.84 (s, 1H), 7.90 (d, J = 7.2 Hz, 1H), 7.59 (d, J = 8.8 Hz, 2H), 7.55-7.48 (m, 2H), 7.43 (s, 1H), 7.33- 7.28 (m, 2H), 7.09 (t, J = 8.0 Hz, 1H), 6.82 (d, J = 8.8 Hz, 2H), 2.05 (s, 3H), 1.85 (s, 6H), 1.73 (s, 6H). LC-MS: m/z 535 (M + H).sup.− 343 224 XV.36 [01117] .sup.1H NMR (400 MHz, DMSO-d6) δ 10.32 (s, 1H), 7.94 (d, J = 7.6 Hz, 1H), 7.84-7.80 (m, 3H), 7.62 (d, J = 7.6 Hz, 1H), 7.52-7.46 (m, 4H), 7.43- 7.31 (m, 2H), 7.27-7.19 (m, 3H), 7.13 (d, J = 8.0 Hz, 1H), 6.82 (t, J = 7.6 Hz, 1H), 3.05-3.01 (m, 1H), 1.13 (d, J = 6.8 Hz, 6H). LC-MS: m/z 451.2 (M + H).sup.+ 344 225 XV.37 [01118] .sup.1H NMR (400 MHz, DMSO-d6) δ 14.00-13.8 (bs, 1H), 12.30 (s, 1H), 10.35 (s, 1H), 8.71 (d, J = 8.0 Hz, 1H), 8.14-8.07 (m, 5H), 7.27-7.67 (m, 3H), 7.35 (d, J = 8.0 Hz, 2H), 7.24 (t, J = 8.0 Hz, 1H), 2.06 (s, 3H), 1.87 (s, 6H), 1.74 (s, 6H). LC- MS: m/z 495.1 (M + H).sup.+ 345 226 XII.47 [01119] .sup.1H NMR (400 MHz, DMSO-d6) δ 13.42 (s, 1H), 7.81 (d, J = 6.9 Hz, 1H), 7.61 (t, J = 7.3 Hz, 1H), 7.41 (t, J = 7.8 Hz, 1H), 7.28 (d, J = 7.9 Hz, 1H), 7.14 (d, J = 8.8 Hz, 2H), 6.86 (d, J = 8.8 Hz, 2H), 6.70 (d, J = 8.3 Hz, 2H), 6.59 (d, J = 8.8 Hz, 2H), 4.25-4.19 (m, 1H), 3.13 (s, 3H), 2.03 (s, 3H), 1.80 (s, 6H), 1.71 (s, 6H), 1.00 (d, J = 6.3 Hz, 6H). LC-MS: m/z 495.3 (M + H).sup.+ 346 227 XV.38 [01120] .sup.1H NMR (400 MHz, DMSO-d6) δ 13.10 (bs, 1H), 9.94 (s, 1H), 9.69 (s, 1H), 8.01 (d, J = 8.8 Hz, 2H), 7.94 (d, J = 8.8 Hz, 2H), 7.78 (t, J = 7.6 Hz, 1H), 7.70 (d, J = 8.8 Hz, 2H), 7.51 (d, J = 7.2 Hz, 1H), 7.30 (d, J = 8.4 Hz, 2H), 7.10 (d, J = 8.0 Hz, 1H), 2.15-2.13 (m, 1H), 1.69 (s, 2H), 1.53-1.33 (m, 8H), 1.19 (s, 2H), 0.86 (s, 6H). LC-MS: m/z 496.2 (M + H).sup.+ 349 228 VI.58 [01121] .sup.1H NMR (400 MHz, DMSO-d6) δ 15.33 (s, 1H), 8.63 (d, J = 8.3 Hz, 1H), 8.04 (s, 1H), 7.99 (d, J = 7.3 Hz, 1H), 7.87 (d, J = 8.3 Hz, 2H), 7.58 (s, 1H), 7.36 (s, 2H), 7.27 (t, J = 7.3 Hz, 1H), 6.96- 6.90 (m, 4H), 2.06 (s, 3H), 1.87 (s, 6H), 1.74 (s, 6H). LC-MS: m/z 545.1 (M + H).sup.− 350 229 VI.59 [01122] .sup.1H NMR (400 MHz, DMSO-d6) δ 13.6 (bs, 1H), 12.02 (s, 1H), 8.73 (d, J = 8.3 Hz, 1H), 8.30 (s, 1H), 8.04 (d, J = 6.8 Hz, 1H), 7.79 (d, J = 8.4 Hz, 2H), 7.64 (d, J = 7.3 Hz, 1H), 7.44 (D, J = 1.5 Hz, 1H), 7.39-7.32 (m, 2H), 7.16 (t, J = 7.8 Hz, 1H), 6.99 (d, J = 8.3 Hz, 2H), 2.07 (s, 3H), 1.87 (s, 6H), 1.74 (s, 6H). LC-MS: m/z 501.1 (M + H).sup.+ 353 230 XV.39 [01123] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.8 (bs, 1H), 10.02 (s, 1H), 7.80 (d, J = 7.6 Hz, 1H), 7.66- 7.61 (m, 3H), 7.41-7.29 (m, 4H), 7.32-7.21 (m, 2H), 7.09 (s, 1H), 6.62 (d, J = 7.2 Hz, 1H), 3.25 (s, 3H), 2.05 (s, 3H), 1.85 (s, 6H), 1.73 (s, 6H). LC- MS: m/z 481.2 (M + H).sup.+ 355 231 XX.21 [01124] .sup.1H NMR (400 MHz, DMSO-d6) δ 13.01 (bs, 1H), 8.57 (d, J = 3.2 Hz, 1H), 8.13-8.11 (m, 1H), 7.34-7.26 (m, 5H), 7.03 (d, J = 8.4 Hz, 2H), 6.80 (d, J = 8.8 Hz, 2H), 3.38 (s, 3H), 3.03 (s, 3H), 2.04 (s, 3H), 1.84 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 532.2 (M + H).sup.+ 356 232 [01125] LC-MS: m/z 493.4 (M − H).sup.+ 357 233 XX.22 [01126] .sup.1H NMR (400 MHz, DMSO-d6) δ 7.42-7.38 (m, 2H), 7.17-7.15 (m, 1H), 7.11 (t, J = 7.6 Hz, 2H), 7.03-7.01 (m, 3H), 6.87 (d, J = 8.8 Hz, 2H), 6.71-6.69 (m, 1H), 6.51 (d, J = 9.2 Hz, 2H), 3.16 (s, 3H), 3.15 (s, 3H), 2.04 (s, 9H), 1.64 (s, 6H). LC- MS: m/z 510.3 (M + H).sup.+ 358 234 XII.49 [01127] .sup.1H NMR (400 MHz, DMSO-d6) δ 13.68 (s, 1H), 10.58 (s, 1H), 10.19 (s, 1H), 8.43 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 4.8 Hz, 1H), 8.28 (dd, J.sub.1 = 1.7 Hz, J.sub.2 = 7.6 Hz, 1H), 8.14 (s, 1H), 8.06 (d, J = 8.0 Hz, 1H), 7.7 (d, J = 8.4 Hz, 2H), 7.59 (d, J = 7.6 Hz, 1H), 7.47 (t, J = 7.6 Hz, 1H), 7.33 (d, J = 4.8 Hz, 2H), 6.92 (dd, J.sub.1 = 4.8 Hz, J.sub.2 = 7.6 Hz, 1H), 2.06 (s, 3H), 1.86 (s, 6H), 1.74 (s, 6H). LC-MS: m/z 468.1 (M + H).sup.+ 359 235 XII.50 [01128] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.85 (s, 1H), 10.12 (s, 1H), 8.57 (s, 1H), 7.68-7.61 (m, 4H), 7.45-7.27 (m, 8H), 2.05 (s, 3H), 1.86 (s, 6H), 1.73 (s, 6H). LC-MS: m/z 465.1 (M − H).sup.− 360 236 XX.23 [01129] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.99 (bs, 1H), 7.78 (d, J = 7.9 Hz, 1H), 7.60 (d, J = 7.8 Hz, 1H), 7.43 (d, J = 8.8 Hz, 2H), 7.37-7.31 (m, 3H), 7.23-7.12 (m, 3H), 6.94 (d, J = 8.8 Hz, 2H), 6.87 (d, J = 8.3 Hz, 1H), 6.61 (d, J = 8.8 Hz, 2H), 3.17 (s, 3H), 2.97-2.91 (m, 1H), 1.09 (d, J = 7.3 Hz, 6H), LC-MS: m/z 472.2 (M + H).sup.+ 361 237 VI.60 [01130] .sup.1H NMR (400 MHz, DMSO-d6) δ 13.75 (s, 1H), 12.15 (s, 1H), 8.69 (d, J = 8.3 Hz, 1H), 8.05 (d, J = 8.3 Hz, 1H), 7.96 (d, J = 8.8 Hz, 2H), 7.65 (t, J = 7.3 Hz, 1H), 7.43 (d, J = 8.8 Hz, 2H), 7.20 (t, J = 7.8 Hz, 1H), 7.12 (d, J = 8.8 Hz, 2H), 7.07 (d, J = 8.3 Hz, 2H), 2.07 (s, 3H), 1.88 (s, 6H), 1.74 (s, 6H). LC-MS: m/z 468.1 (M + H).sup.+ 362 238 XX.24 [01131] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.76 (s, 1H), 7.41 (t, J = 8.3 Hz, 1H), 7.12 (d, J = 8.8 Hz, 2H), 7.00 (d, J = 8.3 Hz, 1H), 6.91 (d, J = 8.4 Hz, 2H), 6.76 (d, J = 7.8 Hz, 1H), 6.66 (d, J = 8.3 Hz, 2H), 6.60 (d, J = 8.8 Hz, 2H), 3.82 (s, 3H), 3.13 (s, 3H), 3.09 (s, 3H), 2.02 (s, 3H), 1.80 (s, 6H), 1.71 (s, 6H). LC-MS: m/z 497.3 (M + H).sup.+ 363 239 XV.40 [01132] .sup.1H NMR (400 MHz, DMSO-d6) δ 8.66 (d, J = 8.4 Hz, 1H), 8.29 (s, 1H), 8.02 (dd, J.sub.1 = 1.2 Hz, J.sub.2 = 7.6 Hz, 2H), 7.65 (s, 1H), 7.44-7.32 (m, 3H), 7.26 (d, J = 8.4 Hz, 2H), 7.20 (d, J = 7.6 Hz, 1H), 7.10-7.04 (m, 2H), 2.05 (s, 3H), 1.85 (s, 6H), 1.73 (s, 6H). LC-MS: m/z 467.3 (M + H).sup.+ 364 240 XV.41 [01133] .sup.1H NMR (400 MHz, DMSO-d6) δ 10.4 (s, 1H), 8.4 (s, 1H), 8.26 (s, 1H), 8.00 (d, J = 9.2 Hz, 1H), 7.66 (d, J = 7.6 Hz, 1H), 7.59 (s, 1H), 7.45 (t, J = 7.6 Hz, 1H), 7.35-7.32 (m, 2H), 7.26 (d, J = 8.8 Hz, 2H), 7.21-7.19 (m, 1H), 7.08 (d, J = 8.8 Hz, 2H), 2.05 (s, 3H), 1.84 (s, 6H), 1.73 (s, 6H). LC-MS: m/z 467.3 (M + H).sup.+ 366 241 XII.53 [01134] .sup.1H NMR (400 MHz, DMSO-d6) δ 13.69 (bs, 1H), 10.61 (s, 1H), 9.99 (s, 1H), 8.42 (dd, J.sub.1 = 1.0 Hz, J.sub.2 = 4.8 Hz, 1H), 8.28 (dd, J.sub.1 = 1.0 Hz, J.sub.2 = 7.6 Hz, 1H), 8.20 (s, 1H), 8.09 (d, J = 8.0 Hz, 1H), 7.67 (m, 1H), 7.54-7.46 (m, 3H), 7.39-7.38 (m, 1H), 6.92 (dd, J.sub.1 = 4.8 Hz, J.sub.2 = 7.6 Hz, 1H), 2.07 (s, 3H), 1.88 (d, J = 2.4 Hz, 6H), 1.71 (s, 6H). LC-MS: 502.2 (M + H).sup.+ 367 242 XII.54 [01135] .sup.1H NMR (400 MHz, DMSO-d6) δ 10.0 (s, 1H), 9.81-9.79 (bs, 1H), 7.93 (dd, J.sub.1 = 1.2 Hz, J.sub.2 = 7.6 Hz, 1H), 7.82 (s, 1H), 7.65-7.63 (m, 1H), 7.51-7.43 (m, 5H), 7.38- 7.36 (m, 1H), 7.32 (d, J = 8.0 Hz, 1H), 6.86-6.82 (m, 1H), 2.07 (s, 3H), 1.86 (d, J = 2.4 Hz, 6H), 1.74 (s, 6H). LC-MS: m/z 501.1 (M + H).sup.+ 369 243 [01136] LC-MS: m/z 493.4 (M − H).sup.+ 370 244 Com- pound 14 [01137] .sup.1H NMR (400 MHz, DMSO-d6) δ 8.24 (s, 1H), 7.63 (d, J = 8.0 Hz, 1H), 7.45 (d, J = 8.8 Hz, 1H), 7.53 (d, J = 3.2 Hz, 1H), 7.39 (d, J = 8.8 Hz, 2H), 7.26 (d, J = 8.8 Hz, 2H), 7.19-7.14 (m, 3H), 7.11-7.07 (m, 3H), 6.63 (d, J = 2.4 Hz, 1H), 2.06 (s, 3H), 1.85 (d, J = 2.4 Hz, 6H), 1.73 (s, 6H). LC-MS: m/z 491.3 (M + H).sup.+ 371 245 Com- pound 14 [01138] .sup.1H NMR (400 MHz, DMSO-d6) δ 7.70-7.58 (m, 4H), 7.21-7.14 (m, 3H), 7.07 (d, J = 8.0 Hz, 1H), 6.96 (d, J = 8.8 Hz, 2H), 6.89-6.84 (m, 5H), 6.35 (d, J = 15.6 Hz, 1H), 2.04 (s, 3H), 1.86 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 465.3 (M + H).sup.+ 372 246 XVIII.4 [01139] .sup.1H NMR (400 MHz, DMSO-d6) δ 13.21 (bs, 1H), 10.11 (s, 1H), 9.71 (bs, 1H), 7.92 (dd, J.sub.1 = 1.6 Hz, J.sub.2 = 8.0 Hz, 1H), 7.53 (s, 1H), 7.49-7.35 (m, 4H), 7.23 (d, J = 8.4 Hz, 2H), 7.07-7.01 (m, 3H), 6.90 (t, J = 7.6 Hz, 1H), 2.00 (s, 3H), 1.76 (s, 6H), 1.68 (s, 6H). LC-MS: m/z 503.2 (M + H).sup.+ 373 247 XII.55 [01140] .sup.1H NMR (400 MHz, DMSO-d6) δ 11.89 (s, 1H), 10.22 (s, 1H), 9.22 (s, 1H), 8.36-8.28 (m, 2H), 7.7-7.51 (m, 4H), 7.33 (d, J = 8.0 Hz, 2H), 6.93 (s, 1H), 2.06 (s, 3H), 1.86 (s, 6H), 1.73 (s, 6H). LC-MS: m/z 502.2 (M + H).sup.+ 376 248 XII.57 [01141] .sup.1H NMR (400 MHz, DMSO-d6) δ 13.00-12.8 (bs, 1H), 10.07 (s, 1H), 8.03 (bs, 1H), 7.66 (d, J = 8.4 Hz, 2H), 7.56 (s, 1H), 7.41 (d, J = 8.0 Hz, 1H), 7.36-7.26 (m, 4H), 7.21 (dd, J.sub.1 = 0.8 Hz, J.sub.2 = 7.6 Hz, 1H), 6.86 (d, J = 8.0 Hz, 1H), 6.68 (d, J = 8.4 Hz, 1H), 3.79 (s, 3H), 2.06 (s, 3H), 1.85 (d, J = 2.4 Hz, 6H), 1.73 (s, 6H). LC-MS: m/z 497.3 (M + H).sup.+ 377 249 XII.58 [01142] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.16 (s, 1H), 9.12 (s, 1H), 7.99 (s, 1H), 7.21 (d, J = 8.4 Hz, 2H), 7.08-6.98 (m, 6H), 6.07 (d, J = 2.4 Hz, 1H), 6.0 (d, J = 2.4 Hz, 1H), 3.81 (s, 3H), 3.67 (s, 3H), 2.04 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 499.2 (M + H).sup.+ 379 250 XII.59 [01143] .sup.1H NMR (400 MHz, DMSO-d6) δ 13.2 (bs, 1H), 9.2 (bs, 1H), 7.39 (d, J = 2.9 Hz, 1H), 7.22 (d, J = 8.8 Hz, 2H), 7.11 (d, J = 6.3 Hz, 1H), 7.09 (d, J = 5.8 Hz, 2H), 7.03 (dd, J.sub.1 = 2.4 Hz, J.sub.2 = 8.8 Hz, 1H), 6.97 (d, J = 8.8 Hz, 2H), 6.88 (d, J = 8.8 Hz, 2H), 3.71 (s, 3H), 3.21 (s, 3H), 2.04 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 483.3 (M + H).sup.+ 380 251 XII.60 [01144] .sup.1H NMR (400 MHz, DMSO-d6) δ 9.57 (s, 1H), 8.04 (s, 1H), 7.80 (d, J = 8.8 Hz, 1H), 7.22 (d, J = 8.4 Hz, 2H), 7.12 (d, J = 8.8 Hz, 2H), 7.06 (d, J = 8.8 Hz, 2H), 7.01 (d, J = 8.8 Hz, 2H), 6.41 (d, J = 2.0 Hz, 1H), 6.28 (dd, J.sub.1 = 2.4 Hz, J.sub.2 = 8.8 Hz, 2H), 3.69 (s, 3H), 2.06 (s, 3H), 1.83 (d, J = 2.0 Hz, 2H), 1.69 (s, 6H). LC-MS: m/z 469.3 (M + H).sup.+ 381 252 XII.61 [01145] .sup.1H NMR (400 MHz, DMSO-d6) δ 13.62 (bs, 1H), 10.36 (s, 1H), 8.36 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 4.8 Hz, 1H), 8.24 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 8.0 Hz, 1H), 7.71- 7.67 (m, 2H), 7.49 (d, J = 2.0 Hz, 1H), 7.35 (dd, J.sub.1 = 2.4 Hz, J.sub.2 = 8.8 Hz, JH), 6.98-6.93 (m, 3H), 6.85 (dd, J.sub.1 = 4.8 Hz, H.sub.2 = 7.6 Hz, 1H), 2.06 (s, 3H), 1.86 (s, 6H), 1.76 (s, 6H). LC-MS: m/z 475.2 (M + H).sup.+ 383 253 XII.62 [01146] .sup.1H NMR (400 MHz, DMSO-d6) δ 13.15 (bs, 1H), 9.65 (bs, 1H), 7.88 (dd, J.sub.1 = 1.6 Hz, J.sub.2 = 8.0 Hz, 1H), 7.49 (d, J = 2.4 Hz, 1H), 7.37-7.33 (m, 2H), 7.32 (d, J = 2.0 Hz, 2H), 7.09 (d, J = 8.4 Hz, 1H), 7.03 (d, J = 8.8 Hz, 1H), 6.94 (d, J = 8.8 Hz, 2H), 6.74 (t, J = 7.6 Hz, 1H), 2.14 (m, 1H), 1.69 (s, 2H), 1.53-1.32 (m, 8H), 1.18 (s, 2H), 0.86 (s, 6H). LC-MS: m/z 502.2 (M + H).sup.+ 384 254 XII.63 [01147] .sup.1H NMR (400 MHz, DMSO-d6) δ 11.20 (bs, 1H), 8.27-8.26 (m, 1H), 8.20 (dd, J.sub.1 = 2.4 Hz, J.sub.2 = 7.6 Hz, 1H), 7.72- 7.68 (m, 2H), 7.47 (d, J = 2.4 Hz, 1H), 7.30 (dd, J.sub.1 = 2.4 Hz, J.sub.2 = 8.8 Hz, 1H), 6.94-6.92 (m, 3H), 6.80-6.77 (m, 1H), 2.14- 2.13 (m, 1H), 1.68 (s, 2H), 1.52-1.23 (m, 8H), 1.18 (s, 2H), 0.85 (s, 6H). LC-MS: m/z 503.3 (M + H).sup.+ 385 255 VI.61 [01148] .sup.1H NMR (400 MHz, DMSO-d6) δ 13.49 (s, 1H), 10.29 (s, 1H), 8.33 (s, 1H), 8.21 (d, J = 6.4 Hz, 1H), 8.08-8.05 (bs, 1H), 7.60-7.52 (bs, 2H), 7.22-6.46 (m, 12H), 3.60- 3.58 (bs, 2H), 1.60-1.54 (bs, 2H), 1.33 (bs, 2H), 0.85 (t, J = 6.8 Hz, 3H). LC-MS: m/z 453.3 (M + H).sup.+ 386 256 XV.44 [01149] .sup.1H NMR (400 MHz, DMSO-d6) δ 13.5 (bs, 1H), 10.42 (bs, 1H), 8.31-8.26 (m, 2H), 8.18 (d, J = 7.6 Hz, 1H), 7.57 (d, J = 8.4 Hz, 2H), 7.16- 7.06 (m, 4H), 6.94 (d, J = 8.4 Hz, 2H), 6.77 (dd, J.sub.1 = 4.8 Hz, J.sub.2 = 7.6 Hz, 1H), 3.27 (m, 6H), 1.84- 1.45 (m, 4H), 1.30-1.1 (m, 4H), 0.90-0.70 (m, 6H). LC-MS: m/z 461.3 (M + H).sup.+ 387 257 XV.45 [01150] .sup.1H NMR (400 MHz, DMSO-d6) δ 10.34 (s, 1H), 8.50-8.40 (bs, 1H), 8.34-8.25 (m, 2H), 7.66 (d, J = 8.4 Hz, 2H), 7.60 (d, J = 8.4 Hz, 2H), 7.25 (s, 1H), 7.13 (d, J = 8.8 Hz, 2H), 6.97 (d, J = 8.8 Hz, 2H), 6.84 (dd, J.sub.1 = 4.8 Hz, J.sub.2 = 7.6 Hz, 1H), 2.06 (s, 9H), 1.65 (s, 6H). LC- MS: m/z 483.1 (M + H).sup.+ 388 258 VI.63 [01151] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.9 (s, 1H), 9.46 (s, 1H), 7.85 (dd, J.sub.1 = 1.6 Hz, J.sub.2 = 8.4 Hz, 1H), 7.52 (s, 1H), 7.34-7.30 (m, 1H), 7.26- 7.18 (m, 3H), 7.11 (d, J = 8.8 Hz, 2H), 7.04 (d, J = 2.4 Hz, 1H), 7.00-6.97 (m, 3H), 6.91-6.84 (m, 4H), 6.67 (t, J = 8.0 Hz, 1H), 3.62 (t, J = 7.2 Hz, 2H), 1.58-1.50 (m, 2H), 1.38-1.29 (m, 2H), 0.88 (t, J = 7.6 Hz, 3H). LC-MS: m/z 486.2 (M + H).sup.+ 389 259 VI.64 [01152] .sup.1H NMR (400 MHz, DMSO-d6) δ 13.24 (s, 1H), 10.2 (s, 1H), 8.32 (s, 1H), 8.22 (d, J = 7.6 Hz, 1H), 7.53 (bs, 2H), 7.22- 6.84 (m, 12H), 3.51 (bs, 2H), 1.54 (s, 2H), 1.34- 1.23 (m, 2H), 0.88 (t, J = 6.8 Hz, 3H). LC-MS: m/z 487.2 (M + H).sup.+ 392 260 XVIII.5 [01153] .sup.1H NMR (400 MHz, DMSO-d6) δ 13.40- 13.20 (bs, 1H), 9.79 (s, 1H), 9.70 (s, 1H), 7.95 (dd, J.sub.1 = 1.2 Hz, J.sub.2 = 8.0 Hz, 1H), 7.62 (d, J = 8.8 Hz, 2H), 7.52-7.43 (m, 2H), 7.32-7.25 (m, 4H), 7.25-7.20 (m, 1H), 6.99-6.95 (m, 1H), 2.02 (s, 3H), 1.79 (d, J = 2.4 Hz, 6H), 1.67 (s, 6H). LC-MS: m/z 537.2 (M + H).sup.+ 393 261 XVIII.6 [01154] .sup.1H NMR (400 MHz, DMSO-d6) δ 13.8 (bs, 1H), 10.85 (s, 1H), 9.71 (s, 1H), 8.46 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 4.8 Hz, 1H), 8.31 (dd, J.sub.1 = 1.6 Hz, J.sub.2 = 7.6 Hz, 1H), 7.92 (d, J = 8.8 Hz, 2H), 7.66 (d, J = 8.8 Hz, 2H), 7.30 (d, J = 2.0 Hz, 1H), 7.26 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 8.4 Hz, 1H), 7.17 (d, J = 8.0 Hz, 1H), 6.99 (dd, J.sub.1 = 5.2 Hz, J.sub.2 = 8.0 Hz, 1H), 2.02 (s, 3H), 1.79 (s, 6H), 1.66 (s, 6H). LC-MS: m/z 538.0 (M + H).sup.+ 394 262 XV.46 [01155] .sup.1H NMR (400 MHz, DMSO-d6) δ 13.70 (bs, 1H), 10.80 (bs, 1H), 9.94 (s, 1H), 8.40 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 4.8 Hz, 1H), 8.27 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 7.6 Hz, 1H), 8.20 (s, 1H), 8.07 (d, J = 7.6 Hz, 1H), 7.60 (d, J = 8.0 Hz, 1H), 7.53 (d, J = 8.4 Hz, 1H), 7.49-7.46 (m, 2H), 7.37 (dd, J.sub.1 = 2.0, J.sub.2 = 8.4 Hz, 1H), 6.90 (dd, J.sub.1 = 4.4 Hz, J.sub.2 = 7.2 Hz, 1H), 2.16- 2.15 (m, 1H), 1.71 (s, 2H), 1.56-1.34 (m, 8H), 1.20 (s, 2H), 0.87 (s, 6H). LC-MS: m/z 503.2 (M + H).sup.+ 395 263 XII.64 [01156] .sup.1H NMR (400 MHz, DMSO-d6) δ 11.40-11.0 (bs, 1H), 10.17 (s, 1H), 7.92 (d, J = 7.2 Hz, 1H), 7.73-7.69 (m, 3H), 7.51 (d, J = 7.2 Hz, 1H), 7.45- 7.38 (m, 2H), 7.29 (d, J = 2.4 Hz, 2H), 7.22-7.18 (m, 2H), 7.03 (d, J = 8.8 Hz, 2H), 6.86-6.74 (m, 4H), 3.65 (t, J = 7.2 Hz, 2H), 1.56-1.53 (m, 2H), 1.36-1.3 (m, 2H), 0.88 (t, J = 7.6 Hz, 3H). LC-MS: m/z 480.3 (M + H).sup.+ 396 264 XVIII.7 [01157] .sup.1H NMR (400 MHz, DMSO-d6) δ 13.31 (s, 1H), 9.80 (s, 1H), 9.73 (s, 1H), 7.94 (dd, J.sub.1 = 1.6 Hz, J.sub.2 = 8.0 Hz, 1H), 7.60 (d, J = 8.8 Hz, 2H), 7.52-7.43 (m, 2H), 7.32-7.24 (m, 4H), 7.16 (d, J = 8.4 Hz, 1H), 6.97 (t, J = 7.6 Hz, 1H), 2.11-2.09 (m, 1H), 1.62 (s, 2H), 1.42-1.32 (m, 8H), 1.15 (s, 2H), 0.83 (s, 6H), LC-MS: m/z 565.2 (M + H).sup.+ 397 265 XVIII.8 [01158] .sup.1H NMR (400 MHz, DMSO-d6) δ 13.80 (bs, 1H), 10.80 (s, 1H), 9.69 (s, 1H), 8.46 (dd, J.sub.1 = 1.6 Hz, J.sub.2 = 4.4 Hz, 1H), 8.30 (dd, J.sub.1 = 1.6 Hz, J.sub.2 = 7.6 Hz, 1H), 7.92 (d, J = 9.2 Hz, 2H), 7.65 (d, J = 8.8 Hz, 2H), 7.29 (d, J = 2.0 Hz, 1H), 7.25 (dd, J.sub.1 = 2.0 Hz, J2 = 8.4 Hz, 1H), 7.16 (d, J = 8.4 Hz, 1H), 6.99 (dd, J.sub.1 = 4.8 Hz, J.sub.2 = 7.6 Hz, 1H), 2.11-2.09 (m, 1H), 1.62 (s, 2H), 1.46- 1.29 (m, 8H), 1.15 (s, 2H), 0.82 (s, 6H). LC- MS: m/z 566.2 (M + H).sup.+ 398 266 XII.65 [01159] .sup.1H NMR (400 MHz, DMSO-d6) δ 13.7 (s, 1H), 10.61 (s, 1H), 10.22 (s, 1H), 8.43 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 4.8 Hz, 1H), 8.28 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 7.6 Hz, 1H), 8.14 (s, 1H), 8.05 (s, 1H), 7.71 (d, J = 8.8 Hz, 2H), 7.52 (s, 1H), 7.47 (s, 1H), 7.23-7.21 (m, 2H), 7.04 (d, J = 8.8 Hz, 2H), 6.92-6.80 (m, 4H), 3.66 (t, J = 7.2 Hz, 2H), 1.57-1.53 (m, 2H), 1.36-1.31 (m, 2H), 0.88 (t, J = 7.6 Hz, 3H). LC-MS: m/z 481.2 (M + H).sup.+ 407 267 XV.47 [01160] .sup.1H NMR (400 MHz, DMSO-d6) δ 13.19 (s, 1H), 9.78 (s, 1H), 8.85 (t, J = 5.8 Hz, 1H), 7.93 (dd, J.sub.1 = 1.5 Hz, J.sub.2 = 8.3 Hz, 1H), 7.87 (d, J = 8.3 Hz, 2H), 7.49-7.40 (m, 2H), 7.32-7.23 (m, 6H), 6.89 (t, J = 6.9 Hz, 1H), 4.43 (d, J = 5.9 Hz, 2H), 2.05 (s, 3H), 1.85 (s, 6H), 1.73 (s, 6H). LC-MS: m/z 481.3 (M + H).sup.+ 408 268 XV.48 [01161] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.00 (bs, 1H), 8.96 (t, J = 5.9 Hz, 1H), 7.91 (d, J = 7.8 Hz, 1H), 7.64 (s, 1H), 7.38- 7.16 (m, 10H), 6.68 (t, J = 7.4 Hz, 1H), 4.41 (d, J = 5.9 Hz, 2H), 2.04 (s, 3H), 1.84 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 481.3 (M + H).sup.+ 420 269 XII.66 [01162] .sup.1H NMR (400 MHz, DMSO- d6) δ 13.2-13.0 (bs, 1H) 9.3- 9.0 (bs, 1H), 7.38 (d, J = 2.8 Hz, 1H), 7.24-7.22 (m, 2H), 7.11-7.05 (m, 4H), 6.98-6.96 (m, 2H), 6.89 (d, J = 9.2 Hz, 2H), 4.04-4.02 (m, 2H), 3.64-3.62 (m, 2H), 3.21 (s, 2H), 2.04 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 572.3 (M + H).sup.+ 453 35 XII.70 [01163] 1H NMR (400 MHz, DMSO-d6): δ 13.10 (s, 1H), 9.12 (s, 1H), 7.37 (d, J = 2.0 Hz, 1H), 7.23 (d, J = 8.4 Hz, 2H), 7.10 (d, J = 9.2 Hz, 2H), 7.05 (dd, J1 = 2.8 Hz, J2 = 9.2 Hz, 2H), 6.97 (d, J = 8.8 Hz, 2H), 6.89 (d, J = 8.8 Hz, 2H), 3.68 (d, J = 6.4 Hz, 2H), 3.21 (s, 3H), 2.04 (s, 3H), 2.01-1.98 (m, 1H), 1.83 (d, J = 2.6 Hz, 6H), 1.72 (s, 6H), 0.97 (d, J = 6.8 Hz, 6H). LC-MS: m/z 525.3 (M + H)+ 473 36 Com- pound 20 [01164] 1H-NMR (400 MHz, DMSO-d6): 12.67 (s, 1H), 10.01 (s, 1H), 9.57 (s, 1H), 7.78 (d, J = 8.8 Hz, 1H), 7.43 (s, 1H), 7.27 (d, J = 8.4 Hz, 2H), 7.15 (d, J = 8.4 Hz, 2H), 7.01-6.95 (m, 5H), 3.57 (t, J = 5.6 Hz, 2H), 3.24 (s, 3H), 3.21 (s, 3H), 2.04 (s, 3H), 1.85 (s, 6H), 1.73 (s, 6H). LC-MS: m/z 554.3 (M + H)+ 521 37 XII.71 [01165] 1H NMR (400 MHz, DMSO-d6): δ 13.20 (bs, 1H), 9.22 (bs, 1H), 7.46 (d, J = 8.8 Hz, 2H), 7.41 (d, J = 2.8 Hz, 1H), 7.29 (d, J = 9.2 Hz, 1H), 7.23- 7.09 (m, 5H), 6.81 (d, J = 8.8 Hz, 2H), 3.74 (s, 3H), 3.27 (s, 3H). LC-MS: m/z 417.2 (M + H)+. 522 38 XII.72 [01166] 1H NMR (400 MHz, DMSO-d6): δ 13.09 (bs, 1H), 9.08 (s, 1H), 7.35 (d, J = 2.8 Hz, 1H), 7.10- 7.02 (m, 6H), 6.94 (d, J = 8.8 Hz, 2H), 6.85 (d, J = 8.8 Hz, 2H), 3.69 (s, 3H), 3.18 (s, 3H), 2.42- 2.39 (m, 1H), 1.76-1.65 (m, 5H), 1.38-1.20 (m, 5H). LC-MS: m/z 431.2 (M + H)+. 525 39 XII.73 [01167] 1H NMR (400 MHz, CDCl3) δ 7.71 (s, 1H), 7.26-7.12 (m, 5H), 6.99 (d, J = 8 Hz, 2H), 6.88- 6.83 (m, 3H), 4.41 (s, 2H), 3.49-3.22 (m, 10H), 2.10-2.07 (m, 7H), 1.89 (s, 5H), 1.79-1.75 (s, 6H). LC-MS: m/z 566.3 (M + H)+. 526 40 XII.74 [01168] 1H NMR (400 MHz, DMSO-d6): δ 7.46 (d, J = 2 Hz, 1H), 7.22 (d, J = 8.4 Hz, 2H), 7.12-7.04 (m, 4H), 6.97 (d, J = 8 Hz, 2H), 6.88 (d, J = 8.4 Hz, 2H), 4.13 (t, J = 5.2 Hz, 2H), 3.2 (s, 3H), 3.06 (s, 2H), 2.55 (s, 6H), 2.04 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 540.3 (M + H)+. 527 41 XII.75 [01169] 1H NMR (400 MHz, DMSO-d6): δ 13.18 (s, 1H), 9.25 (s, 1H), 7.61 (dd, J1 = 2.4 & J2 = 7.6 Hz, 2H), 7.41 (d, J = 3.2 Hz, 1H), 7.30 (d, J = 9.2 Hz, 1H), 7.23-7.16 (m, 4H), 7.09 (dd, J1 = 3.2 Hz, & J2 = 9.2 Hz, 1H), 6.73 (d, J = 9.2 Hz, 2H), 3.74 (s, 3H), 3.27 (s, 3H). LC- MS: m/z 475.1 (M + H)+. 535 42 XII.76 [01170] 1H NMR (400 MHz, DMSO-d6): δ 13.15 (s, 1H), 9.10 (s, 1H), 7.39 (d, J = 3.2 Hz, 1H), 7.23- 7.16 (m, 5H), 7.11-7.07 (m, 3H), 6.81 (dd, J1 = 2.4 Hz, & J2 = 6.8 Hz, 2H), 3.73 (s, 3H), 3.21 (s, 3H). LC-MS: m/z 382.84 (M + H)+ 536 43 XII.77 [01171] 1H NMR (400 MHz, DMSO-d6): δ 7.39 (d, J = 2.8 Hz, 1H), 7.08 (d, J = 8.4 Hz, 5H), 7.03-7.02 (m, 1H), 6.95 (d, J = 8.8 Hz, 2H), 6.85 (d, J = 8.0 Hz, 2H), 4.02 (t, J = 4.0 Hz, 2H), 3.62 (t, J = 4.8 Hz, 2H), 3.30 (s, 3H), 3.19 (s, 3H), 2.46-2.42 (m, 1H), 1.77-1.65 (m, 5H), 1.37-1.23 (m, 5H). LC-MS: m/z 474.3 (M + H)+. 537 44 XII.78 [01172] 1H NMR (400 MHz, DMSO-d6): δ 13.18 (bs, 1H), 8.95 (s, 1H), 7.37- 7.32 (m, 3H), 7.22 (t, J = 9.2 Hz, 1H), 7.08-7.03 (m, 3H), 6.83-6.75 (m, 2H), 6.66 (d, J = 8.4 Hz, 1H), 3.70 (s, 3H), 3.23 (s, 3H), 2.05 (s, 3H), 1.86 (s, 6H), 1.73 (s, 6H). LC-MS: m/z 501.3 (M + H)+. 538 45 XII.79 [01173] 1H NMR (400 MHz, DMSO-d6): δ 11.6-11.2 (bs, 1H), 7.47 (s, 1H), 7.09 (d, J = 8.8 Hz, 1H), 7.04-7.01 (m, 4H), 6.94 (d, J = 8.8 Hz, 2H), 6.81- 6.78 (m, 1H), 6.74 (d, J = 8.4 Hz, 2H), 3.68 (s, 3H), 3.16 (s, 3H), 2.61- 2.59 (m, 1H), 2.29 (s, 1H), 2.19 (s, 1H), 1.66- 1.65 (m, 1H), 1.58-1.51 (m, 3H), 1.44 (d, J = 10 Hz, 1H), 1.31-1.21 (m, 2H), 1.11-1.09 (m, 1H). LC-MS: m/z 443.2 (M + H)+. 541 46 XII.80 [01174] 1H NMR (400 MHz, DMSO-d6): δ 10.48 (s, 1H), 8.39 (dd, J1 = 2.0 Hz & J2 = 4.8 Hz, 1H), 8.27 (dd, J1 = 2 Hz, & J2 = 8.0 Hz, 1H), 7.78 (d, J = 8.8 Hz, 2H), 7.46 (d, J = 8.8 Hz, 2H), 7.21 (d, J = 8.8 Hz, 2H), 6.90-6.87 (m, 1H), 6.82 (d, J = 8.8 Hz, 2H), 3.29 (s, 3H). LC-MS: m/z 388.1 (M + H)+. 542 47 XII.81 [01175] 1H NMR (400 MHz, DMSO-d6): δ 13.10- 12.90 (bs, 1H), 9.02 (s, 1H), 7.23 (d, J = 2.0 Hz, 1H), 7.49 (dd, J1 = 2.0 Hz & J2 = 8.0 Hz, 1H), 7.40 (d, J = 8.8 Hz, 1H), 7.35 (d, J = 2.4 Hz, 2H), 7.05- 6.94 (m, 4H), 6.60 (d, J = 8.8 Hz, 2H), 3.70 (s, 3H), 3.19 (s, 3H). LC-MS: m/z 419.1 (M + H)+. 543 48 XII.82 [01176] 1H NMR (400 MHz, DMSO-d6): δ 13.1 (bs, 1H), 9.63 (s, 1H), 8.03 (d, J = 2 Hz, 1H), 7.92- 7.90 (m, 1H), 7.69 (dd, J1 = 1.6 Hz, & J2 = 8.8 Hz, 1H), 7.40-7.33 (m, 3H), 7.21-7.10 (m, 4H), 6.81- 6.77 (m, 1H). LC-MS: m/z 408 (M + H)+. 544 49 XII.83 [01177] 1H NMR (400 MHz, DMSO-d6): δ 13.22 (bs, 1H), 9.17 (s, 1H), 8.01 (d, J = 2 Hz, 1H), 7.67 (dd, J1 = 1.6 Hz, & J2 = 8.8 Hz, 1H), 7.40 (d, J = 3.2 Hz, 1H), 7.26-7.23 (m, 3H), 7.12-7.07 (m, 4H), 3.73 (s, 3H). LC-MS: m/z 438.0 (M + H)+. 545 50 XII.84 [01178] 1H NMR (400 MHz, DMSO-d6): δ 12.96 (bs, 1H), 8.97 (bs, 1H), 7.33 (d, J = 2.8 Hz, 1H), 7.27 (t, J = 7.8 Hz, 1H), 7.18 (d, J = 8.0 Hz, 1H), 7.12 (d, J = 8.0 Hz, 1H), 7.01- 6.96 (m, 4H), 6.89 (d, J = 8.8 Hz, 1H), 6.33 (d, J = 8.8 Hz, 2H), 3.73 (s, 3H), 3.69 (s, 3H), 3.17 (s, 3H). LC-MS: m/z 379.2 (M + H)+. 546 51 XII.85 [01179] 1H NMR (400 MHz, DMSO-d6): δ 13.03 (s, 1H), 9.54 (s, 1H), 7.88 (d, J = 8 Hz, 1H), 7.42- 7.34 (m, 2H), 7.26-7.20 (m, 3H), 7.09 (d, J = 8.4 Hz, 1H), 7.02 (d, J = 8.4 Hz, 1H), 6.95 (d, J = 8 Hz, 2H), 6.74 (t, J = 7.2 Hz, 1H), 1.80-1.67 (m, 5H), 1.44-1.11 (m, 6H). LC- MS: m/z 422.1 (M + H)+. 547 52 XII.86 [01180] 1H NMR (400 MHz, DMSO-d6): δ 13.0 (s, 1H), 9.1 (s, 1H), 7.35 (d, J = 2.8 Hz, 1H), 7.04-6.91 (m, 8H), 6.79 (d, J = 8.8 Hz, 2H), 3.74-3.70 (m, 7H), 3.17 (s, 3H), 3.06- 3.04 (m, 4H). LC-MS: m/z 434.2 (M + H)+. 548 53 XII.87 [01181] 1H NMR (400 MHz, DMSO-d6): δ 13.2 (s, 1H), 9.2 (s, 1H), 7.39 (d, J = 3.2 Hz, 1H), 7.24-7.09 (m, 8H), 6.84 (d, J = 8.8 Hz, 2H), 3.73 (s, 3H), 3.23 (s, 3H). LC-MS: m/z 433.1 (M + H)+. 549 54 XII.88 [01182] 1H NMR (400 MHz, DMSO-d6): δ 13.15 (bs, 1H), 8.94 (s, 1H), 7.37 (d, J = 2.8 Hz, 1H), 7.24- 7.19 (m, 3H), 7.06-7.03 (m, 3H), 6.82-6.74 (m, 2H), 6.64 (dd, J1 = 2 Hz, & J2 = 8.8 Hz, 1H), 3.70 (s, 3H), 3.23 (s, 3H), 2.46- 2.42 (m, 1H), 1.80-1.68 (m, 5H), 1.40-1.21 (m, 5H). LC-MS: m/z 449.2 (M + H)+. 550 55 XII.89 [01183] 1H NMR (400 MHz, DMSO-d6): δ 13.1 (bs, 1H), 9.1 (bs, 1H), 7.39 (dd, J1 = 2.8 & J2 = 9.2 Hz, 2H), 7.20-7.13 (m, 4H), 7.08-7.05 (m, 1H), 6.98-6.90 (m, 3H), 3.72 (s, 3H), 1.79-1.67 (m, 5H), 1.40-1.33 (m, 5H), one proton merged in DMSO. LC-MS: m/z 452.1 (M + H)+. 551 56 XII.90 [01184] 1H NMR (400 MHz, DMSO-d6): δ 13.07 (bs, 1H), 8.95 (s, 1H), 7.27 (d, J = 3.2 Hz, 1H), 7.23 (dd, J1 = 6.8 Hz & J2 = 8.8 Hz, 2H), 7.13 (d, J = 8.4 Hz, 1H), 7.03 (dd, J1 = 3.2 Hz & J2 = 9.2 Hz, 1H), 6.94-6.89 (m, 3H), 6.82- 6.76 (m, 2H), 3.70 (s, 3H), 3.21 (s, 3H), 3.21 (s, 3H), 1.98 (s, 3H), 1.84 (s, 6H), 1.69 (s, 6H). LC-MS: m/z 497.3 (M + H)+. 552 57 XII.91 [01185] 1H NMR (400 MHz, DMSO-d6): δ 13.1 (s, 1H), 9.11 (s, 1H), 7.38 (d, J = 2.8 Hz, 1H), 7.14- 7.05 (m, 6H), 6.98 (d, J = 8.8 Hz, 2H), 6.86 (d, J = 8 Hz, 2H), 3.71 (s, 3H), 3.20 (s, 3H), 2.67- 2.59 (m, 1H), 2.08-1.83 (m, 6H), 1.66-1.56 (m, 2H). LC-MS: m/z 467.2 (M + H)+. 553 58 XII.92 [01186] 1H NMR (400 MHz, DMSO-d6): δ 13.06 (bs, 1H), 9.07 (bs, 1H), 7.37 (s, 1H), 7.08-7.0 (m, 8H), 6.87 (d, J = 7.6 Hz, 2H), 4.70 (q, J = 8.8 Hz, 2H), 3.71 (s, 3H), 3.19 (s, 3H). LC-MS: m/z 447 (M + H)+. 554 59 XII.93 [01187] 1H NMR (400 MHz, DMSO-d6): δ 13.0 (bs, 1H), 9.1 (bs, 1H), 7.37 (d, J = 2.8 Hz, 1H), 7.11- 7.06 (m, 6H), 6.95-6.85 (m, 4H), 3.71 (s, 3H), 3.19 (s, 3H), 2.23 (s, 3H). LC-MS: m/z 363.1 (M + H)+. 555 60 XII.94 [01188] 1H NMR (400 MHz, DMSO-d6): δ 13.2 (s, 1H), 11.73 (s, 1H), 9.1 (s, 1H), 7.59 (brm, 2H), 7.40-7.12 (brm, 7H), 6.84 (brm, 2H), 3.73 (s, 3H), 3.41-3.25 (brm, 7H), 2.01-1.77 (brm, 5H), 1.53 (brm, 1H). LC-MS: m/z 432.4 (M + H)+. 556 61 XII.95 [01189] 1H NMR (400 MHz, DMSO-d6): δ 13.1 (bs, 1H), 9.12 (bs, 1H), 7.37 (d, J = 3.2 Hz, 1H), 7.13- 7.04 (m, 6H), 6.96 (d, J = 8.8 Hz, 2H), 6.89 (d, J = 8.4 Hz, 2H), 3.71 (s, 3H), 3.45-3.41 (m, 1H), 3.20 (s, 3H), 2.25-2.22 (m, 2H), 2.07-1.91 (m, 3H), 1.82-1.77 (m, 1H). LC-MS: m/z 403.2 (M + H)+. 557 62 XII.96 [01190] 1H NMR (400 MHz, DMSO-d6): δ 13.15 (bs, 1H), 9.18 (bs, 1H), 7.39 (d, J = 2.8 Hz, 1H), 7.30 (d, J = 8.8 Hz, 2H), 7.20- 7.14 (m, 3H), 7.10-7.05 (m, 3H), 6.82 (d, J = 8.8 Hz, 2H), 5.87 (bs, 1H), 3.72 (s, 3H), 3.23 (s, 3H), 2.73-2.61 (m, 4H), 2.18- 2.11 (m, 2H). LC-MS: m/z 465.2 (M + H)+. 558 63 XII.97 [01191] 1H NMR (400 MHz, DMSO-d6): δ 10.24 (bs, 1H), 8.32 (d, J = 2.8 Hz, 1H), 8.21 (d, J = 7.6 Hz, 1H), 7.59 (d, J = 8.8 Hz, 2H), 7.08 (d, J = 8.8 Hz, 2H), 6.98 (d, J = 8.8 Hz, 2H), 6.85-6.78 (m, 3H), 3.21 (s, 3H), 2.40-2.32 (m, 1H), 1.78-1.67 (m, 5H), 1.37-1.23 (m, 5H). LC-MS: m/z 402.3 (M + H)+. 560 64 XII.99 [01192] 1H NMR (400 MHz, DMSO-d6): δ 13.04 (s, 1H), 8.94 (s, 1H), 7.37 (d, J = 2.4 Hz, 1H), 7.13- 7.10 (m, 3H), 7.04-7.01 (m, 1H), 6.92-6.88 (m, 3H), 6.81-6.75 (m, 2H), 3.70 (s, 3H), 3.21 (s, 3H), 2.42-2.40 (m, 1H), 2.12 (s, 3H), 1.78-1.67 (m, 5H), 1.40-1.23 (m, 4H), 1.22 (s, 1H). LC-MS: m/z 445.3 (M + H)+. 561 65 XII.100 [01193] 1H NMR (400 MHz, DMSO-d6): δ 13.0 (s, 1H), 9.39 (s, 1H), 7.87 (dd, J1 = 2 Hz & J2 = 8.0 Hz, 1H), 7.49 (d, J = 2.4 Hz, 1H), 7.36-7.26 (m, 3H), 7.05 (d, J = 8.4 Hz, 1H), 6.97 (d, J = 2.4 Hz, 1H), 6.79-6.68 (m, 3H), 2.16 (s, 3H), 1.69-1.18 (m, 13H), 0.85 (s, 6H). LC-MS: m/z 515.15 (M + H)+. 563 66 XII.101 [01194] 1H NMR (400 MHz, DMSO-d6): δ 13.21 (s, 1H), 9.13 (s, 1H), 7.46 (d, J = 8.8 Hz, 2H), 7.41 (d, J = 2.8 Hz, 1H), 7.32 (d, J = 8.4 Hz, 1H), 7.16 (d, J = 2.4 Hz, 1H), 7.11- 7.04 (m, 3H), 6.83 (d, J = 8.8 Hz, 2H), 3.73 (s, 3H), 3.28 (s, 3H), 2.21 (s, 3H). LC-MS: m/z 431.1 (M + H)+. 564 67 XII.102 [01195] 1H NMR (400 MHz, DMSO-d6) δ 13.1 (s, 1H), 9.0 (s, 1H), 7.48 (d, J = 2.4 Hz, 1H), 7.33 (dd, J1 = 2.0 Hz, J2 = 2.4 Hz, 3H), 7.05-6.94 (m, 3H), 6.81-6.73 (m, 2H), 3.71 (s, 3H), 2.14 (s, 3H), 1.69 (s, 2H), 1.52-1.18 (m, 11H), 0.86-0.84 (m, 6H). LC-MS: m/z 547.2 (M + 2)+ 565 68 XII.103 [01196] 1H NMR (400 MHz, DMSO-d6) δ 13.05 (bs, 1H), 8.91 (s, 1H), 7.36 (d, J = 2.8 Hz, 1H), 7.08 (d, J = 8.4 Hz, 1H), 7.05- 6.95 (m, 5H), 6.81 (s, 1H), 6.71-6.68 (m, 2H), 4.74-4.67 (m, 2H), 3.69 (s, 3H), 3.20 (s, 3H), 2.09 (s, 3H). LC-MS: m/z 461.2 (M + H)+. 566 69 XII.104 [01197] 1H NMR (400 MHz, DMSO-d6) δ 13.06 (s, 1H), 9.45 (s, 1H), 8.03 (d, J = 2.4 Hz, 1H), 7.89- 7.87 (m, 1H), 7.80 (dd, J1 = 2.4 Hz, J2 = 8.8 Hz, 1H), 7.40-7.34 (m, 2H), 7.26-7.20 (m, 2H), 7.10 (d, J = 8.4 Hz, 1H), 6.94 (d, J = 8.4 Hz, 1H), 6.76 (t, J = 7.2 Hz, 1H), 2.58- 2.52 (m, 1H), 1.80-1.68 (m, 5H), 1.46-1.23 (m, 5H). LC-MS: m/z 423.1 (M + H)+. 567 70 XIII.12 [01198] 1H NMR (400 MHz, CDCl3): δ 7.55 (d, J = 3.2 Hz, 1H), 7.33 (d, J = 8.4 Hz, 2H), 7.24 (s, 1H), 7.16-7.14 (m, 2H), 7.08- 7.06 (m, 2H), 7.03-7.0 (m, 1H), 6.76 (d, J = 8.4 Hz, 2H), 4.07 (s, 2H), 3.80 (s, 3H), 3.5 (s, 2H), 3.25 (s, 3H), 2.56 (s, 3H), 2.73 (s, 2H), 1.82 (s, 4H). LC-MS: m/z 446.2 (M + H)+ 568 71 XII.106 [01199] 1H NMR (400 MHz, DMSO-d6): δ 13.15 (s, 1H), 8.9 (s, 1H), 7.36 (d, J = 2.8 Hz, 1H), 7.22-7.02 (m, 6H), 6.76 (d, J = 8.8 Hz, 1H), 6.67 (dd, J1 = 2.4 Hz & J2 = 13.6 Hz, 1H), 6.54 (dd, J1 = 2.4 Hz & J2 = 8.8 Hz, 1H), 4.75 (q, J = 8.8 Hz, 2H), 3.70 (s, 3H), 3.21 (s, 3H). LC-MS: m/z 465.1 (M + H)+. 569 72 XII.107 [01200] 1H NMR (400 MHz, DMSO-d6): δ 13.13 (s, 1H), 9.22 (s, 1H), 7.49- 7.45 (m, 2H), 7.35 (d, J = 2.8 Hz, 1H), 7.27 (dd, J1 = 1.6 & J2 = 8, 1H), 7.15 (d, J = 8.8 Hz, 1H), 7.08 (dd, J1 = 2.8 Hz & J2 = 9.2, 1H), 7.01-6.96 (m, 2H), 6.68 (dd, J1 = 3.2 Hz & J2 = 10, 1H), 3.71 (s, 3H), 2.13 (s, 1H), 1.66 (s, 2H), 1.5-1.3 (m, 8H), 1.17 (s, 2H), 0.88 (s, 6H). LC-MS: m/z 550.2 (M + H)+. 570 73 XII.107 [01201] 1H NMR (400 MHz, DMSO-d6): δ 13.26 (s, 1H), 9.11 (s, 1H), 7.50 (d, J = 2 Hz, 1H), 7.42- 7.34 (m, 3H), 7.11-7.06 (m, 2H), 7.01-6.94 (m, 2H), 6.72 (d, J = 8.8 Hz, 1H), 3.72 (s, 3H), 2.14 (s, 1H), 1.69 (s, 2H), 1.53- 1.33 (m, 8H), 1.23-1.18 (m, 2H), 0.86 (s, 6H). LC-MS: m/z 550.2 (M + H)+ 571 74 XII.108 [01202] 1H NMR (400 MHz, DMSO-d6): δ 13.4 (bs, 1H), 9.14 (s, 1H), 7.62 (d, J = 9.2 Hz, 2H), 7.42 (d, J = 2.4 Hz, 1H), 7.33 (d, J = 8.4 Hz, 1H), 7.18 (d, J = 2 Hz, 1H), 7.12- 7.06 (m, 3H), 6.76 (d, J = 8.8 Hz, 2H), 3.74 (s, 3H), 3.29 (s, 3H), 2.22 (s, 3H). LC-MS: m/z 489.1 (M + H)+. 572 75 XII.109 [01203] 1H NMR (400 MHz, DMSO-d6): δ 13.35 (s, 1H), 9.25 (s, 1H), 7.51 (d, J = 8.8 Hz, 2H), 7.46- 7.41 (m, 2H), 7.23-7.11 (m, 3H), 7.03-7.01 (m, 1H), 6.93 (d, J = 8.8 Hz, 2H), 3.74 (s, 3H), 3.30 (s, 3H). LC-MS: m/z 435.1 (M + H)+. 573 76 XII.110 [01204] 1H NMR (400 MHz, DMSO-d6): δ 13.4 (bs, 1H), 9.27 (s, 1H), 7.65 (d, J = 9.2 Hz, 2H), 7.48- 7.43 (m, 2H), 7.28-7.11 (m, 3H), 7.05 (d, J = 8.4 Hz, 1H), 6.85 (d, J = 9.2 Hz, 2H), 3.75 (s, 3H), 3.30 (s, 3H). LC-MS: m/z 493.1 (M + H)+. 574 77 XII.111 [01205] 1H NMR (400 MHz, DMSO-d6): δ 13.30- 12.80 (bs, 1H), 9.11 (s, 1H), 7.37 (d, J = 2.8 Hz, 1H), 7.15-7.07 (m, 6H), 6.98-6.95 (m, 2H), 6.90- 6.87 (m, 2H), 3.71 (S, 3H), 3.21 (s, 3H), 1.91- 1.88 (m, 1H), 1.80-1.30 (m, 9H), 1.0 (d, J = 6.8 Hz, 3H). LC-MS: m/z 445.3 (M + H)+. 575 78 XII.112 [01206] 1H NMR (400 MHz, DMSO-d6): δ 13.2 (s, 1H), 9.2 (s, 1H), 7.8 (s, 1H), 7.53 (d, J = 8.8 Hz, 1H), 7.40 (d, J = 2.8 Hz, 1H), 7.24-7.20 (m, 3H), 7.16-6.88 (m, 5H), 3.73 (s, 3H). LC-MS: m/z 420.2 (M + H)+. 576 79 XII.113 [01207] 1H NMR (400 MHz, DMSO-d6) δ 13.24 (s, 1H), 9.20 (s, 1H), 8.46 (s, 1H), 7.67 (dd, J1 = 2.0 Hz, J2 = 8.8 Hz, 1H), 7.42 (d, J = 2.8 Hz, 1H), 7.34 (d, J = 8.8 Hz, 1H), 7.24 (m, 4H), 7.12 (dd, J1 = 3.6 Hz, J2 = 9.2 Hz, 1H), 6.49 (d, J = 8.8 Hz, 1H), 3.74 (s, 3H), 3.41 (s, 3H). LC- MS: m/z 471.66 (M + H)+ 577 80 XII.114 [01208] 1H NMR (400 MHz, DMSO-d6) δ 13.1 (s, 1H), 8.90 (s, 1H), 7.37 (d, J = 3.6 Hz, 1H), 7.11 (d, J = 8.4 Hz, 3H), 7.02 (dd, J1 = 3.2 Hz, J2 = 9.2 Hz, 1H), 6.92-6.88 (m, 3H), 6.81-6.75 (m, 2H), 3.70 (s, 3H), 3.21 (s, 3H), 2.67-2.65 (m, 1H), 2.32- 2.31 (m, 1H), 2.22 (s, 1H), 2.11 (s, 3H), 1.71- 1.40 (m, 4H), 1.40-1.11 (m, 4H). LC-MS: m/z 456.15 (M + H)+ 578 81 XII.115 [01209] 1H NMR (400 MHz, DMSO-d6) δ 13.30 (s, 1H), 9.18 (s, 1H), 7.98 (d, J = 2.4 Hz, 1H), 7.56 (d, J = 10 Hz, 2H), 7.41 (d, J = 2.8 Hz, 1H), 7.30- 7.17 (m, 5H), 7.13-7.10 (m, 1H), 3.74 (s, 3H), 3.30 (s, 3H), 1.25-1.21 (m, 7H), 1.10 (s, 4H). LC-MS: m/z 432.3 (M + H)+ 579 82 XII.116 [01210] 1H NMR (400 MHz, DMSO-d6) δ 13.45 (s, 1H), 9.61 (s, 1H), 8.09 (s, 1H), 7.60-7.57 (m, 1H), 7.17 (d, J = 8.4 Hz, 2H), 7.12 (d, J = 8.8 Hz, 1H), 7.01 (d, J = 8.8 Hz, 2H), 6.91 (d, J = 2.4 Hz, 1H), 6.77 (dd, J1 = 2.8 Hz, J2 = 8.8 Hz, 1H), 6.68 (d, J = 9.2 Hz, 1H), 3.24 (s, 3H), 2.46-2.42 (m, 1H), 2.09 (s, 3H), 1.80-1.68 (m, 5H), 1.43-1.23 (m, 5H). LC-MS: m/z 481.10 (M + H)+. 580 83 XII.117 [01211] 1H NMR (400 MHz, DMSO-d6) δ 13.38 (bs, 1H), 9.29 (s, 1H), 7.72 (s, 1H), 7.33 (dd, J1 = 2.4 Hz, J2 = 9.6 Hz, 1H), 7.14 (t, J = 8.4 Hz, 3H), 6.98 (d, J = 8.4 Hz, 2H), 6.91 (d, J = 1.6 Hz, 1H), 6.78 (dd, J1 = 1.6 Hz, J2 = 8.0 Hz, 1H), 6.67 (d, J = 9.2 Hz, 1H), 3.23 (s, 3H), 2.46- 2.42 (m, 1H), 2.10 (s, 3H), 1.79-1.68 (m, 5H), 1.39-1.20 (m, 5H). LC- MS: m/z 498.15 (M + H)+ 581 84 XII.118 [01212] 1H NMR (400 MHz, DMSO-d6) δ 13.28 (s, 1H), 9.20 (s, 1H), 7.85 (s, 1H), 7.67 (s, 1H), 7.42 (d, J = 3.2 Hz, 1H), 7.35- 7.23 (m, 5H), 7.14-7.11 (m, 1H), 6.70 (d, J = 6.70 Hz, 1H), 3.78 (s, 3H), 3.40 (s, 3H), 1.78-1.72 (m, 6H), 1.38-1.32 (m, 5H). LC-MS: m/z 432.60 (M + H)+ 582 85 XII.119 [01213] 1H NMR (400 MHz, DMSO-d6) δ 9.2 (s, 1H), 7.38 (d, J = 3.2 Hz, 1H), 7.15-7.07 (m, 6H), 6.99 (d, J = 8.8 Hz, 2H), 6.88 (d, J = 8.8 Hz, 2H 3.72 (s, 3H), 3.48 (brm, 2H), 3.21 (s, 3H), 3.08-2.99 (brm, 2H), 2.77 (s, 3H), 2.68 (brm, 1H), 2.0-1.8 (brm, 4H). LC-MS? m/z 445.24 (M + H)+. 583 86 Com- pound 319 [01214] 1H NMR (400 MHz, DMSO-d6) δ 13.12 (s, 1H), 9.10 (d, J = 5.2 Hz, 1H), 7.37 (d, J = 3.2 Hz, 1H), 7.15-7.07 (m, 6H), 6.98-6.95 (m, 2H), 6.88 (d, J = 8.8 Hz, 2H), 3.71 (s, 3H), 3.21 (s, 3H), 2.46-2.44 (m, 1H), 1.91- 1.88 (m, 1H), 1.72-1.45 (m, 8H), 1.00 (d, J = 7.2 Hz, 3H). LC-MS: m/z 445.2 (M + H)+ 584 87 Com- pound 319 [01215] 1H NMR (400 MHz, DMSO-d6) δ 13.20- 12.90 (bs, 1H), 9.21-8.95 (bs, 1H), 7.37 (d, J = 2.8 Hz, 1H), 7.11-7.04 (m, 6H), 6.96 (d, J = 8.8 Hz, 2H), 6.87 (d, J = 8.8 Hz, 2H), 3.71 (s, 3H), 3.20 (s, 3H), 2.40-2.32 (m, 1H), 1.80-1.74 (m, 4H), 1.42- 1.35 (m, 3H), 1.10-0.95 (m, 2H), 0.90 (d, J = 6.4 Hz, 3H). LC-MS: m/z 445.3 (M + H)+ 585 88 XII.120 [01216] 1H NMR (400 MHz, DMSO-d6) δ 13.15 (s, 1H), 8.95 (s, 1H), 7.37 (d, J = 3.6 Hz, 1H), 7.24- 7.18 (m, 3H), 7.06-7.03 (m, 3H), 6.82-6.74 (m, 2H), 6.64 (dd, J1 = 2.0 Hz, J2 = 8.4 Hz, 1H), 3.70 (s, 3H), 3.21 (s, 3H), 2.70- 2.67 (m, 1H), 2.33-2.26 (m, 2H), 1.72-1.69 (m, 1H), 1.62-1.42 (m, 4H), 1.40-1.11 (m, 4H). LC- MS: m/z 461.2 (M + H)+ 586 89 XII.121 [01217] 1H NMR (400 MHz, DMSO-d6) δ 13.3 (s, 1H), 10.55 (s, 1H), 9.50- 9.2 (brs, 1H), 8.0 (d, J = 8.4 Hz, 2H), 7.71 (dd, J1 = 8.8 Hz, J2 = 12.8 Hz, 3H), 7.52-7.51 (m, 1H), 7.47-7.33 (m, 4H), 7.14- 7.12 (m, 1H), 3.75 (s, 3H). LC-MS: m/z 431.1 (M + H)+ 587 90 XX.25 [01218] 1H NMR (400 MHz, DMSO-d6) δ 12.5 (s, 1H), 7.45 (d, J = 8.8 Hz, 2H), 7.31 (d, J = 2.8 Hz, 1H), 7.19-7.06 (m, 4H), 6.88 (d, J = 8.8 Hz, 2H), 6.77 (d, J = 8.8 Hz, 2H) 3.79 (s, 3H), 3.25 (s, 3H). LC-MS: m/z 418.2 (M + H)+ 588 91 XII.123 [01219] 1H NMR (400 MHz, DMSO-d6) δ 13.50- 12.90 (brs, 1H), 9.60- 9.10 (brs, 1H), 7.42-7.32 (m, 5H), 7.23 (d, J = 8.8 Hz, 2H)), 7.12 (dd, J1 = 2.8 Hz, J2 = 8.8 Hz, 1H), 3.75 (s, 3H), 3.42 (s, 3H). LC-MS: m/z 424.0 (M + H)+ 589 92 XII.124 [01220] 1H NMR (400 MHz, DMSO-d6) δ 13.2 (s, 1H), 9.09 (brs, 1H), 7.4 (d, J = 3.2 Hz, 1H), 7.32 (m, 1H), 7.25 (d, J = 8.8 Hz, 2H), 7.12-7.00 (m, 5H), 6.86-6.82 (m, 1H), 3.70 (s, 3H), 3.26 (s, 3H). LC-MS: m/z 451.2 (M + H)+ 590 93 XII.125 [01221] 1H NMR (400 MHz, DMSO-d6) δ 13.18 (s, 1H), 9.05 (s, 1H), 7.39 (d, J = 3.2 Hz, 1H), 7.25- 7.19 (m, 3H), 7.08-7.05 (m, 2H), 6.98-6.86 (m, 4H), 3.72 (s, 3H), 3.24 (s, 3H), 2.17 (s, 3H). LC-MS: m/z 447.2 (M + H)+ 591 94 XII.126 [01222] 1H NMR (400 MHz, DMSO-d6) δ 13.20 (bs, 1H), 9.08 (bs, 1H), 7.97 (d, J = 2.8 Hz, 1H), 7.73 (dd, J1 = 3.2 Hz, J2 = 9.2 Hz, 1H), 7.39-7.38 (m, 2H), 7.24-7.17 (m, 2H), 7.07-6.99 (m, 3H), 3.71 (s, 3H), 2.57-2.52 (m, 1H), 1.8-1.68 (m, 5H) 1.43-1.31 (m, 5H). LC- MS: m/z 453.2 (M + H)+ 592 95 XII.127 [01223] 1H NMR (400 MHz, DMSO-d6) δ 13.55- 12.95 (brs, 1H), 9.05 (s, 1H), 8.18 (d, J = 2.4 Hz, 1H), 7.64 (d, J = 8.4 Hz, 2H), 7.54 (dd, J1 = 2.4 Hz, J2 = 8.8 Hz, 1H), 7.39 (d, J = 2.8 Hz, 1H), 7.34 (d, J = 8.4 Hz, 2H), 7.09-7.02 (m, 3H), 3.72 (s, 3H), 3.44 (s, 3H). LC-MS: m/z 481.2 (M + H)+ 593 96 XII.128 [01224] 1H NMR (400 MHz, DMSO-d6) δ 13.11 (s, 1H), 9.20 (s, 1H), 7.37 (d, J = 2.8 Hz, 1H), 7.14- 7.03 (m, 6H), 6.98-6.86 (m, 4H), 3.71 (s, 3H), 3.20 (s, 3H), 2.33-2.32 (m, 1H), 1.58-1.42 (m, 6H), 1.33-1.29 (m, 2H), 0.95-0.93 (m, 6H). LC- MS: m/z 459.3 (M + H)+ 594 97 XII.129 [01225] 1H NMR (400 MHz, DMSO-d6) δ 13.2-13.0 (brs, 1H), 9.0-8.7 (bs, 1H), 8.29 (s, 2H), 7.37 (d, J = 2.8 Hz, 1H), 7.23 (dd, J1 = 8.8 Hz, J2 = 11.6 Hz, 4H), 6.99 (dd, J1 = 3.2 Hz, J2 = 9.6 Hz, 1H), 6.73 (d, J = 8.8 Hz, 1H), 3.69 (s, 3H), 3.44 (s, 3H), 1.81-1.69 (m, 6H), 1.43- 1.35 (m, 5H) LC-MS: m/z 433.2 (M + H)+ 595 98 XII.130 [01226] 1H NMR (400 MHz, DMSO-d6) δ 13.15 (s, 1H), 9.05 (bs, 1H), 8.18 (d, J = 2.8 Hz, 1H), 7.79 (d, J = 9.2 Hz, 2H), 7.63 (dd, J1 = 2.8 Hz, J2 = 8.8 Hz, 1H), 7.40 (t, J = 1.6 Hz, 1H), 7.29 (d, J = 8.8 Hz, 2H), 7.12 (d, J = 9.2 Hz, 1H), 7.09 (d, J = 1.6 Hz, 2H). 3.37 (s, 3H), 3.44 (s, 3H), LC-MS: m/z 476.1 (M + H)+. 596 99 XII.131 [01227] 1H NMR (400 MHz, DMSO-d6) δ 13.2 (s, 1H), 9.0 (s, 1H), 8.09 (d, J = 2.4 Hz, 1H), 7.44 (dd, J1 = 2.8 Hz, J2 = 8.8 Hz, 1H), 7.39-7.37 (m, 5H), 7.02 (dd, J1 = 3.2 Hz, J2 = 9.2 Hz, 1H), 6.88 (d, J = 8.8 Hz, 1H), 6.74 (d, J = 9.6 Hz, 1H), 3.70 (s, 3H), 3.39 (s, 3H). LC-MS: m/z 434.1 (M + H)+ 597 100 XII.132 [01228] 1H NMR (400 MHz, DMSO-d6) δ 9.2 (s, 1H), 7.42-7.38 (m, 3H), 7.33 (d, J = 9.2 Hz, 1H) 7.22 (d, J = 8.8 Hz, 2H), 7.15- 7.12 (m, 1H), 6.39 (s, 1H), 3.84 (s, 3H), 3.48 (s, 3H), 1.98-1.95 (m, 2H), 1.96-1.66 (m, 3H), 1.35- 1.16 (m, 6H). LC-MS: m/z 438.2 (M + H)+ 598 101 XII.133 [01229] 1H NMR (400 MHz, DMSO-d6) δ 13.60-12.80 (brs, 1H), 8.91 (s, 1H), 7.97 (s, 1H), 7.60 (s, 1H), 7.38-7.27 (m, 5H), 7.05 (dd, J1 = 2.8 Hz, J2 = 9.2 Hz, 1H), 6.87 (d, J = 9.2 Hz, 1H), 6.69 (d, J = 8.8 Hz, 1H), 3.71 (s, 3H), 3.42 (s, 3H), 1.75-1.65 (m, 5H), 1.50-1.10 (m, 6H) LC-MS: m/z 432.2 (M + H)+ 599 102 XII.134 [01230] 1H NMR (400 MHz, DMSO-d6) δ 13.15 (bs, 1H), 8.92 (s, 1H), 7.94 (s, 1H), 7.39-7.37 (m, 2H), 7.24-7.17 (m, 2H), 7.08 (s, 1H), 7.01 (dd, J1 = 3.2 Hz, J2 = 9.2 Hz, 1H), 6.57 (d, J = 9.2 Hz, 1H), 3.69 (s, 3H), 2.57-2.53 (m, 1H), 2.19 (s, 3H), 1.81- 1.68 (m, 5H), 1.43-1.33 (m, 5H). LC-MS: m/z 467.1 (M + H)+ 600 103 XII.135 [01231] 1H NMR (400 MHz, DMSO-d6) δ 13.10 (s, 1H), 9.06 (s, 1H), 8.00 (d, J = 2.0 Hz, 1H), 7.77- 7.74 (m, 2H), 7.43 (s, 2H), 7.39 (s, 1H), 7.14 (d, J = 8.0 Hz, 1H), 7.04 (d, J = 9.2 Hz, 2H), 3.72 (s, 3H). LC-MS: m/z 455.0 (M + H)+. 601 104 XII.136 [01232] 1H NMR (400 MHz, DMSO-d6) δ 13.3 (s, 1H), 9.1 (s, 1H), 8.04- 8.01 (m, 2H), 7.80-7.75 (m, 2H), 7.47 (d, J = 8.8 Hz, 1H), 7.40 (s, 1H), 7.10-7.05 (m, 2H), 3.72 (s, 3H). LC-MS: m/z 439.5.1 (M + H)+ 602 105 XII.137 [01233] 1H NMR (400 MHz, DMSO-d6) δ 13.16 (s, 1H), 8.90 (s, 1H), 8.39 (s, 2H), 7.71 (d, J = 8.4 Hz, 2H), 7.62 (d, J = 8.8 Hz, 2H), 7.38 (d, J = 3.2 Hz, 1H), 7.06-7.02 (m, 1H), 6.87-6.83 (m, 1H), 3.71 (s, 3H), 3.55 (s, 3H). LC- MS: m/z 410.10 (M + H)+ 603 106 XII.138 [01234] 1H NMR (400 MHz, DMSO-d6) δ 7.39 (d, J = 2.8 Hz, 2H), 7.13-7.09 (m, 6H), 6.98 (d, J = 8.8 Hz, 2H), 6.86 (d, J = 8.4 Hz, 2H), 3.71 (s, 3H), 3.20 (s, 3H), 2.60-2.40 (m, 1H), 1.76-1.70 (m, 10H). LC-MS: m/z 498.25 (M + H)+ 609 107 XII.139 [01235] 1H NMR (400 MHz, DMSO-d6) δ 13.00 (s, 1H), 8.74 (s, 1H), 7.97 (s, 1H), 7.35 (d, J = 3.2 Hz, 1H), 7.27 (d, J = 8.0 Hz, 2H), 7.21 (d, J = 8.4 Hz, 2H), 6.99 (dd, J1 = 2.8 Hz, J2 = 8.8 Hz, 1H), 6.49 (s, 1H), 6.44 (d, J = 9.6 Hz, 1H), 3.69 (s, 3H), 3.36 (s, 3H), 1.96 (s, 3H), 1.81- 1.69 (m, 5H), 1.43-1.23 (m, 6H). LC-MS: m/z 446.3 (M + H)+. 612 108 XII.140 [01236] 1H NMR (400 MHz, DMSO-d6) δ 13.22 (s, 1H), 9.20 (s, 1H), 7.40 (d, J = 2.8 Hz, 1H), 7.31 (d, J = 9.2 Hz, 1H), 7.23- 7.01 (m, 5H), 6.80 (s, 1H), 6.61 (d, J = 1.2 Hz, 2H), 3.74 (s, 3H), 3.22 (s, 3H). LC-MS: m/z 417.1 (M + H)+. 613 109 XII.141 [01237] 1H NMR (400 MHz, DMSO-d6) δ 13.26 (s, 1H), 9.51 (s, 1H), 9.39 (s, 1H), 7.79 (d, J = 2.0 Hz, 1H), 7.47 (d, J = 8.8 Hz, 2H), 7.33-7.21 (m, 6H), 6.85 (d, J = 8.8 Hz, 2H), 3.30 (s, 3H), 2.91 (s, 3H). LC-MS: m/z 480.1 (M + H)+. 614 110 XII.142 [01238] 1H NMR (400 MHz, DMSO-d6) δ 13.42 (s, 1H), 9.70 (s, 1H), 8.25 (d, J = 2.0 Hz, 1H), 7.62 (dd, J1 = 2.0 Hz, J2 = 8.8 Hz, 1H), 7.22-7.12 (m, 4H), 7.02 (d, J = 8.0 Hz, 2H), 6.90 (d, J = 2.4 Hz, 1H), 6.77 (dd, J1 = 2.4 Hz, J2 = 8.4 Hz, 1H), 6.69 (d, J = 8.8 Hz, 1H), 3.25 (s, 3H), 2.37 (d, J = 5.2 Hz, 3H), 2.10 (s, 3H), 1.80- 1.68 (m, 5H), 1.40-1.23 (m, 6H). LC-MS: 508.2 (M + H)+. 615 111 XII.143 [01239] 1H NMR (400 MHz, DMSO-d6) δ 13.24 (s, 1H), 9.08 (s, 1H), 8.24 (d, J = 2.8 Hz, 1H), 8.03 (d, J = 2.8 Hz, 1H), 7.96- 7.93 (m, 1H), 7.80-7.77 (m, 1H), 7.48 (d, J = 9.2 Hz, 1H), 7.40 (d, J = 2.0 Hz, 1H), 7.20 (d, J = 8.4 Hz, 1H), 7.09-7.08 (m, 2H), 3.73 (s, 3H). LC-MS: m/z 497.0 (M + H)+. 616 112 XII.144 [01240] 1H NMR (400 MHz, DMSO-d6) δ 11.94-11.83 (bs, 1H), 8.41 (s, 2H), 7.50 (d, J = 2.4 Hz, 1H), 7.39 (s, 1H), 7.24 (s, 2H), 7.03 (d, J = 8.8 Hz, 1H), 6.79-6.76 (m, 1H), 3.77 (s, 3H), 3.60-3.50 (m, 1H), 1.91-1.68 (m, 5H), 1.51-1.22 (m, 5H), LC-MS: m/z 454.1 (M + H)+. 617 113 XII.145 [01241] 1H NMR (400 MHz, DMSO-d6) δ 13.70- 12.80 (bs, 1H), 9.80-8.90 (bs, 1H), 7.54-7.51 (m, 1H), 7.42 (d, J = 3.2 Hz, 1H), 7.32 (d, J = 9.2 Hz, 1H), 7.25-7.09 (m, 5H), 6.81 (d, J = 2.4 Hz, 1H), 6.68-6.65 (m, 1H), 3.74 (s, 3H), 3.28 (s, 3H). LC-MS: m/z 451.2 (M + H)+ 618 114 XII.146 [01242] 1H NMR (400 MHz, DMSO-d6) δ 13.40- 12.80 (bs, 1H), 9.30-8.80 (bs, 1H), 7.34 (d, J = 2.8 Hz, 1H), 7.08-6.95 (m, 4H), 6.60-6.58 (m, 2H), 5.89 (s, 1H), 3.69 (s, 3H), 3.43 (s, 3H), 3.16 (s, 3H), 1.91-1.89 (m, 2H), 1.75- 1.72 (m, 3H), 1.37-1.23 (m, 6H). LC-MS: m/z 435.2 (M + H)+ 619 115 XII.147 [01243] 1H NMR (400 MHz, DMSO-d6) δ 13.05 (bs, 1H), 8.96 (s, 1H), 7.54 (d, J = 2.8 Hz, 1H), 7.12- 7.08 (m, 3H), 7.05 (dd, J1 = 2.8 Hz, J2 = 8.8 Hz, 1H), 6.90-6.87 (m, 3H), 6.79-6.72 (m, 2H), 3.78- 3.72 (m, 1H), 3.19 (s, 3H), 2.46-2.40 (m, 1H), 2.10 (s, 3H), 1.76-1.66 (m, 5H), 1.39-1.28 (m, 5H), 0.72-0.70 (m, 2H), 0.69-0.66 (m, 2H). LC- MS: m/z 471.2 (M + H)+. 620 116 XII.148 [01244] 1H NMR (400 MHz, DMSO-d6) δ 8.67 (s, 1H), 7.14-7.04 (m, 4H), 6.92-6.88 (m, 2H), 6.84- 6.75 (m, 5H), 3.84 (d, J = 10.4 Hz, 2H), 3.40- 3.34 (m, 3H), 3.17 (s, 3H), 2.43-2.38 (m, 1H), 2.12 (s, 3H), 1.89-1.65 (m, 6H), 1.35-1.17 (m, 8H). LC-MS: m/z 514.3 (M + H)+. 621 117 XII.149 [01245] 1H NMR (400 MHz, DMSO-d6) δ 13.00- 12.90 (bs, 1H), 8.96 (s, 1H), 7.38 (d, J = 2.8 Hz, 1H), 7.14-7.10 (m, 4H), 6.93-6.88 (m, 3H), 6.81- 6.77 (m, 2H), 3.76-3.71 (m, 4H), 3.21 (s, 3H), 2.96-2.94 (m, 4H), 2.46- 2.39 (m, 1H), 2.12 (s, 3H), 1.78-1.76 (m, 4H), 1.38-1.30 (m, 6H). LC-MS: m/z 499.2 (M + H)+. 622 118 XII.150 [01246] 1H NMR (400 MHz, DMSO-d6) δ 13.20 (s, 1H), 9.20 (s, 1H), 7.46- 7.41 (m, 3H), 7.30 (d, J = 7.2 Hz, 1H), 7.23-7.10 (m, 5H), 6.77 (d, J = 8.8 Hz, 2H), 3.74 (s, 3H), 3.27 (s, 3H), LC-MS: m/z 449.1 (M + H)+ 623 119 XII.153 [01247] 1H NMR (400 MHz, DMSO-d6) δ 13.00 (s, 1H), 9.30 (s, 1H), 7.33- 7.26 (m, 3H), 7.05 (dd, J1 = 2.8 Hz, J2 = 9.2 Hz, 1H), 6.94-6.87 (m, 4H), 6.48 (d, J = 8.8 Hz, 2H), 3.69 (s, 3H), 3.08 (s, 3H), 2.32-2.20 (m, 1H), 1.86- 1.60 (m, 5H), 1.40-1.10 (m, 6H), 0.90-0.82 (m, 2H), 0.60-0.56 (m, 2H). LC-MS: m/z 471.2 (M + H)+. 624 120 XII.151 [01248] 1H NMR (400 MHz, DMSO-d6) δ 13.2-12.8 (bs, 1H), 9.40-8.80 (bs, 1H), 7.36 (d, J = 1.6 Hz, 1H), 7.11 (d, J = 8.8 Hz, 2H), 7.03 (s, 2H), 6.68 (d, J = 8.8 Hz, 2H), 6.63 (s, 1H), 3.70 (s, 3H), 3.59 (s, 3H), 3.22 (s, 3H). LC- MS: m/z 421.2 (M + H)+ 625 121 XII.152 [01249] 1H NMR (400 MHz, DMSO-d6) δ 13.26 (bs, 1H), 9.10 (s, 1H), 7.56 (dd, J1 = 3.2 Hz, J2 = 9.6 Hz, 1H), 7.23-7.22 (m, 1H), 7.14-7.11 (m, 3H), 6.96-6.91 (m, 3H), 6.79 (dd, J1 = 2.8 Hz, J2 = 8.8 Hz, 1H), 6.69-6.65 (m, 1H), 3.32 (s, 3H), 2.49- 2.43 (m, 1H), 2.10 (s, 3H), 1.79-1.67 (m, 5H), 1.38-1.22 (m, 5H). LC- MS: m/z 433.2 (M + H)+. 626 122 XII.153 [01250] 1H NMR (400 MHz, DMSO-d6) δ 13.20 (bs, 1H), 9.30 (s, 1H), 7.38- 7.36 (m, 1H), 7.16 (d, J = 8.4 Hz, 1H), 7.09-7.02 (m, 3H), 6.95 (d, J = 9.2 Hz, 1H), 6.84 (d, J = 8.4 Hz, 2H), 6.78 (dd, J1 = 2.8 Hz, J2 = 8.4 Hz, 1H), 6.65 (d, J = 2.8 Hz, 1H), 3.71 (s, 3H), 3.19 (s, 3H), 2.49-2.43 (m, 1H), 1.83- 1.67 (m, 6H), 1.37-1.21 (m, 5H), 0.86 (dd, J1 = 1.6 Hz, J2 = 8.0 Hz, 2H), 0.57-0.53 (m, 2H). LC- MS: m/z 470.2 (M+)+. 627 123 XII.154 [01251] 1H NMR (400 MHz, DMSO-d6) δ 8.79 (bs, 1H), 7.10-7.08 (m, 3H), 6.92-6.79 (m, 6H), 6.64- 6.62 (m, 1H), 4.69 (s, 4H), 3.88 (s, 4H), 3.19 (s, 3H), 2.46-2.40 (m, 1H), 2.11 (s, 3H), 1.78-1.67 (m, 5H), 1.37-1.29 (m, 5H). LC-MS: m/z 511.25 (M + H)+. 628 124 XII.155 [01252] 1H NMR (400 MHz, DMSO-d6) δ 13.10- 13.00 (bs, 1H), 8.90-9.10 (bs, 1H), 7.36 (d, J = 3.2 Hz, 1H), 7.14-7.10 (m, 3H), 7.02 (dd, J1 = 2.8 Hz, J2 = 9.2 Hz, 1H), 6.93- 6.88 (m, 3H), 6.81-6.74 (m, 2H), 3.89 (t, J = 6.4 Hz, 2H), 3.21 (s, 3H), 2.45-2.30 (m, 1H), 2.12 (s, 3H), 1.78-1.64 (m, 6H), 1.43-1.33 (m, 8H), 0.94 (t, J = 4.4 Hz, 3H). LC-MS: m/z 486.2 (M + H)+. 630 125 XII.156 [01253] 1H NMR (400 MHz, DMSO-d6) δ 12.83 (bs, 1H), 9.12 (s, 1H), 7.59 (d, J = 2.0 Hz, 1H), 7.12 (d, J = 8.8 Hz, 3H), 7.05 (dd, J1 = 2.0, J2 = 8.4 Hz, 1H), 6.93-6.91 (m, 3H), 6.79 (dd, J1 = 2.4 Hz, J2 = 8.4 Hz, 1H), 6.65 (d, J = 8.0 Hz, 1H), 3.21 (s, 3H), 2.46-2.42 (m, 1H), 2.10 (s, 3H), 1.92-1.67 (m, 6H), 1.41-1.33 (m, 5H), 0.86-0.82 (m, 2H), 0.54-0.51 (m, 2H). LC-MS: m/z 455.3 (M + H)+. 631 126 XII.157 [01254] 1H NMR (400 MHz, DMSO-d6) δ 12.8 (bs, 1H), 9.14 (s, 1H), 7.67 (d, J = 1.6 Hz, 1H), 7.16 7.11 (m, 4H), 6.93-6.91 (m, 3H), 6.81-6.78 (m, 1H), 6.67-6.64 (m, 1H), 3.22 (s, 3H), 2.43 (s, 1H), 2.20 (s, 3H), 2.11 (s, 3H), 1.80-1.68 (m, 5H), 1.38- 1.23 (m, 5H). LC-MS: m/z 429.3 (M + H)+. 632 127 XII.158 [01255] 1H NMR (400 MHz, DMSO-d6) δ 13.2 (bs, 1H), 9.60 (s, 1H), 8.42 (d, J = 2.4 Hz, 1H), 8.24 (d, J = 4.8 Hz, 1H), 7.76 (dd, J1 = 2.0, J2 = 8.8 Hz, 1H), 7.17-7.12 (m, 3H), 6.99 (d, J = 8.4 Hz, 2H), 6.91 (d, J = 2.4 Hz, 1H), 6.78 (dd, J1 = 2.8 Hz, J2 = 8.8 Hz, 1H), 6.62 (d, J = 9.2 Hz, 1H), 3.24 (s, 3H), 2.73 (d, J = 4.8 Hz, 3H), 2.46-2.44 (m, 1H), 2.10 (s, 3H), 1.79-1.68 (m, 5H), 1.39-1.16 (m, 5H). LC-MS: m/z 472.4 (M + H)+. 633 128 XII.159 [01256] 1H NMR (400 MHz, DMSO-d6) δ 13.10- 13.00 (bs, 1H), 8.96 (s, 1H), 7.36 (d, J = 3.2 Hz, 1H), 7.12 (dd, J1 = 4.4 Hz, J2 = 8.4 Hz, 3H), 7.04 (dd, J1 = 4.0 Hz, J2 = 9.2 Hz, 1H), 6.93-6.89 (m, 3H), 6.81-6.74 (m, 2H), 3.48 (s, 2H), 3.21 (s, 3H), 2.33-2.32 (m, 1H), 2.12 (s, 3H), 1.79-1.68 (m, 6H), 1.41-1.17 (m, 4H), 0.99 (s, 9H). LC-MS: m/z 501.4 (M+)+ 634 129 XII.160 [01257] 1H NMR (400 MHz, DMSO-d6) δ 13.10- 12.90 (bs, 1H), 8.95 (s, 1H), 7.38 (d, J = 3.2 Hz, 1H), 7.12 (t, J = 8.0 Hz, 3H), 7.03 (dd, J1 = 2.8 Hz, J2 = 8.8 Hz, 1H), 6.92- 6.89 (m, 3H), 6.80 (dd, J1 = 2.4 Hz, J2 = 8.0 Hz, 1H), 6.74 (d, J = 8.8 Hz, 1H), 4.15-4.09 (m, 1H), 3.21 (s, 3H), 2.45-2.38 (m, 1H), 2.12 (s, 3H), 1.89-1.86 (m, 2H), 1.79- 1.68 (m, 4H), 1.55-1.24 (m, 14H). LC-MS: m/z 512.3 (M+)+. 635 130 XII.161 [01258] 1H NMR (400 MHz, DMSO-d6) δ 13.1 (s, 1H), 9.35 (s, 1H), 8.15 (s, 3H), 7.99 (d, J = 2.0 Hz, 1H), 7.41 (dd, J1 = 2.0 Hz, J2 = 8.8 Hz, 1H), 7.16- 7.09 (m, 3H), 6.97 (d, J = 8.8 Hz, 2H), 6.92 (d, J = 2.4 Hz, 1H), 6.79 (dd, J1 = 2.8 Hz, J2 = 8.8 Hz, 1H), 6.65 (d, J = 8.4 Hz, 1H), 3.92-3.87 (m, 2H), 3.23 (s, 3H), 2.40 (s, 1H), 2.10 (s, 3H), 1.79-1.68 (m, 5H), 1.39-1.22 (m, 5H). LC-MS: m/z 427.2 (M + H)+. 636 131 XII.162 [01259] 1H NMR (400 MHz, DMSO-d6) δ 8.33 (s, 1H), 7.61-7.59 (m, 1H), 7.38 (d, J = 8.4 Hz, 1H), 7.30 (d, J = 7.6 Hz, 1H), 7.11 (d, J = 8.8 Hz, 2H), 6.91-6.88 (m, 3H), 6.80- 6.78 (m, 1H), 6.72 (d, J = 8.0 Hz, 1H), 3.21 (s, 3H), 2.49-2.45 (m, 1H), 2.15 (s, 3H), 1.79-1.67 (m, 5H), 1.38-1.33 (m, 5H). LC-MS: m/z 416.3 (M + H)+. 637 132 XII.163 [01260] 1H NMR (400 MHz, DMSO-d6) δ 9.62-9.50 (bs, 1H), 8.90-8.70 (bs, 1H), 8.02 (d, J = 1.2 Hz, 1H), 7.40 (d, J = 8.0 Hz, 1H), 7.16-7.10 (m, 3H), 6.98-6.91 (m, 3H), 6.79 (dd, J1 = 2.8 Hz, J2 = 8.8 Hz, 1H), 6.67 (d, J = 8.8 Hz, 1H), 3.98 (s, 2H), 3.23 (s, 3H), 2.54 (s, 1H), 2.50 (s, 3H), 2.10 (s, 3H), 1.79-1.68 (m, 5H), 1.39- 1.23 (m, 5H). LC-MS: m/z 456.3 (M − H)+. 638 133 XV.49 [01261] 1H NMR (400 MHz, DMSO-d6) δ 13.00- 12.90 (bs, 1H), 10.12 (s, 1H), 8.57 (s, 1H), 8.40 (t, J = 2.0 Hz, 1H), 8.03 (d, J = 8.4 Hz, 1H), 7.87 (d, J = 8.8 Hz, 2H), 7.63 (d, J = 8.8 Hz, 1H), 7.46 (d, J = 8.0 Hz, 1H), 7.17 (d, J = 8.4 Hz, 2H), 7.11-7.05 (m, 4H), 2.46-2.42 (m, 1H), 1.81-1.78 (m, 5H), 1.42-1.32 (m, 5H). LC-MS: m/z 415.2 (M + H)+. 640 134 XII.164 [01262] 1H NMR (400 MHz, DMSO-d6) δ 8.09 (s, 1H), 7.18 (d, J = 8.4 Hz, 2H), 7.10 (d, J = 8.4 Hz, 2H), 6.92 (d, J = 2.4 Hz, 1H), 6.87 (d, J = 8.4 Hz, 2H), 6.82-6.77 (m, 2H), 3.72 (s, 2H), 3.20 (s, 3H), 2.43 (s, 3H), 2.50 (s, 3H), 2.14 (s, 3H), 1.78-1.67 (m, 5H), 1.40-1.32 (m, 5H). LC-MS: m/z 470.3 (M + H)+. 641 135 XII.165 [01263] 1H NMR (400 MHz, DMSO-d6) δ 8.38 (s, 1H), 7.68-7.64 (m, 1H), 7.37-7.31 (m, 3H), 7.17- 7.03 (M, 6H), 6.78 (s, 1H), 2.46 (s, 1H), 1.79- 1.68 (m, 5H), 1.39-1.16 (m, 5H). LC-MS: m/z 456.1 (M + H)+. 642 136 XII.166 [01264] 1H NMR (400 MHz, DMSO-d6) δ 10.00 (s, 1H), 8.57 (s, 1H), 8.20 (d, J = 8.4 Hz, 1H), 7.82- 7.66 (m, 5H), 7.47 (d, J = 7.6 Hz, 1H), 7.21-7.17 (m, 3H), 2.36 (s, 3H), 1.79-1.69 (m, 5H), 1.44- 1.21 (m, 6H). LC-MS: m/z 430.2 (M + H)+. 643 137 XII.167 [01265] 1H NMR (400 MHz, DMSO-d6) δ 12.80 (s, 1H), 9.06 (s, 1H), 8.67 (d, J = 2.0 Hz, 1H), 7.84 (dd, J1 = 2.8 Hz, J2 = 8.8 Hz, 1H), 7.64 (t, J = 8.0 Hz, 1H), 7.35 (d, J = 6.8 Hz, 1H), 7.23 (d, J = 8.4 Hz, 2H), 7.15 (d, J = 8.4 Hz, 2H), 6.91 (d, J = 8.4 Hz, 1H), 6.58 (d, J = 8.8 Hz, 1H), 3.34 (s, 3H), 1.90-1.69 (m, 5H), 1.42- 1.22 (m, 6H). LC-MS: m/z 403.2 (M + H)+. 646 138 XII.168 [01266] 1H NMR (400 MHz, DMSO-d6) δ 13.20- 12.40 (bs, 1H), 8.32 (s, 1H), 7.60 (t, J = 8.0 Hz, 1H), 7.33-7.28 (m, 2H), 7.05-7.00 (m, 4H), 6.78 (d, J = 2.4 Hz, 1H), 6.71- 6.67 (m, 2H), 4.75-4.68 (m, 2H), 3.20 (s, 3H), 2.13 (s, 3H). LC-MS: m/z 432.2 (M + H)+. 647 139 XII.169 [01267] 1H NMR (400 MHz, DMSO-d6) δ 8.42 (s, 1H), 7.66-7.60 (m, 2H), 7.35 (d, J = 6.4 Hz, 1H), 7.19 (d, J = 8.0 Hz, 2H), 7.05 (d, J = 2.4 Hz, 1H), 6.97-6.85 (m, 4H), 3.25 (s, 3H), 2.21 (s, 3H). LC- MS: m/z 418.05 (M + H)+ 648 140 XII.170 [01268] 1H NMR (400 MHz, DMSO-d6) δ 9.43 (s, 1H), 7.91 (d, J = 9.2 Hz, 2H), 7.74-7.70 (m, 1H), 7.46-7.43 (m, 3H), 7.17 (d, J = 8.8 Hz, 2H), 7.05 (d, J = 8.0 Hz, 1H), 6.78 (d, J = 8.8 Hz, 2H), 3.28 (s, 3H). LC-MS: m/z 388.05 (M + H)+. 649 141 XII.171 [01269] 1H NMR (400 MHz, DMSO-d6) δ 12.80 (bs, 1H), 10.21 (s, 1H), 8.40 (s, 1H), 8.32 (s, 1H), 7.92 (d, J = 8.4 Hz, 1H), 7.63 (d, J = 7.6 Hz, 1H), 7.45- 7.39 (m, 2H), 7.14 (d, J = 8.4 Hz, 2H), 7.05 (d, J = 8.4 Hz, 2H), 6.88 (d, J = 7.2 Hz, 2H), 2.36 (s, 3H), 1.79-1.68 (m, 5H), 1.39-1.23 (m, 6H). LC- MS: m/z 429.2 (M + H)+. 650 142 XII.172 [01270] 1H NMR (400 MHz, DMSO-d6) δ 12.90 (s, 1H), 8.80 (s, 1H), 7.53- 7.50 (m, 4H), 7.27 (d, J = 2.0 Hz, 1H), 7.18 (s, 1H), 7.13-7.11 (m, 1H), 7.01 (d, J = 8.4 Hz, 2H), 6.92 (d, J = 8.8 Hz, 1H), 3.75 (s, 3H), 2.03 (s, 3H), 1.81-1.71 (m, 12H). LC- MS: m/z 506.3 (M + 2H)+. 651 143 XV.50 [01271] 1H NMR (400 MHz, DMSO-d6) δ 13.0 (s, 1H), 10.1 (s, 1H), 8.39 (s, 1H), 8.04 (d, J = 8.0 Hz, 1H), 7.82 (d, J = 1.6 Hz, 1H), 7.72-7.69 (m, 1H), 6.63 (d, J = 7.6 Hz, 1H), 7.55 (s, 1H), 7.46-7.44 (m, 1H), 7.16-7.11 (m, 3H), 7.07 (d, J = 8.8 Hz, 2H), 2.52-2.46 (m, 1H), 2.29 (S, 3H), 1.80-1.68 (m, 5H), 1.40-1.17 (m, 5H), LC-MS: m/z 427.2 (M + H)+. 652 144 XII.173 [01272] 1H NMR (400 MHz, DMSO-d6) δ 8.62 (s, 1H), 8.49 (s, 1H), 7.73- 7.69 (m, 1H), 7.42 (d, J = 7.6 Hz, 1H), 7.36 (d, J = 8.4 Hz, 2H), 7.30 (d, J = 8.4 Hz, 2H), 7.22-7.09 (m, 1H) 6.76 (s, 1H), 3.42 (s, 3H), 2.25 (s, 3H), 1.85-1.70 (m, 5H), 1.45- 1.23 (m, 6H). LC-MS: m/z 417.2 (M + H)+. 654 145 XII.174 [01273] 1H NMR (400 MHz, DMSO-d6) δ 12.90 (s, 1H), 8.76 (s, 1H), 8.52 (d, J = 2.4 Hz, 1H), 7.71- 7.68 (m, 1H), 7.51 (d, J = 9.2 Hz, 1H), 7.23-7.12 (m, 4H), 6.87 (d, J = 9.2 Hz, 1H), 6.58 (d, J = 8.8 Hz, 1H), 3.74 (s, 3H), 3.29 (s, 3H), 2.49-2.47 (m, 1H), 1.81-1.79 (m, 5H), 1.39-1.37 (m, 5H). LC-MS: m/z 431.3 (M − H)+. 655 146 XII.175 [01274] 1H NMR (400 MHz, DMSO-d6) δ 7.70 (d, J = 2.4 Hz, 1H), 7.48-7.47 (m, 2H), 7.37 (dd, J1 = 6.8 Hz, J2 = 7.6 Hz, 1H), 7.27-7.13 (m, 5H), 7.05- 7.03 (m, 1H), 6.70 (d, J = 9.2 Hz, 1H), 3.38 (s, 3H), 2.48-2.47 (m, 1H), 1.79-1.66 (m, 5H), 1.42- 1.10 (m, 6H). LC-MS: m/z 402.5 (M + H)+. 656 147 XII.176 [01275] 1H NMR (400 MHz, DMSO-d6) δ 8.02-7.60 (m, 2H), 7.14 (d, J = 8.4 Hz, 4H), 6.97 (d, J = 8.4 Hz, 2H), 6.80 (d, J = 2.4 Hz, 1H), 6.76-6.74 (m, 1H), 6.40-6.30 (m, 1H), 3.22 (d, J = 8.8 Hz, 3H), 2.40 (s, 3H), 2.14 (s, 3H), 1.89-1.72 (m, 5H), 1.42- 1.31 (m, 6H). LC-MS: m/z 509.2 (M + H)+. 659 148 XII.177 [01276] 1H NMR (400 MHz, DMSO-d6) δ 8.37 (bs, 1H), 7.65 (bs, 1H), 7.55 (t, J = 8.0 Hz, 1H), 7.43 (d, J = 1.6 Hz, 1H), 7.35 (d, J = 8.0 Hz, 2H), 7.30- 7.25 (m, 2H), 6.75 (d, J = 7.6 Hz, 1H), 6.19 (d, J = 8.8 Hz, 1H), 3.29 (s, 3H), 2.45-2.41 (m, 1H), 1.84-1.69 (m, 5H), 1.45- 1.32 (m, 5H). LC-MS: m/z 437.2 (M + H)+. 660 149 XII.178 [01277] 1H NMR (400 MHz, DMSO-d6) δ 10.75 (bs, 1H), 8.03 (s, 1H), 7.66 (t, J = 8.0 Hz, 1H), 7.38-7.32 (m, 3H), 7.23-7.17 (m, 3H), 7.09 (d, J = 7.6 Hz, 1H), 6.72 (s, 1H), 2.45- 2.41 (m, 1H), 1.79-1.67 (m, 5H), 1.43-1.30 (m, 5H). LC-MS: m/z 490.1 (M + H)+. 661 150 XII.179 [01278] 1H NMR (400 MHz, DMSO-d6) δ 8.96 (s, 1H), 8.25 (s, 1H), 7.49 (s, 1H), 7.37-7.34 (m, 2H), 7.16 (d, J = 8.0 Hz, 2H), 7.06 (d, J = 8.0 Hz, 2H), 6.75 (d, J = 8.4 Hz, 1H), 6.65 (s, 1H), 3.69 (s, 3H), 2.46-2.39 (m, 1H), 1.79- 1.68 (m, 5H), 1.39-1.23 (m, 5H). LC-MS: m/z 486.2 (M + H)+. 662 151 XII.180 [01279] 1H NMR (400 MHz, DMSO-d6) δ 12.90 (s, 1H), 8.60 (s, 1H), 8.36 (s, 1H), 7.69 (d, J = 2.0 Hz, 1H), 7.44-7.36 (m, 3H), 7.13 (d, J = 8.4 Hz, 2H), 7.04 (d, J = 8.4 Hz, 2H), 6.98 (s, 1H), 6.66 (d, J = 14.0 Hz, 2H), 1.77- 1.75 (m, 6H), 1.38-1.22 (m, 5H). LC-MS: m/z 469.1 (M + H)+. 663 152 XII.181 [01280] 1H NMR (400 MHz, DMSO-d6) δ 8.08 (s, 1H), 7.62 (t, J = 9.6 Hz, 1H), 7.32-7.24 (m, 3H), 7.17 (d, J = 8.0 Hz, 2H), 6.62 (d, J = 7.2 Hz, 1H), 6.06 (s, 1H), 3.34 (s, 3H), 1.81-1.69 (m, 7H), 1.42- 1.23 (m, 5H), 0.84-0.82 (bs, 2H), 0.44-0.43 (m, 2H). LC-MS: m/z 443.2 (M + H)+. 664 153 XV.51 [01281] 1H NMR (400 MHz, DMSO-d6) δ 13.20 (s, 1H), 10.14 (s, 1H), 9.90 (s, 1H), 7.93 (d, J = 6.8 Hz, 1H), 7.78 (s, 1H), 7.66-7.60 (m, 3H), 7.50- 7.40 (m, 3H), 7.30 (d, J = 4.0 Hz, 1H), 7.18 (d, J = 8.4 Hz, 2H), 6.83 (t, J = 7.2 Hz, 1H), 1.78-1.68 (m, 5H), 1.44-1.23 (m, 6H). LC-MS: m/z 415.2 (M + H)+. 665 154 XII.182 [01282] 1H NMR (400 MHz, DMSO-d6) δ 13.72 (bs, 1H), 10.60 (s, 1H), 9.95 (s, 1H), 8.42 (d, J = 2.8 Hz, 1H), 8.29-8.27 (m, 1H), 8.20 (s, 1H), 8.07 ((d, J = 8.4 Hz, 1H), 7.62 (d, J = 7.2 Hz, 1H), 7.50- 7.46 (m, 2H), 7.38 (s, 1H), 7.24 (d, J = 8.4 Hz, 1H), 6.93-6.90 (m, 1H), 2.49-2.47 (m, 1H), 1.81- 1.69 (m, 5H), 1.43-1.23 (m, 5H). LC-MS: m/z 450.1 (M + H)+. 666 155 XII.183 [01283] 1H NMR (400 MHz, DMSO-d6) δ 13.19 (s, 1H), 9.97 (s, 1H), 9.75 (s, 1H), 7.93 (dd, J1 = 0.8 Hz, J2 = 7.6 Hz, 1H), 7.81 (s, 1H), 7.640 (d, J = 6.0 Hz, 1H), 7.52-7.38 (m, 5H), 7.31 (d, J = 8.4 Hz, 1H), 7.24-7.22 (m, 1H), 6.86- 6.82 (m, 1H), 2.49-2.43 (m, 1H), 1.81-1.68 (m, 5H) 1.46-1.22 (m, 5H). LC-MS: m/z 449.05 (M + H)+. 669 156 XII.184 [01284] 1H NMR (400 MHz, DMSO-d6) δ 13.25 (bs, 1H), 9.91 (s, 1H), 9.29 (bs, 1H), 7.70 (s, 1H), 7.53 (d, J = 8 Hz, 1H), 7.47-7.32 (m, 6H), 7.23 (d, J = 8 Hz, 1H), 7.12 (dd, J1 = 2.8 Hz, J2 = 8.8 Hz, 1H), 3.74 (s, 3H), 2.45-2.41 (m, 1H), 1.81- 1.68 (m, 5H), 1.46-1.31 (m, 5H). LC-MS: m/z 479.2 (M + H)+. 671 157 XII.185 [01285] 1H NMR (400 MHz, DMSO-d6) δ 13.40 (s, 1H), 9.61 (s, 1H), 8.23 (d, J = 2.0 Hz, 1H), 7.60 (dd, J1 = 2.4 Hz, J2 = 9.2 Hz, 1H), 7.44 (s, 1H), 7.30 (s, 2H), 7.21 (d, J = 6.5 Hz, 1H), 7.04 (d, J = 8.8 Hz, 1H), 6.60-6.50 (m, 2H), 6.33 (dd, J1 = 2.8 Hz, J2 = 8.2 Hz, 1H), 3.19 (s, 3H), 2.36 (d, J = 4.8 Hz, 3H), 2.07 (s, 3H), 1.84-1.68 (m, 5H), 1.44- 1.16 (m, 6H). LC-MS: m/z 542.2 (M + H)+. 672 158 XII.186 [01286] 1H NMR (400 MHz, DMSO-d6) δ 9.88 (s, 1H), 7.63 (dd, J1 = 2.8 Hz, J2 = 6.8 Hz, 2H), 7.47 (d, J = 8 Hz, 1H), 7.41-7.33 (m, 3H), 7.29-7.21 (m, 3H), 6.97 (d, J = 7.6 Hz, 1H), 3.80-3.75 (m, 1H), 2.45-2.41 (m, 1H), 1.81- 1.68 (m, 5H), 1.46-1.32 (m, 5H), 0.74-0.73 (m, 2H), 0.64-0.60 (m, 2H). LC-MS: m/z 505.2 (M + H)+. 673 159 XII.187 [01287] 1H NMR (400 MHz, DMSO-d6) δ 8.75-9.00 (bs, 1H), 7.97 (s, 1H), 7.55 (d, J = 2.4 Hz, 1H), 7.26 (d, J = 8.4 Hz, 2H), 7.20 (d, J = 8.4 Hz, 2H), 7.00 (dd, J1 = 2.4 Hz, J2 = 9.2 Hz, 1H), 6.49 (s, 1H), 6.43 (d, J = 9.2 Hz, 1H), 3.78-3.71 (m, 1H), 3.35 (s, 3H), 2.45-2.41 (m, 1H), 1.97 (s, 3H), 1.85-1.69 (m, 5H), 1.46- 1.32 (m, 5H), 0.75-0.70 (m, 2H), 0.65-0.58 (m, 2H). LC-MS: m/z 472.25 (M + H)+. 675 160 XII.188 [01288] 1H NMR (400 MHz, DMSO-d6) δ 8.74 (s, 1H), 7.80 (s, 1H), 7.53 (s, 1H), 7.33-7.09 (m, 5H), 6.05 (s, 1H), 6.57 (d, J = 8.4 Hz, 1H), 3.63 (s, 3H), 2.49-2.47 (m, 1H), 1.80-1.67 (m, 5H), 1.40- 1.33 (m, 5H). LC-MS: m/z 518.1 (M + H)+. 676 161 XII.189 [01289] 1H NMR (400 MHz, DMSO-d6) δ 12.92 (s, 1H), 8.58 (s, 1H), 8.02 (s, 1H), 7.65 (s, 1H), 7.45- 7.29 (m, 5H), 7.17-7.15 (m, 1H), 6.80 (s, 1H), 6.67 (s, 2H), 2.60-2.40 (m, 1H), 1.79-1.67 (m, 5H), 1.36-1.22 (m, 5H). LC-MS: m/z 489.2 (M + H)+. 677 162 XII.190 [01290] 1H NMR (400 MHz, DMSO-d6) δ 13.60 (s, 1H), 10.48 (s, 1H), 8.34- 8.33 (m, 1H), 8.22 (dd, J1 = 2.0 Hz, J2 = 8.0 Hz, 1H), 7.54 (s, 1H), 7.47 (s, 1H), 7.29-7.20 (m, 2H), 7.15-7.09 (m, 3H), 6.83 (dd, J1 = 4.8 Hz, J2 = 7.6 Hz, 1H), 6.65-6.63 (m, 1H), 2.49-2.45 (m, 1H), 1.77-1.67 (m, 5H), 1.42- 1.18 (m, 5H). LC-MS: m/z 422.1 (M + H)+. 678 163 XII.191 [01291] 1H NMR (400 MHz, DMSO-d6) δ 13.2 (s, 1H), 9.70 (s, 1H), 8.18 (d, J = 2.4 Hz, 1H), 7.57 (dd, J1 = 2.4 Hz, J2 = 8.8 Hz, 1H), 7.17-7.12 (m, 3H), 6.99 (d, J = 8.8 Hz, 2H), 6.91 (d, J = 2.4 Hz, 1H), 6.78 (dd, J1 = 2.8 Hz, J2 = 8.4 Hz, 1H), 6.60 (d, J = 8.8 Hz, 1H), 4.40 (bs, 4H), 3.90-3.80 (m, 1H), 3.24 (s, 3H), 2.45-2.42 (m, 1H), 2.10 (s, 3H), 1.79-1.77 (m, 5H), 1.39- 1.34 (m, 5H). LC-MS: m/z 523.3 (M + H)+ 679 164 XII.191 [01292] 1H NMR (400 MHz, DMSO-d6) δ 13.19 (s, 1H), 9.61 (s, 1H), 8.19 (s, 1H), 7.58 (dd, J1 = 1.6 Hz, J2 = 8.8 Hz, 1H), 7.47 (s, 1H), 7.17-7.12 (m, 3H), 7.03-6.98 (m, 3H), 6.91 (s, 1H), 6.78 (dd, J1 = 2.2 Hz, J2 = 8.8 Hz, 1H), 6.62 (d, J = 8.8 Hz, 1H), 4.39- 3.98 (m, 4H), 3.23 (s, 3H), 2.49-2.43 (m, 1H), 2.10 (s, 3H), 1.79-1.68 (m, 6H), 1.42-1.30 (m, 5H). LC-MS: m/z 541.3 (M + H)+ 680 165 XII.192 [01293] 1H NMR (400 MHz, DMSO-d6) δ 8.86 (s, 1H), 7.62-7.56 (m, 2H), 7.33-7.22 (m, 3H), 7.11- 7.02 (m, 2H), 6.96 (d, J = 2.0 Hz, 1H), 6.88-6.83 (m, 1H), 6.41 (d, J = 8.4 Hz, 1H), 2.47-2.42 (m, 1H), 2.09 (s, 3H), 1.81- 1.66 (m, 5H), 1.42-1.22 (m, 5H). LC-MS: m/z 436.2 (M + H)+ 681 166 XII.193 [01294] 1H NMR (400 MHz, DMSO-d6) δ 8.25 (s, 1H), 7.56-7.54 (m, 1H), 7.41 (s, 1H), 7.28-7.23 (m, 3H), 7.15-7.12 (m, 1H), 6.57-6.47 (m, 2H), 6.30 (d, J = 5.6 Hz, 1H), 3.17 (s, 3H), 2.04 (s, 3H), 1.86-1.66 (m, 5H), 1.44- 1.15 (m, 6H). LC-MS: m/z 450.2 (M + H)+ 682 167 XII.194 [01295] 1H NMR (400 MHz, DMSO-d6) δ 10.4 (s, 1H), 7.62-7.55 (m, 2H), 7.32-7.26 (m, 4H), 7.16- 6.95 (m, 5H), 6.61 (d, J = 7.6 Hz, 1H), 2.44-2.32 (m, 1H), 1.84-1.67 (m, 5H), 1.38-1.19 (m, 5H). LC-MS: m/z 422.0 (M + H)+

[0633] The below compounds were prepared by a procedure similar to Intermediate-XV using appropriate reactants and reagents and in presence of suitable solvents and appropriate reaction conditions.

TABLE-US-00033 Com- pound CP No Reactant Structure Analytical data  72 277 Compound 24 [01296] LC-MS: m/z 466.1 (M + H).sup.+  94 278 Int-XI [01297] .sup.1H NMR (400 MHz, DMSO-d6) δ 14.55 (bs, 1H), 10.20 (bs, 1H), 8.72 (bs, 1H), 7.68 (d, J = 8.8 Hz, 2H), 7.49 (s, 1H), 7.32 (d, J = 2.0 Hz, 1H), 7.20-7.15 (m, 2H), 7.02 (d, J = 8.8 Hz, 2H), 2.04 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 448.1 (M + H).sup.+ 111 279 Compound 31 [01298] .sup.1H NMR (400 MHz, DMSO-d6) δ 9.91 (s, 1H), 7.99 (s, 1H), 7.68 (dd, J.sub.1 = 1.6 Hz, J.sub.2 = 8.0 Hz, 1H), 7.42 (s, 1H), 7.37 (s, 1H), 7.31 (d, J = 2.0 Hz, 1H), 7.29-7.24 (m, 1H), 7.19-7.12 (m, 2H), 7.08-7.02 (m, 5H), 6.68 (t, J = 7.2 Hz, 1H), 2.04 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 472.2 (M + H).sup.+ 112 280 Compound 279 [01299] .sup.1H NMR (400 MHz, DMSO-d6) δ 8.45 (s, 1H), 8.14-8.12 (m, 2H), 7.74-7.70 (m, 1H), 7.51 (t, J = 8.4 Hz, 1H), 7.43-7.38 (m, 4H), 7.33-7.29 (m, 1H), 7.01 (d, J = 8.8 Hz, 2H), 6.98 (d, J = 8.4 Hz, 1H), 2.06 (s, 3H), 1.87 (s, 6H), 1.73 (s, 6H). LC-MS: m/z 482.1 (M + H).sup.+ 120 281 Compound 31 [01300] .sup.1H NMR (400 MHz, DMSO-d6) δ 9.61 (s, 1H), 8.48 (m, 1H), 7.61 (dd, J.sub.1 = 1.6 Hz, J.sub.2 = 8.0 Hz, 1H), 7.40 (s, 1H), 7.31 (d, J = 2.4 Hz, 1H), 7.26 (t, J = 8.4 Hz, 1H), 7.19-7.01 (m, 7H), 6.74-6.70 (m, 1H), 3.29-3.24 (m, 2H), 2.04 (s, 3H), 1.82 (s, 6H), 1.72 (s, 6H), 1.12 (t, J = 7.2 Hz, 3H). LC-MS: m/z 500.2 (M + H).sup.+ 123 282 Compound 31 [01301] .sup.1H NMR (400 MHz, DMSO-d6) δ 7.41 (s, 1H), 7.29 (d, J = 2.0 Hz, 1H), 7.27 (s, 1H), 7.24-7.21 (m, 1H), 7.18-7.13 (m, 2H), 7.10-7.03 (m, 2H), 6.99 (s, 4H), 6.83 (t, J = 7.2 Hz, 1H), 2.91 (s, 6H), 2.04 (s, 3H), 1.82 (s, 6H), 1.71 (s, 6H). LC-MS: m/z 500.4 (M + H).sup.+ 164 283 Compound 31 [01302] .sup.1H NMR (400 MHz, DMSO-d6) δ 9.62 (s, 1H), 8.45 (s, 1H), 7.59 (dd, J.sub.1 = 1.6 Hz, J.sub.2 = 8.0 Hz, 1H), 7.40 (s, 1H), 7.31 (d, J = 2.0 Hz, 1H), 7.26 (t, J = 6.8 Hz, 1H), 7.20-7.02 (m, 7H), 6.72 (t, J = 7.6 Hz, 1H), 2.77 (d, J = 5.2 Hz, 3H), 2.04 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H). LC- MS: m/z 485.2 (M + H).sup.+ 208 284 Compound 92 [01303] .sup.1H NMR (400 MHz, DMSO-d6) δ 9.0 (s, 1H), 7.6 (d, J = 7.3 Hz, 1H), 7.5 (d, J = 8.9 Hz, 2H), 7.29 (d, J = 2.9 Hz, 1H), 7.26 (s, 1H), 7.15 (m, 1H), 7.07-7.01 (m, 3H), 6.79 (t, J = 8.3 Hz, 2H), 2.98 (s, 6H), 2.04 (s, 3H), 1.82 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 501.3 (M + H).sup.+ 209 285 Compound 60 [01304] .sup.1H NMR (400 MHz, DMSO-d6) δ 8.23 (s, 1H), 8.15 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 7.6 Hz, 1H), 7.55 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 7.6 Hz, 1H), 7.45 (d, J = 8.8 Hz, 2H), 7.29 (s, 2H), 7.16 (dd, J.sub.1 = 2.8 Hz, J.sub.2 = 8.8 Hz, 1H), 7.07 (d, J = 8.4 Hz, 1H), 7.01 (d, J = 8.8 Hz, 2H), 6.78 (dd, J.sub.1 = 4.8 Hz, J.sub.2 = 7.2 Hz, 1H), 2.97 (s, 6H), 2.04 (s, 3H), 1.82 (s, 6H), 1.72 (s, 6H). LC- MS: m/z 501.3 (M + H).sup.+ 605 168 Compound 279 [01305] 1H NMR (400 MHz, DMSO-d6) δ 9.35 (s, 1H), 8.08 (s, 1H), 7.51 (bs, 1H), 7.44 (d, J = 8.4 Hz, 2H), 7.30-7.27 (m, 2H), 7.12-7.00 (m, 5H), 6.77 (d, J = 8.8 Hz, 2H), 3.76 (s, 3H), 3.25 (s, 3H). LC- MS: m/z 416.10 (M + H)+. 606 169 Compound 279 [01306] 1H NMR (400 MHz, DMSO-d6) δ 9.06 (s, 1H), 8.49-8.52 (m, 1H), 7.42 (d, J = 8.8 Hz, 2H), 7.28 (d, J = 8.8 Hz, 1H), 7.17 (d, J = 2.4 Hz, 1H), 7.09-7.03 (m, 4H), 7.01-6.96 (m, 1H), 6.74 (d, J = 8.8 Hz, 2H), 3.75 (s, 3H), 3.23 (s, 3H), 2.74 (d, J = 4.8 Hz, 3H). LC-MS: m/z 430.2 (M + H)+. 607 170 Compound 279 [01307] 1H NMR (400 MHz, DMSO-d6) δ 7.42 (d, J = 8.8 Hz, 3H), 7.22 (d, J = 8.8 Hz, 1H), 7.00 (d, J = 8.4 Hz, 2H), 6.97-6.94 (m, 1H), 6.89 (d, J = 8.8 Hz, 2H), 6.81 (d, J = 3.2 Hz, 1H), 6.72 (d, J = 8.8 Hz, 2H), 3.75 (s, 3H), 3.22 (s, 3H), 2.90 (s, 3H), 2.81 (s, 3H). LC-MS: m/z 444.2 (M + H)+. 653 171 XI.53 [01308] 1H NMR (400 MHz, DMSO-d6) δ 9.00 (s, 1H), 8.43 (d, J = 4.8 Hz, 1H), 7.83 (d, J = 8.8 Hz, 1H), 7.22-7.14 (m, 3H), 6.97 (d, J = 8.4 Hz, 2H), 6.87 (d, J = 2.0 Hz, 1H), 6.77-6.75 (m, 2H), 6.56-6.51 (m, 1H), 3.23 (s, 3H), 2.73 (d, J = 4.8 Hz, 3H), 2.45 (d, J = 5.2 Hz, 3H), 2.14 (s, 3H), 1.79-1.68 (m, 5H), 1.44-1.34 (m, 6H). LC-MS: m/z 522.2 (M + H)+

[0634] The below compounds were prepared by a procedure similar to Intermediate-XIV using appropriate reactants and reagents and in presence of suitable solvents and appropriate reaction conditions.

TABLE-US-00034 Com- pound CP No Reactant Structure Analytical data 109 286 XV.4 [01309] .sup.1H NMR (400 MHz, DMSO-d6) δ 9.86 (s, 1H), 7.50 (d, J = 8.8 Hz, 2H), 7.41 (s, 1H), 7.31 (s, 1H), 7.18 (m, 1H), 7.11 (s, 1H), 6.98 (d, J = 4.0 Hz, 2H), 3.74 (m, 1H), 2.95 (t, J = 6.9 Hz, 2H), 2.08 (m, 4H), 1.90 (m, 7H), 1.68 (m, 7H), 1.56-1.48 (m, 1H). LC- MS: m/z 450.2 (M + H).sup.+ 230 287 XV.10 [01310] .sup.1H NMR (400 MHz, DMSO-d6) δ 9.88 (s, 1H), 7.51 (d, J = 8.8 Hz, 2H), 7.38 (s, 1H), 7.30 (d, J = 2.0 Hz, 1H), 7.16-7.14 (m, 1H), 7.1 (d, J = 8.8 Hz, 1H), 6.99 (d, J = 8.8 Hz, 2H), 2.04 (s, 3H), 1.82 (s, 6H), 1.72 (s, 6H), 1.17-1.15 (m, 2H), 0.87-0.84 (m, 2H). LC-MS: m/z 436.2 (M + H).sup.+ 152 288 Compound 77 [01311] .sup.1H NMR (400 MHz, DMSO-d6) δ 13.21 (bs, 1H), 10.60 (bs, 1H), 8.48 (d, J = 8.0 Hz, 1H), 8.08 (d, J = 2.8 Hz, 1H), 7.94 (dd, J.sub.1 = 1.6 Hz, J.sub.2 = 8.0 Hz, 1H), 7.51-7.44 (m, 3H), 7.31 (d, J = 2.0 Hz, 1H), 7.16 (dd, J.sub.1 = 1.6 Hz, J.sub.2 = 8.0 Hz, 1H), 6.98 (t, J = 8.4 Hz, 2H), 6.87 (t, J = 8.4 Hz, 1H), 2.04 (s, 3H), 1.82 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 474.3 (M + H).sup.+ 155 289 Compound 288 [01312] .sup.1H NMR (400 MHz, DMSO-d6) δ 8.36 (d, J = 2.4 Hz, 1H), 8.26 (dd, J.sub.1 = 1.2 Hz, J.sub.2 = 8.0 Hz, 1H), 8.07 (s, 1H), 7.88-7.84 (m, 1H), 7.75-7.70 (m, 2H), 7.56 (d, J = 10 Hz, 1H), 7.51-7.47 (m, 1H), 7.43 (d, J = 2.0 Hz, 1H), 7.32-7.26 (m, 2H), 2.06 (s, 3H), 1.87 (s, 6H), 1.74 (s, 6H). LC-MS: m/z 456.3 (M + H).sup.+ 153 290 Compound 75 [01313] .sup.1H NMR (400 MHz, DMSO-d6) δ 13.21 (bs, 1H), 10.46 (bs, 1H), 8.45 (s, 1H), 8.14 (d, J = 8.0 Hz, 1H), 8.11 (d, J = 8.8 Hz, 1H), 8.04 (s, 1H), 7.94 (dd, J.sub.1 = 1.6 Hz, J.sub.2 = 8.0 Hz, 1H), 7.78 (d, J = 8.4 Hz, 1H), 7.47 (t, J = 8.4 Hz, 1H), 7.35 (d, J = 2.4 Hz, 1H), 7.26 (dd, J.sub.1 = 2.4 Hz, J.sub.2 = 8.8 Hz, 1H), 6.87 (t, J = 7.2 Hz, 1H), 2.05 (s, 3H), 1.85 (s, 6H), 1.73 (s, 6H). LC-MS: m/z 475.5 (M + H).sup.+ 154 291 Compound 74 [01314] .sup.1H NMR (400 MHz, DMSO-d6) δ 13.43 (bs, 1H), 11.21 (bs, 1H), 8.82 (d, J = 7.6 Hz, 1H), 8.44 (s, 2H), 8.0 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 8.4 Hz, 1H), 7.60-7.54 (m, 2H), 7.32 (d, J = 2.0 Hz, 1H), 7.16 (dd, J.sub.1 = 2.4 Hz, J.sub.2 = 8.8 Hz, 1H), 7.02-6.95 (m, 2H), 2.04 (s, 3H), 1.82-1.81 (bs, 6H), 1.72 (s, 6H). LC-MS: m/z 475.2 (M + H).sup.+ 175 292 VI.19 [01315] .sup.1H NMR (400 MHz, DMSO-d6) δ 13.65 (bs, 1H), 10.95 (bs, 1H), 8.42 (s, 2H), 8.29 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 8.0 Hz, 1H), 8.10 (d, J = 3.2 Hz, 1H), 7.54 (m, 2H), 7.32 (d, J = 2.0 Hz, 1H), 7.16 (dd, J.sub.1 = 2.0 Hz, J.sub.2 = 8.4 Hz, 1H), 7.02 (d, J = 8.4 Hz, 1H), 6.92 (dd, J.sub.1 = 5.2 Hz, J.sub.2 = 8.0 Hz, 1H), 2.08 (s, 3H), 1.82 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 475.2 (M + H).sup.+ 540 172 IX.5 [01316] 1H NMR (400 MHz, DMSO-d6): δ 13.38 (s, 1H), 10.75 (s, 1H), 8.36 (d, J = 8.4 Hz, 1H), 8.26 (d, J = 1.6 Hz, 1H), 8.05 (d, J = 1.2 Hz, 1H), 7.97 (dd, J.sub.1 = 1.6 Hz & J.sub.2 = 8.0 Hz, 1H), 7.55-7.51 (m, 1H), 7.49 (d, J = 2.4 Hz, 1H), 7.38-7.35 (m, 1H), 7.22 (d, J = 8.8 Hz, 1H), 6.97 (t, J = 8 Hz, 1H), 2.06 (s, 3H), 1.88 (s, 6H), 1.74 (s, 6H), LC-MS: m/z 476.2 (M + H)+ 559 173 XII.98 [01317] 1H NMR (400 MHz, DMSO-d6): δ 13.38 (bs, 1H), 11.05 (bs, 1H), 8.36 (d, J = 8.8 Hz, 1H), 8.24 (s, 1H), 8.02 (s, 1H), 7.97 (d, J = 6.8 Hz, 1H), 7.50 (t, J = 7.6 Hz, 1H), 7.41 (d, J = 1.6 Hz, 1H), 7.24-7.17 (m, 2H), 6.95 (t, J = 7.2 Hz, 1H), 2.58-2.52 (m, 1H), 1.81-1.68 (m, 5H), 1.42-1.31 (m, 5H). LC-MS: m/z 424.2 (M + H)+.

Synthesis of 2-((4-(4-((3r,5r,7r)-adamantan-1-yl)-2-chlorophenyl)amino)phenyl)carbamoyl) benzoic acid (Compound-293) (CP-119)

[0635] ##STR01318##

[0636] Step (i): A solution of Intermediate-XI (0.05 g, 0.16 mmol, 1 eq.) and phthalic anhydride (0.024 g, 0.16 mmol, 1 eq.) in DCM was stirred at RT for 2 h. The precipitate obtained was filtered and dried in vacuo to afford title product as pale-yellow solid (0.01 g, 12.50%).

[0637] .sup.1H NMR (400 MHz, DMSO-d6) δ12.98 (s, 1H), 10.17 (s, 1H), 7.86 (d, J=7.8 Hz, 1H), 7.63 (d, J=7.3 Hz, 1H), 7.57-7.52 (m, 4H), 7.41 (s, 1H), 7.31 (d, J=1.6 Hz, 1H), 7.17-7.12 (m, 2H), 7.04 (d, J=8.8 Hz, 2H), 2.05 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 501.1 (M+H).sup.+2

[0638] The below compounds were prepared by a procedure similar to Compound 293 using appropriate reactants and reagents and in presence of suitable solvents and appropriate reaction conditions.

TABLE-US-00035 Compound CP No Reactant Structure Analytical data  90 294 Int-I.1 [01319] .sup.1H NMR (400 MHz, DMSO-d6) δ 11.80 (bs, 1H), 9.75 (s, 1H), 7.47 (d, J = 8.8 Hz, 2H), 7.23 (d, J = 8.8 Hz, 2H), 3.12-3.08 (m, 1H), 2.93-2.91 (m, 1H), 2.00-1.92 (m, 4H), 1.91-1.75 (m, 16H), 1.72-1.54 (m, 1H). LC-MS: m/z 368.1 (M + H).sup.+  96 295 Int-XI [01320] .sup.1H NMR (400 MHz, DMSO-d6) δ 11.9 (bs, 1H), 9.71 (bs, 1H), 7.43 (d, J = 8.8 Hz, 2H), 7.33 (s, 1H), 7.30 (d, J = 2.5 Hz, 1H), 7.16-7.14 (m, 1H), 7.08 (m, 1H), 6.97 (d, J = 8.8 Hz, 2H), 3.12-3.08 (m, 1H), 2.94-2.90 (m, 1H), 2.04 (s, 4H), 1.99-1.82 (m, 10H), 1.71 (m, 7H). LC-MS: m/z 493.3 (M + H).sup.+ 105 296 Int-I.1 [01321] .sup.1H NMR (400 MHz, DMSO-d6) δ 7.52 (d, J = 8.8 Hz, 2H), 7.27 (d, J = 8.4 Hz, 2H), 2.72 (t, J = 7.2 Hz, 2H), 2.67-2.63 (m, 2H), 2.05 (s, 3H), 1.79 (d, J = 7.6 Hz, 8H), 1.69 (s, 6H). LC-MS: m/z 366.1 (M + H).sup.+ 110 297 Int-XI [01322] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.9 (bs, 1H), 10.06 (s, 1H), 7.47 (d, J = 8.8 Hz, 2H), 7.42 (s, 1H), 7.30 (d, J = 2.0 Hz, 1H), 7.17-7.10 (m, 2H), 6.98 (d, J = 8.8 Hz, 2H), 2.76 (t, J = 7.6 Hz, 2H), 2.74-2.62 (m, 2H), 2.03 (s, 3H), 1.90-1.86 (m, 2H), 1.81-1.80 (bs, 6H), 1.71 (s, 6H). LC-MS: m/z 491.1 (M + H).sup.+ 132 298 XI.2 [01323] .sup.1H NMR (400 MHz, DMSO-d6) δ 11.83 (s, 1H), 9.74 (s, 1H), 7.54 (s, 1H), 7.5 (d, J = 8.8 Hz, 2H), 7.34 (s, 1H), 7.28-7.15 (m, 4H), 7.13 (s, 2H), 7.09 (d, J = 8.8 Hz, 2H), 3.13-3.09 (m, 1H), 2.96-2.90 (m, 1H), 2.25 (s, 3H), 2.04-1.77 (m, 4H). LC-MS: m/z 449.1 (M + H).sup.+ 133 299 XI.2 [01324] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.85 (bs, 1H), 10.15 (s, 1H), 7.62 (s, 1H), 7.55 (d, J = 8.8 Hz, 2H), 7.35 (d, J = 2.0 Hz, 1H), 7.29-7.11 (m, 8H), 2.80-2.76 (m, 2H), 2.65-2.63 (m, 2H), 2.26 (s, 3H), 1.94-1.88 (m, 2H). LC-MS: m/z 447.1 (M + H).sup.+ 176 300 Int-XI [01325] .sup.1H NMR (400 MHz, DMSO-d6) δ 13.05 (bs, 1H), 10.42 (bs, 1H), 7.46 (d, J = 8.8 Hz, 2H), 7.42 (s, 1H), 7.31 (d, J = 2.0 Hz, 1H), 7.16 (m, 1H), 7.12 (m, 1H), 6.98 (d, J = 8.8 Hz, 2H), 2.04 (s, 3H), 1.82 (s, 6H), 1.72 (s, 6H), 1.41 (s, 4H). LC-MS: m/z 465.3 (M + H).sup.+ 216 301 XI.1 [01326] .sup.1H NMR (400 MHz, DMSO-d6) δ 14.8 (bs, 1H), 8.04 (s, 1H), 7.46 (s, 1H), 7.41 (s, 1H), 7.30 (s, 2H), 7.19 (s, 1H), 6.82 (s, 1H), 2.06 (s, 3H), 1.86 (d, J = 2.4 Hz, 6H), 1.63 (s, 6H), 1.19 (d, J = 5.6 Hz, 2H), 1.10 (d, J = 5.6 Hz, 2H). LC-MS: m/z 533.2 (M + H).sup.+ 229 302 Compound 300 [01327] .sup.1H NMR (400 MHz, DMSO-d6) δ 10.56 (s, 1H), 7.82 (d, J = 4.4 Hz, 1H), 7.47-7.42 (m, 3H), 7.31 (d, J = 2.0 Hz, 1H), 7.19-7.16 (m, 1H), 7.11 (d, J = 8.4 Hz, 1H), 6.98 (d, J = 8.8 Hz, 2H), 2.62 (d, J = 4.4 Hz, 3H), 2.04 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H), 1.36-1.29 (m, 4H). LC-MS: m/z 478.3 (M + H).sup.+ 237 303 XI.7 [01328] .sup.1H NMR (400 MHz, DMSO-d6) δ 7.53 (s, 1H), 7.34 (d, J = 2.0 Hz, 1H), 7.30 (s, 1H), 7.25-7.22 (m, 2H), 7.11 (t, J = 7.6 Hz, 1H), 7.03 (d, J = 8.0 Hz, 1H), 6.50 (d, J = 8.0 Hz, 1H), 2.05 (s, 3H), 1.84 (s, 6H), 1.73 (s, 6H), 1.34-1.24 (m, 4H). LC-MS: m/z 465.2 (M + H).sup.+ 239 304 VI.37 [01329] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.4 (bs, 1H), 7.7 (s, 1H), 7.36 (s, 1H), 7.23 (s, 2H), 7.14 (d, J = 7.8 Hz, 2H), 6.95 (d, J = 8.3 Hz, 2H), 3.13 (s, 3H), 2.08 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H), 1.17 (m, 2H), 0.85 (m, 2H). LC-MS: m/z 479.2 (M + H).sup.+ 348 305 XI.30 [01330] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.85 (bs, 1H), 10.11 (bs, 1H), 7.91 (s, 1H), 7.85 (d, J = 8.0 Hz, 1H), 7.64 (t, J = 7.6 Hz, 1H), 7.57-7.52 (m, 4H), 7.19 (d, J = 8.8 Hz, 2H), 7.02-6.96 (m, 4H), 2.04 (s, 3H), 1.83 (s, 6H), 1.73 (s, 6H). LC- MS: m/z 465.2 (M − H).sup.+ 378 306 XI.29 [01331] .sup.1H NMR (400 MHz, DMSO-d6) δ 12.97 (s, 1H), 10.19 (s, 1H), 8.06 (s, 1H), 7.85 (d, J = 7.6 Hz, 1H), 7.63 (t, J = 7.2 Hz, 1H), 7.57-7.50 (m, 3H), 7.21 (d, J = 8.4 Hz, 2H), 7.13-7.10 (m, 2H), 7.04 (d, J = 8.4 Hz, 2H), 6.71 (d, J = 7.2 Hz, 1H), 2.04 (s, 3H), 1.83 (s, 6H), 1.72 (s, 6H). LC-MS: m/z 467.3 (M + H).sup.+

[0639] Experimental procedure and physiochemical characteristics of the compound CP-453

Intermediate

[0640] ##STR01332##

[0641] The above intermediate was prepared by a procedure similar to Intermediate-XII by using Intermediate-XI.16 (0.145 g, 0.43 mmol, 1 eq.) and methyl 2-bromo-5-isobutoxybenzoate (0.125 g, 0.43 mmol, 1 eq.) to afford title product as brown solid (0.05 g, 22%). .sup.1H NMR (400 MHz, DMSO-d.sub.6): δ 8.79 (s, 1H), 7.54-7.52 (m, 1H), 7.44-7.42 (m, 1H), 7.28-6.98 (m, 9H), 3.85 (s, 3H), 3.80 (d, J=2.4 Hz, 2H), 3.37 (s, 3H), 2.04 (s, 3H), 2.00-1.96 (m, 1H), 1.83 (s, 6H), 1.72 (s, 6H), 0.97 (d, J=6.4 Hz, 6H).

Final Compound

[0642] ##STR01333##

[0643] The above compound was prepared by a procedure similar to the one described in compound-24 by using appropriate reagents in the presence of suitable solvents at appropriate reaction conditions. The physiochemical characteristics of the compound also summarized.

[0644] .sup.1H NMR (400 MHz, DMSO-d.sub.6): δ 13.10 (s, 1H), 9.12 (s, 1H), 7.37 (d, J=2.0 Hz, 1H), 7.23 (d, J=8.4 Hz, 2H), 7.10 (d, J=9.2 Hz, 2H), 7.05 (dd, J.sub.1=2.8 Hz, J.sub.2=9.2 Hz, 2H), 6.97 (d, J=8.8 Hz, 2H), 6.89 (d, J=8.8 Hz, 2H), 3.68 (d, J=6.4 Hz, 2H), 3.21 (s, 3H), 2.04 (s, 3H), 2.01-1.98 (m, 1H), 1.83 (d, J=2.6 Hz, 6H), 1.72 (s, 6H), 0.97 (d, J=6.8 Hz, 6H). LC-MS: 525.3 (M+H).sup.+

Biological Assays

In Vitro Palmitoylation

[0645] Recombinant GST-TEAD2 or His.sub.6TEAD2 (500 ng) protein was pre-incubated with the compounds at indicated concentrations for 15 min. and then incubated with 1 μM of alkyne palmitoyl-5 CoA (Cayman Chemical) for 30 min or 50 mM MES, pH 6.4, followed by Click reaction with biotin-azide as previously described (Zheng, B. et al., J. Am. Chem. Soc., 2013, 135, 7082-7085). Click reaction was performed with 100 μM biotin-azide, 1 mM tris(2-carboxyethyl) phosphine hydrochloride (TCEP), 100 μM tris[(1-benzyl-1H-1,2,3-triazol-4-yl) methyl] amine (TBTA) and 1 mM CuSO.sub.4 for 1 h at RT.

[0646] The reactions were terminated by the addition of 12 μL of 6×SDS-sample loading buffer (50 mM Tris-HCl, pH 6.8, 6% SDS, 48% Glycerol, 0.03% Bromophenol Blue, 30 mM EDTA, 9% MeSH). Samples were analysed by SDS-PAGE and Western blot was performed by probing with streptavidin HRP and histidine HRP antibodies independently. Bands intensity obtained from streptavidin blot were quantified using BIORAD, Gel doc system and the percentage of inhibition of Tead2 auto palmitoylation is determined by comparing to the DMSO control treated samples.

[0647] These compounds were tested for activity in inhibiting TEAD2 palmitoylation in the assay described above. The data for the compounds is provided in below table as a percentage of inhibition of TEAD2 palmitoylation by the compound at a concentration of 10 PM.

Cell Proliferation

[0648] HuH7 cells (or other cells) are cultured in DMEM supplemented with 10% FBS. The cells are seeded in 96-wells with 5000 cells/well density. After cell attached to the wells, compounds in DMSO solution were added (1% DMSO concentration) to the cells with serial dilutions for the indicated final concentration. The cells were further incubated for 3 days. The cell viability is then determined using CellTiter Glo, MTT or crystal violet staining. The inhibition curve is plotted by using GraphPad.

qRT-PCR

[0649] YAP target gene expression was analyzed with a LightCycler 480 (Roche). Total RNA was isolated from cells using TRIzol (Life Technologies) and then used to produce cDNA with the Transcriptor First Strand cDNA Synthesis Kit (Roche). The resulting cDNA was then used in reactions with the LightCycler 480 SYBR Green I Master mix (Roche) with probes detecting CTGF or CYR61, and GAPDH.

CMP Assay

[0650] 7-Diethylamino-3-(4′-Maleimidylphenyl)-4-Methylcoumarin (CPM), which reacts with thiol of CoA liberated in the enzymatic reaction, and gives fluorescent signal (excitation ˜350-380, emission-460-480). The assay detects the product (free CoA) which is produced from palmitoyl-CoA as a method to detect the enzymatic activity. Test compounds that inhibit TEAD activity are therefore able to block the CMP fluorescent signal.

[0651] TEAD2/4 protein (10 μL of a 50 ng/μL solution) and a solution the test compound (0.5 μL, variable concentration) were pre-incubated for 30 min at r.t. A mixture prepared from MES pH 6.4 buffer (6.5 μL of a 50 mM solution), EDTA (1 μL of a 20 mM solution), palmitoyl-CoA (1 μL of a 20 μM solution), and 7-diethylamino-3-(4′-maleimidylphenyl)-4-methylcoumarin (1 μL of a 10 μM solution) was added and the resulting mixture was mixed well using a pipette. The solution was then incubated at r.t. for 30-120 min. in the dark, and fluorescence was detected at 350 nm every 30 min. until the fluorescence signal is saturated. An IC.sub.50 for the ability of the compound to inhibit fluorescence is calculated from the results.

[0652] Results of the biological assays are shown in FIGS. 3-12 and Table 1 and Table 2.

Compounds Active as TEAD Palmitoylation Inhibitors

[0653] The Example compounds were tested for activity in inhibiting TEAD2 palmitoylation in the assay and CMP assay described above. The data for the compounds provided in Table 1 as a percentage of inhibition of TEAD2 palmitoylation by the compound at a concentration of 10 μM or the IC50 in the CMP assay.

TABLE-US-00036 TABLE 1 Activity of Compounds as TEAD Palmitoylation Inhibitors % of inhibition of TEAD2 Compound structure palmitoylation at 10 μM CMP IC.sub.50 (μM) [01334]  50 [01335] 1025 [01336]  70 5.09 [01337]   5 [01338]   5 [01339]  80 [01340]  20 [01341]  20 [01342]  20 [01343]   8 [01344]  80 [01345]  100 [01346]  100

TABLE-US-00037 TABLE 2 Activity of Compounds as TEAD2 Palmitoylation Inhibitors % of inhibition of Cmpd. TEAD2 palmitoylation CP No Structure at 10 μM or IC.sub.50 μM  51  1 [01347]  10  54  2 [01348]  0  57  3 [01349]  0  68  4 [01350]  0  70  5 [01351]  0  79  6 [01352]  0  85  7 [01353]  30 104  8 [01354] NA 201  9 [01355]  76 225  10 [01356]  0 264  11 [01357]  0 238  12 [01358]  85 347  13 [01359]  26 352  14 [01360]  0 375  15 [01361]  12 354  16 [01362]  0 381  17 [01363]  7 351  18 [01364]  35 406  19 [01365]  35  86  20 [01366] NA  87  21 [01367] NA 231  22 [01368]  74  82  23 [01369] NA  55  24 [01370]  56  52  25 [01371]  90  58  26 [01372]  90  59  27 [01373]  90  60  28 [01374]  10  61  29 [01375]  90  62  30 [01376]  91  64  31 [01377] 99, 84, 82, 0.377 μM  65  32 [01378]  60  66  33 [01379]  50  67  34 [01380]  14  69  35 [01381] 63, 86  71  36 [01382] 100  80  37 [01383]  30  83  38 [01384]  7  88  39 [01385]  59  89  40 [01386]  43  93  41 [01387]  52  98  42 [01388] NA  99  43 [01389] NA 100  44 [01390] NA 101  45 [01391] NA 102  46 [01392]  76 103  47 [01393]  83 106  48 [01394]  87 107  49 [01395] NA 108  50 [01396]  0 113  51 [01397]  79 114  52 [01398]  79 115  53 [01399]  5 116  54 [01400] NA 117  55 [01401] NA 118  56 [01402]  0 121  57 [01403] NA 122  58 [01404]  60 124  59 [01405]  99 125  60 [01406] 100 126  61 [01407]  70 127  62 [01408]  65 128  63 [01409] NA 129  64 [01410]  0 130  65 [01411]  74 131  66 [01412]  25 134  67 [01413] NO 135  68 [01414] YES 136  69 [01415] NO 138  70 [01416] NO 139  71 [01417] YES 140  72 [01418] NO 141  73 [01419] NO 142  74 [01420]  31 143  75 [01421]  63 144  76 [01422]  34 145  77 [01423]  52 146  78 [01424] NO 148  79 [01425]  45 149  80 [01426]  40 151  81 [01427]  78 156  82 [01428]  67 157  83 [01429]  65 158  84 [01430]  98 159  85 [01431]  20 160  86 [01432]  54 161  87 [01433]  4 162  88 [01434]  12 163  89 [01435]  90 168  90 [01436] 98, 0.446 μM 169  91 [01437]  97 170  92 [01438]  90 172  93 [01439]  72 173  94 [01440]  91 174  95 [01441]  97 177  96 [01442]  96 178  97 [01443]  60 182 294  98 [01444]  89 183  99 [01445]  85 184 100 [01446] 100, 0.207 μM 185 101 [01447]  62 186 102 [01448]  77 187 103 [01449]  53 191 104 [01450]  80 192 105 [01451]  96 194 106 [01452]  0 195 107 [01453]  14 197 108 [01454]  86 198 109 [01455] 100, 0.346 μM 199 110 [01456]  85 200 111 [01457]  80 202 112 [01458] 100, 0.268 μM 203 113 [01459] 100 204 114 [01460]  98 205 115 [01461]  67 206 116 [01462]  91 207 117 [01463]  9 210 118 [01464]  78 211 119 [01465] 100, 0.106 μM 212 120 [01466]  79 213 121 [01467]  80 214 122 [01468]  95 215 123 [01469]  88 217 124 [01470]  86 218 125 [01471] 96, 0.771 μM 219 126 [01472]  86 220 127 [01473]  27 221 128 [01474]  92 226 129 [01475]  41 227 130 [01476] 100 228 131 [01477]  37 233 132 [01478] 100 236 133 [01479]  93 240 134 [01480]  0 241 135 [01481] 100 243 136 [01482]  99 244 137 [01483]  99 245 138 [01484]  24 246 139 [01485] 95, 0.312 μM 247 140 [01486]  99 248 141 [01487]  95 249 142 [01488]  65 250 143 [01489]  22 252 144 [01490] 100 254 145 [01491] 61, 84 255 146 [01492]  64 258 147 [01493]  70 259 148 [01494] 56, 69 260 149 [01495]  40 261 150 [01496] 100 263 151 [01497] 101 266 152 [01498] 102 267 153 [01499] 100 268 154 [01500] 58, 43 270 155 [01501]  99 271 156 [01502]  92 272 157 [01503]  80 273 158 [01504] 100 274 159 [01505]  41 275 160 [01506]  84 276 161 [01507] 17, 43 277 162 [01508] 25, 88 278 163 [01509]  85 279 164 [01510]  20 282 165 [01511]  85 284 166 [01512]  98 285 167 [01513]  43 286 168 [01514] 97, 0.173 μM 287 169 [01515]  42 288 170 [01516]  62 289 171 [01517]  75 290 172 [01518] 100 291 173 [01519]  51 292 174 [01520]  85 293 175 [01521]  70 294 176 [01522]  89 295 177 [01523]  56 296 178 [01524] 100, 0.227 μM 297 179 [01525] 92, 35 298 180 [01526]  81 299 181 [01527] 49, 41 300 182 [01528]  54 301 183 [01529] 100, 96 302 184 [01530]  71 303 185 [01531] 66, 91 304 186 [01532]  76 305 187 [01533]  57 306 188 [01534] 101 307 189 [01535]  34 308 190 [01536]  85 309 191 [01537]  85 310 192 [01538]  99 311 193 [01539]  86 312 194 [01540]  20 313 195 [01541]  0 314 196 [01542] 100 315 197 [01543] 100 316 198 [01544]  99 317 199 [01545]  6 318 200 [01546]  32 319 201 [01547]  43 320 202 [01548]  49 321 203 [01549]  95 322 204 [01550]  99 323 205 [01551]  74 324 206 [01552]  52 325 207 [01553]  99 326 208 [01554] 100 327 209 [01555]  54 328 210 [01556] 100 329 211 [01557]  67 330 212 [01558]  77 331 213 [01559]  90 333 214 [01560] 88, 73 334 215 [01561]  87 335 216 [01562]  89 336 217 [01563]  55 337 218 [01564]  0 338 219 [01565]  0 339 220 [01566]  10 340 221 [01567]  61 341 222 [01568]  45 342 223 [01569] 100 343 224 [01570]  81 344 225 [01571]  84 345 226 [01572]  17 346 227 [01573]  58 349 228 [01574]  89 350 229 [01575]  91 353 230 [01576]  0 355 231 [01577]  0 356 232 [01578]  33 357 233 [01579]  9 358 234 [01580]  64 359 235 [01581]  84 360 236 [01582]  62 361 237 [01583]  93 362 238 [01584] 100 363 239 [01585] 98, 100 364 240 [01586]  62 366 241 [01587] 100 367 242 [01588] 35, 58 369 243 [01589]  67 370 244 [01590]  8 371 245 [01591]  87 372 246 [01592]  99 373 247 [01593]  95 376 248 [01594]  32 377 249 [01595]  1 379 250 [01596] 89, 0.274 μM 380 251 [01597]  27 382 252 [01598] 100, 0.053 μM 383 253 [01599] 100, 0.099 μM 384 254 [01600] 100, 0.297 μM 385 255 [01601]  50 386 256 [01602]  46 387 257 [01603]  55 388 258 [01604]  0 389 259 [01605]  83 392 260 [01606]  71 393 261 [01607]  98 394 262 [01608]  85 395 263 [01609]  59 396 264 [01610]  0 397 265 [01611]  78 398 266 [01612]  81 407 267 [01613]  36 408 268 [01614]  10 420 269 [01615] 100  72 270 [01616]  23  94 271 [01617] NA 111 272 [01618]  77 112 273 [01619]  50 120 274 [01620]  50 123 275 [01621]  76 164 276 [01622]  52 208 277 [01623]  0 209 278 [01624]  28 605 429 [01625]  47 606 430 [01626]  63 607 431 [01627]  37 653 432 [01628]  24 109 279 [01629] NA 230 280 [01630]  0 152 281 [01631]  98 155 282 [01632]  14 153 283 [01633] 89, 0.064 μM 154 284 [01634]  97 175 285 [01635]  9 540 440 [01636]  75 559 441 [01637]  79 119 286 [01638]  98  90 287 [01639]  17  96 288 [01640] NA 105 289 [01641] NA 110 290 [01642]  99 132 291 [01643]  14 133 292 [01644]  67 176 293 [01645]  86 216 294 [01646]  96 229 295 [01647]  53 237 296 [01648]  88 239 297 [01649]  69 348 298 [01650] 100 378 299 [01651]  97 453 [01652]  0

TABLE-US-00038 TABLE 3 Activity of Compounds as TEAD2 Palmitoylation Inhibitors % of inhibition of TEAD2 TEAD2 palmitoylation palmitoylation CP Structure at 10 μM IC50 CP- 472 [01653] 1 CP- 473 [01654] 50 CP- 516 [01655] 20 CP- 521 [01656] 93 1.45 CP- 522 [01657] 96 1.53 CP- 525 [01658] PPT CP- 526 [01659] 23 CP- 528 [01660] 76 0.38 CP- 529 [01661] 29 CP- 531 [01662] 20 CP- 534 [01663] 31 CP- 535 [01664] 54 CP- 536 [01665] 84 CP- 537 [01666] 73 CP- 538 [01667] 85 0.68 CP- 540 [01668] 75 CP- 541 [01669] 80 CP- 542 [01670] 49 CP- 543 [01671] 98 CP- 544 [01672] 98 CP- 545 [01673] 6 CP- 546 [01674] 97 CP- 547 [01675] 18 CP- 548 [01676] 86 0.45 CP- 549 [01677] 85 2.4 CP- 550 [01678] 96 0.79 CP- 551 [01679] 91 0.002 CP- 552 [01680] 74 CP- 553 [01681] 100 0.59 CP- 554 [01682] 96 0.01 CP- 555 [01683] 100 0.01 CP- 556 [01684] 61 CP- 557 [01685] 34 CP- 558 [01686] 66 CP- 559 [01687] 79 CP- 560 [01688] 90 0.011 CP- 561 [01689] 90 CP- 563 [01690] 80 CP- 564 [01691] 89 CP- 565 [01692] 100 0.51 CP- 566 [01693] 99 0.38 CP- 567 [01694] 6 CP- 568 [01695] 46 CP- 569 [01696] 59 CP- 570 [01697] 73 0.65 CP- 571 [01698] 94 0.36 CP- 572 [01699] 72 CP- 573 [01700] 74 CP- 574 [01701] 91 CP- 575 [01702] 47 CP- 576 [01703] 42 CP- 577 [01704] 79 CP- 578 [01705] 31 CP- 579 [01706] 61 CP- 580 [01707] 58 CP- 581 [01708] 40 CP- 582 [01709] 0 CP- 583 [01710] 96 0.23 CP- 584 [01711] 85 0.21 CP- 585 [01712] 86 0.32 CP- 586 [01713] 40 CP- 587 [01714] 36 CP- 588 [01715] 36 CP- 589 [01716] 97 1.57 CP- 590 [01717] 96 0.22 CP- 591 [01718] 88 CP- 592 [01719] 40 CP- 593 [01720] 78 0.03 CP- 594 [01721] 46 CP- 595 [01722] 51 CP- 596 [01723] 48 CP- 597 [01724] 63 CP- 598 [01725] 74 0.05 CP- 599 [01726] 57 CP- 600 [01727] 37 CP- 601 [01728] 46 CP- 602 [01729] 5 CP- 603 [01730] 83 CP- 605 [01731] 47 CP- 606 [01732] 63 CP- 607 [01733] 37 CP- 608 [01734] 43 CP- 609 [01735] 54 CP- 612 [01736] 86 CP- 613 [01737] 83 CP- 614 [01738] 83 CP- 615 [01739] 82 CP- 616 [01740] 73 CP- 617 [01741] 76 CP- 618 [01742] 31 CP- 619 [01743] 96 0.75 CP- 620 [01744] 0 CP- 621 [01745] 47 CP- 622 [01746] 94 CP- 623 [01747] 73 CP- 624 [01748] 15 CP- 625 [01749] 87 CP- 626 [01750] 87 0.382 CP- 627 [01751] 51 CP- 628 [01752] 40 CP- 629 [01753] 24 CP- 630 [01754] 39 CP- 631 [01755] 81 CP- 632 [01756] 73 CP- 633 [01757] 25 CP- 634 [01758] 32 CP- 635 [01759] 27 CP- 636 [01760] 68 CP- 637 [01761] 5 CP- 638 [01762] 67 CP- 640 [01763] 20 CP- 641 [01764] 69 CP- 642 [01765] 55 CP- 643 [01766] 89 CP- 646 [01767] 39 CP- 647 [01768] 87 CP- 648 [01769] 89 CP- 649 [01770] 99 CP- 650 [01771] 93 CP- 651 [01772] 85 CP- 652 [01773] 37 CP- 653 [01774] 24 CP- 654 [01775] 36 CP- 655 [01776] 97 CP- 656 [01777] 90 CP- 657 [01778] 18 CP- 659 [01779] 46 CP- 660 [01780] 66 CP- 661 [01781] 77 CP- 662 [01782] 88 CP- 663 [01783] 45 CP- 664 [01784] 50 CP- 665 [01785] 96 CP- 666 [01786] 79 CP- 669 [01787] 75 CP- 671 [01788] 97 CP- 672 [01789] 55 CP- 673 [01790] 15 CP- 675 [01791] 83 CP- 676 [01792] 97 CP- 677 [01793] 96 CP- 678 [01794] 59 CP- 679 [01795] 81 CP- 680 [01796] 52 CP- 681 [01797] 8 CP- 682 [01798] 51 CP- 688 [01799] 17 CP- 694 [01800] 79 CP- 644 [01801]

[0654] Various modifications of the invention, in addition to those described herein, will be apparent to those skilled in the art from the foregoing description. Such modifications are also intended to fall within the scope of the appended claims. Each reference, including without limitation all patent, patent applications, and publications, cited in the present application is incorporated herein by reference in its entirety.