6-membered heterocyclic derivatives and pharmaceutical composition comprising the same

Abstract

A compound represented by Formula (I): ##STR00001##
wherein ##STR00002##
or the like,
Y.sup.1 is O or the like; Z.sup.1 is C(R.sup.4) or N; Z.sup.2a is C(R.sup.5a) or the like; Z.sup.3a is C(R.sup.6) or the like; R.sup.4, R.sup.5a and R.sup.6 are each independently a hydrogen atom or the like; R.sup.1 is substituted or unsubstituted aromatic carbocyclyl or the like; R.sup.2a, R.sup.2b, R.sup.2c and R.sup.2d are each independently a hydrogen atom or the like; X is N(R.sup.7a) or the like; R.sup.7a is a hydrogen atom or the like; R.sup.3 is ##STR00003##
or the like,
Ring B is a 6-membered aromatic carbocycle or the like; R.sup.9a and R.sup.10a are each independently halogen or the like; n is an integer from 1 to 5; m is an integer from 0 to 4; and p1 is an integer from 0 to 3,
or a pharmaceutically acceptable salt thereof.

Claims

1. A method for treating a disease associated with the P2X7 receptor, comprising administering an effective amount of a compound selected from the group consisting of: ##STR01437## ##STR01438## ##STR01439## ##STR01440## or a pharmaceutically acceptable salt thereof, to a patient in need thereof.

2. The method according to claim 1, wherein the compound is ##STR01441## or a pharmaceutically acceptable salt thereof.

3. The method according to claim 1, wherein the compound is ##STR01442## or a pharmaceutically acceptable salt thereof.

4. The method according to claim 1, wherein the compound is ##STR01443## or a pharmaceutically acceptable salt thereof.

5. The method according to claim 1, wherein the compound is ##STR01444## or a pharmaceutically acceptable salt thereof.

6. The method according to claim 1, wherein the compound is ##STR01445## or a pharmaceutically acceptable salt thereof.

Description

MODE FOR CARRYING OUT THE INVENTION

(1) Terms used in this description are explained below. Each term, unless otherwise indicated, has the same meaning when it is used alone or together with other terms.

(2) The term “consist of” means having only a component.

(3) The term “comprise” means that an element that is not described is not excluded without limitations to a component.

(4) “Halogen” includes a fluorine atom, a chlorine atom, a bromine atom and an iodine atom. A fluorine atom and a chlorine atom are preferable.

(5) “Alkyl” includes a C1 to C15, preferably C1 to C10, more preferably C1 to C6 and further preferably C1 to C4 linear or branched hydrocarbon group. For example, it includes methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, neopentyl, n-hexyl, isohexyl, n-heptyl, isoheptyl, n-octyl, isooctyl, n-nonyl, n-decyl and the like.

(6) A preferred embodiment of “alkyl” is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl or n-pentyl. A more preferred embodiment is methyl, ethyl, n-propyl, isopropyl or tert-butyl.

(7) “Alkenyl” includes a C2 to C15, preferably C2 to C10, more preferably C2 to C6 and further preferably C2 to C4 linear or branched hydrocarbon group having one or more double bond(s) at any position(s). For example, it includes vinyl, allyl, propenyl, isopropenyl, butenyl, isobutenyl, prenyl, butadienyl, pentenyl, isopentenyl, pentadienyl, hexenyl, isohexenyl, hexadienyl, heptenyl, octenyl, nonenyl, decenyl, undecenyl, dodecenyl, tridecenyl, tetradecenyl, pentadecenyl and the like.

(8) A preferred embodiment of “alkenyl” is vinyl, allyl, propenyl, isopropenyl or butenyl.

(9) “Alkynyl” includes a C2 to C10, preferably C2 to C8, more preferably C2 to <16 and further preferably C2 to C4 linear or branched hydrocarbon group having one or more triple bond(s) at any position(s). For example, it includes ethynyl, propynyl, butynyl, pentynyl, hexynyl, heptynyl, octynyl, nonynyl, decynyl and the like. Furthermore, it may have double bond(s) at any position(s).

(10) A preferred embodiment of “alkynyl” is ethynyl, propynyl, butynyl or pentynyl.

(11) “Aromatic carbocycle” means a cyclic aromatic hydrocarbon ring which is monocyclic or polycyclic having two or more rings. For example, it includes benzene, naphthalene, anthracene, phenanthrene and the like.

(12) A preferred embodiment, of “aromatic carbocycle” is benzene.

(13) “Aromatic carbocyclyl” means a cyclic aromatic hydrocarbon group which is monocyclic or polycyclic having two or more rings. For example, it includes phenyl, naphthyl, anthryl, phenanthryl and the like.

(14) A preferred embodiment of “aromatic carbocyclyl” is phenyl.

(15) “Non-aromatic carbocycle” means a cyclic saturated hydrocarbon ring or a cyclic unsaturated non-aromatic hydrocarbon ring, which is monocyclic or polycyclic having two or more rings. “Non-aromatic carbocycle”, which is polycyclic having two or more rings, includes a fused ring wherein a non-aromatic carbocycle, which is monocyclic or polycyclic having two or more rings, is fused with a ring of the above “aromatic carbocycle”.

(16) In addition, the “non-aromatic carbocycle” also includes a ring having a bridge or a ring to form a spiro ring as follows.

(17) ##STR00035##

(18) A non-aromatic carbocycle which is monocyclic is preferably C3 to C16, more preferably C3 to C12 and further preferably C4 to C8 carbocycle. For example, it includes cyclopropane, cyclobutane, cyclopentane, cyclohexane, cycloheptane, cyclooctane, cyclononane, cyclodecane, cyclopropane, cyclobutene, cyclopentene, cyclohexene, cycloheptene, cyclohexadiene and the like.

(19) A non-aromatic carbocycle which is polycyclic having two or more rings includes, for example, indane, indene, acenaphthalene, tetrahydronaphthalene, fluorene and the like.

(20) “Non-aromatic carbocyclyl” means a cyclic saturated hydrocarbon group or a cyclic unsaturated non-aromatic hydrocarbon group, which is monocyclic or polycyclic having two or more rings. “Non-aromatic carbocyclyl”, which is polycyclic having two or more rings, includes a fused ring group wherein a non-aromatic carbocyclyl, which is monocyclic or polycyclic having two or more rings, is fused with a ring of the above “aromatic carbocyclyl”.

(21) In addition, the “non-aromatic carbocyclyl” also includes a group having a bridge or a group to form a spiro ring as follows:

(22) ##STR00036##

(23) A non-aromatic carbocyclyl which is monocyclic is preferably C3 to C10, more preferably C3 to C12 and further preferably C4 to C8 carbocyclyl. For example, it includes cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, eyclononyl, cyclodecyl, cyclopropenyl, cyclobutenyl, cyclopentenyl, cyclohexenyl, cycloheptenyl, cyclohexadienyl and the like.

(24) A non-aromatic carbocyclyl which is polycyclic having two or more rings includes, for example, indanyl, indenyl, acenaphthyl, tetrahydronaphthyl, fluorenyl and the like.

(25) “Aromatic heterocyclo” means an aromatic ring, which is monocyclic or polycyclic having two or more rings, containing one or more and same or different of heteroatom(s) selected independently from O, S and N.

(26) “Aromatic heterocyclo”, which is polycyclic having two or more rings, includes a fused ring wherein an aromatic heterocycle, which is monocyclic or polycyclic having two or more rings, is fused with a ring of the above “aromatic carbocycle”.

(27) An aromatic heterocycle which is monocyclic is preferably a 5- to 8-membered and more preferably 5- to 6-membered ring. For example, it includes pyrrole, imidazole, pyrazole, pyridine, pyridazine, pyrimidine, pyrazine, triazole, triazine, tetrazole, furan, thiophene, isoxazole, oxazole, oxadiazole, isothiazole, thiazole, thiadiazole and the like.

(28) An aromatic heterocycle which is bicyclic includes, for example, indole, isoindole, indazole, indolizine, quinoline, isoquinoline, cinnoline, phthalazine, quinazoline, naphthyridine, quinoxaline, purine, pteridine, benzimidazole, benzisoxazole, benzoxazole, benzoxadiazole, benzisothiazole, benzothiazole, benzothiadiazole, benzofuran, isobenzofuran, benzothiophene, benzotriazole, imidazopyridine, triazolopyridine, imidazothiazole, pyrazinopyridazine, oxazolopyridine, thiazolopyridine and the like.

(29) An aromatic heterocycle which is polycyclic having three or more rings includes, for example, carbazole, acridine, xanthene, phenothiazine, phenoxathiine, phenoxazine, dibenzofuran and the like.

(30) “Aromatic heterocyclyl” means an aromatic cyclyl, which is monocyclic or polycyclic having two or more rings, containing one or more and same or different of heteroatom(s) selected independently from O, S and N.

(31) “Aromatic heterocyclyl”, which is polycyclic having two or more rings, includes a fused ring group wherein an aromatic heterocyclyl, which is monocyclic or polycyclic having two or more rings, is fused with a ring of the above “aromatic carbocyclyl”.

(32) An aromatic heterocyclyl which is monocyclic is preferably a 5- to 8-membered and more preferably 5- to 6-membered ring. For example, it includes pyrrolyl, imidazolyl, pyrazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazolyl, triazinyl, tetrazolyl, furyl, thienyl, isoxazolyl, oxazolyl, oxadiazolyl, isothiazolyl, thiazolyl, thiadiazolyl and the like.

(33) An aromatic heterocyclyl which is bicyclic includes, for example, indolyl, isoindolyl, indazolyl, indolizinyl, quinolinyl, isoquinolinyl, cinnolinyl, phthalazinyl, quinazolinyl, naphthyridinyl, quinoxalinyl, purinyl, pteridinyl, benzimidazolyl, benzisoxazolyl, benzoxazolyl, benzoxadiazolyl, benzisothiazolyl, benzothiazolyl, benzothiadiazolyl, benzofuryl, isobenzofuryl, benzothienyl, benzotriazolyl, imidazopyridyl, triazolopyridyl, imidazothiazolyl, pyrazinopyridazinyl, oxazolopyridyl, thiazolopyridyl and the like.

(34) An aromatic heterocyclyl which is polycyclic having three or more rings includes, for example, carbazolyl, acridinyl, xanthenyl, phenothiazinyl, phenoxathiinyl, phenoxazinyl, dibenzofuryl and the like.

(35) “Non-aromatic heterocycle” means a non-aromatic ring, which is monocyclic or polycyclic having two or more rings, containing one or more and same or different of heteroatom(s) selected independently from O, S and N.

(36) “Non-aromatic heterocycle”, which is polycyclic having two or more rings, includes a fused ring wherein a non-aromatic heterocycle, which is monocyclic or polycyclic having two or more ring(s), is fused with a ring of the above “aromatic carbocycle”, “non-aromatic carbocycle” and/or “aromatic heterocycle”. The non-aromatic heterocycle, which is polycyclic having two or more rings, further includes a fused ring wherein an aromatic heterocycle, which is monocyclic or polycyclic having two or more rings, is fused with a ring of the above “non-aromatic carbocycle”.

(37) In addition, the “non-aromatic heterocycle” also includes a ring having a bridge or a ring to form a spiro ring as follows.

(38) ##STR00037##

(39) A non-aromatic heterocycle which is monocyclic is preferably a 3- to 8-membered and more preferably 5- to 6-membered ring. For example, it includes dioxane, thiirane, oxirane, oxetane, oxathiolane, azetidine, thiane, thiazolidine, pyrrolidine, pyrroline, imidazolidine, imidazoline, pyrazolidine, pyrazoline, piperidine, piperazine, morpholine, thiomorpholine, dihydropyridine, tetrahydropyridino, tetrahydrofuran, tetrahydropyrane, dihydrothiazole, tetrahydrothiazole, tetrahydroisothiazole, dihydrooxazine, hexahydroazepine, tetrahydrodiazepine, tetrahydropyridazine, hexahydropyrimidine, dioxolane, dioxazine, aziridine, dioxoline, oxepane, thiolane, thiine, thiazine and the like.

(40) A non-aromatic heterocycle which is polycyclic having two or more rings includes, for example, indoline, isoindolinel, chromane, isochromane and the like.

(41) “Non-aromatic heterocyclyl” means a non-aromatic cyclyl, which is monocyclic or polycyclic having two or more rings, containing one or more and same or different of heteroatom(s) selected independently from O, S and N.

(42) “Non-aromatic heterocyclyl”, which is polycyclic having two or more rings, includes a fused ring group wherein a non-aromatic heterocycle, which is monocyclic or polycyclic having two or more ring(s), is fused with a ring of the above “aromatic carbocyclyl”, “non-aromatic carbocyclyl” and/or “aromatic heterocyclyl”. The non-aromatic heterocyclyl, which is polycyclic having two or more rings, further includes a fused ring wherein an aromatic heterocyclyl, which is monocyclic or polycyclic having two or more rings, is fused with a ring of the above “non-aromatic carbocyclyl”.

(43) In addition, the “non-aromatic heterocyclyl” also includes a group having a bridge or a group to form a spiro ring as follows:

(44) ##STR00038##

(45) A non-aromatic heterocyclyl which is monocyclic is preferably a 3- to 8-membered and more preferably 5- to 6-membered ring. For example, it includes dioxanyl, thiiranyl, oxiranyl, oxetanyl, oxathiolanyl, azetidinyl, thienyl, thiazolidinyl, pyrrolidinyl, pyrrolinyl, imidazolidinyl, imidazolinyl, pyrazolidinyl, pyrazolinyl, piperidinyl, piperazinyl, morpholinyl, morpholino, thiomorpholinyl, thiomorpholino, dihydropyridinyl, tetrahydropyridinyl, tetrahydrofuryl, tetrahydropyranyl, dihydrothiazolinyl, totrahydrothiazolinyl, tetrahydroisothiazolinyl, dihydrooxazinyl, hexahydroazepinyl, tetrahydrodiazepinyl, tetrahydropyridazinyl, hexahydropyrimidinyl, dioxolanyl, dioxazinyl, aziridinyl, dioxolinyl, oxepanyl, thiolanyl, thiinyl, thiazinyl and the like.

(46) A non-aromatic heterocyclyl which is polycyclic having two or more rings includes, for example, indolinyl, isoindolinyl, chromanyl, isochromanyl and the like.

(47) “Alkyloxy” means a group wherein the above “alkyl” is bonded to an oxygen atom. For example, it includes methyloxy, ethyloxy, n-propyloxy, isopropyloxy, n-butyloxy, tert-butyloxy, isobutyloxy, sec-butyloxy, pentyloxy, isopentyloxy, hexyloxy and the like.

(48) A preferred embodiment of “alkyloxy” is methyloxy, ethyloxy, n-propyloxy, isopropyloxy or tert-butyloxy.

(49) “Alkenyloxy” means a group wherein the above “alkenyl” is bonded to an oxygen atom. For example, it includes vinyloxy, allyloxy, 1-propenyloxy, 2-butenyloxy, 2-pentenyloxy, 2-hexenyloxy, 2-heptenyloxy, 2-octenyloxy and the like.

(50) “Alkynyloxy” means a group wherein the above “alkynyl” is bonded to an oxygen atom. For example, it includes ethynyloxy, 1-propynyloxy, 2-propynyloxy, 2-butynyloxy, 2-pentynyloxy. 2-hexynyloxy, 2-heptynyloxy, 2-octynyloxy and the like.

(51) “Alkylsulfanyl” means a group wherein a hydrogen atom bonded to a sulfur atom of a sulfanyl group is replaced with the above “alkyl”. For example, it includes methylsulfanyl, ethylsulfanyl, n-propylsulfanyl, isopropylsulfanyl and the like.

(52) “Alkenylsulfonyl” means a group wherein a hydrogen atom bonded to a sulfur atom of a sulfanyl group is replaced with the above “alkenyl”. For example, it includes ethylenylsulfanyl, propenylsulfanyl and the like.

(53) “Alkynylsulfanyl” means a group wherein a hydrogen atom bonded to a sulfur atom of a sulfanyl group is replaced with the above “alkynyl”. For example, it includes ethynylsulfanyl, propynylsulfanyl and the like.

(54) “Alkylamino” means a group wherein a hydrogen atom attached to a nitrogen atom of an amino group is replaced with the above “alkyl”. For example, it includes methylamino, ethylamino, isopropylamino and the like. Another hydrogen atom attached to the nitrogen atom of the amino group may be replaced with the above “alkyl”.

(55) A preferred embodiment of “alkylamino” is methylamino or ethylamino.

(56) “Alkenylamino” means a group wherein a hydrogen atom attached to a nitrogen atom of an amino group is replaced with the above “alkenyl”. For example, it includes ethylenylamino, propenylamino and the like. Another hydrogen atom attached to the nitrogen atom of the amino group may be replaced with the above “alkyl”.

(57) “Alkynylamino” means a group wherein a hydrogen atom attached to a nitrogen atom of an amino group is replaced with the above “alkynyl”. For example, it includes ethynylamino, propynylamino and the like. Another hydrogen atom attached to the nitrogen atom of the amino group may be replaced with the above “alkyl”.

(58) “Alkylcarbonyl” means a group wherein the above “alkyl” is bonded to a carbonyl group. For example, it includes methylcarbonyl, ethylcarbonyl, propylcarbonyl, isopropylcarbonyl, tert-butylcarbonyl, isobutylcarbonyl, sec-butylcarbonyl, pentylcarbonyl, isopenthylcarbonyl, hexylcarbonyl and the like.

(59) A preferred embodiment of “alkylcarbonyl” is methylcarbonyl, ethylcarbonyl or n-propylcarbonyl.

(60) “Alkenylcarbonyl” means a group wherein the above “alkenyl” is bonded to a carbonyl group. For example, it includes ethylenylcarbonyl, propenylcarbonyl and the like.

(61) “Alkynylcarbonyl” means a group wherein the above “alkynyl” is bonded to a carbonyl group. For example, it includes ethynylcarbonyl, propynylcarbonyl and the like.

(62) “Alkylsulfonyl” means a group wherein the above “alkyl” is bonded to a sulfonyl group. For example, it includes methylsulfonyl, ethylsulfonyl, propylsulfonyl, isopropylsulfonyl, tert-butylsulfonyl, isobutylsulfonyl, see-butylsulfonyl and the like.

(63) A preferred embodiment, of “alkylsulfonyl” is methylsulfonyl or ethylsulfonyl.

(64) “Alkenylsulfonyl” means a group wherein the above “alkenyl” is bonded to a sulfonyl group. For example, it includes ethylenylsulfonyl, propenylsulfonyl and the like.

(65) “Alkynylsulfinyl” means a group wherein the above “alkynyl” is bonded to a sulfonyl group. For example, it includes ethynyl sulfonyl, propynylsulfonyl and the like.

(66) “Alkylcarbonyloxy” means a group wherein the above “alkylcarbonyl” is bonded to an oxygen atom. For example, it includes methylcarbonyloxy, ethylcarbonyloxy, propylcarbonyloxy, isopropylcarbonyloxy, tert-butylcarbonyloxy, isobutylcarbonyloxy, sec-butylcarbonyloxy and the like.

(67) A preferred embodiment of “alkylcarbonyloxy” is methylcarbonyloxy or ethylcarbonyloxy.

(68) “Alkenylcarbonyloxy” means a group wherein the above “alkenylcarbonyl” is bonded to an oxygen atom. For example, it includes ethylenylcarbonyloxy, propenylcarbonyloxy and the like.

(69) “Alkynylcarbonyloxy” means a group wherein the above “alkynylcarbonyl” is bonded to an oxygen atom. For example, it includes ethynylcarbonyloxy, propenylcarbonyloxy and the like.

(70) “Alkyloxycarbonyl” means a group wherein the above “alkyloxy” is bonded to a carbonyl group. For example, it includes methyloxycarbonyl, ethyloxycarbonyl, propyloxycarbonyl, isopropyloxycarbonyl, tert-butyloxycarbonyl, isobutyloxycarbonyl, sec-butyloxycarbonyl, penthyloxycarbonyl, isopenthyloxycarbonyl, hexyloxycarbonyl and the like.

(71) A preferred embodiment of “alkyloxycarbonyl” is methyloxycarbonyl, ethyloxycarbonyl or propyloxycarbonyl.

(72) “Alkenyloxycarbonyl” means a group wherein the above “alkenyloxy” is bonded to a carbonyl group. For example, it includes ethylenyloxycarbonyl, propenyloxycarbonyl and the like.

(73) “Alkynyloxycarbonyl” means a group wherein the above “alkynyloxy” is bonded to a carbonyl group. For example, it includes ethynyloxycarbonyl, propynyloxycarbonyl and the like.

(74) “Alkylsulfonyloxy” means a group wherein the above “alkylsulfonyl” is bonded to an oxygen atom. For example, it includes methylsulfonyloxy, arylsulfonyloxy, propylsulfonyloxy, isopropylsulfonyloxy, tert-butylsulfonyloxy, isobutyl sulfonyloxy, sec-butylsulfonyloxy and the like.

(75) A preferred embodiment of “alkylsulfonyloxy” is methylsulfonyloxy or ethylsulfonyloxy.

(76) “Alkenylsulfonyloxy” means a group wherein the above “alkenylsulfonyl” is bonded to an oxygen atom. For example, it includes ethylenylsulfonyloxy, propenylsulfonyloxy and the like.

(77) “Alkynylsulfonyloxy” means a group wherein the above “alkynylsulfonyl” is bonded to an oxygen atom. For example, it includes ethynylsulfonyloxy, propynylsulfonyloxy and the like.

(78) “Alkyloxysulfonyl” means a group wherein the above “alkyloxy” is bonded to a sulfonyl group. For example, it includes methyloxysulfonyl, ethyloxysulfonyl, propyloxysulfonyl, isopropyloxysulfonyl, tert-butyloxysulfonyl, isobutyloxysulfonyl, sec-butyloxysulfonyl, pentyloxysulfonyl, isopentyloxysulfonyl, hexyloxysulfenyl and the like.

(79) A preferred embodiment of “alkyloxysulfonyl” is methyloxysulfonyl, ethyloxysulfonyl, or propyloxysulfonyl.

(80) “Alkenyloxysulfonyl” means a group wherein the above “alkenyloxy” is bonded to a sulfonyl group. For example, it includes ethylenyloxysulfonyl, propenyloxysulfonyl and the like.

(81) “Alkynyloxysulfonyl” means a group wherein the above “alkynyloxy” is bonded to a sulfonyl group. For example, it includes ethynyloxysulfonyl, propynyloxysulfonyl and the like.

(82) “Alkylcarbamoyl” means a group wherein a hydrogen atom bonded to a nitrogen atom of a carbamoyl group is replaced with the above “alkyl”. For example, it includes methylcarbamoyl, ethylcarbamoyl and the like. Another hydrogen atom bonded to the nitrogen atom of the carbamoyl group may be replaced with the above “alkyl”.

(83) “Alkenylcarbamoyl” means a group wherein a hydrogen atom bonded to a nitrogen atom of a carbamoyl group is replaced with the above “alkenyl”. For example, it includes ethylenylcarbamoyl, propenylcarbamoyl and the like. Another hydrogen atom bonded to the nitrogen atom of the carbamoyl group may be replaced with the above “alkyl”.

(84) “Alkynylcarbamoyl” means a group wherein a hydrogen atom bonded to a nitrogen atom of a carbamoyl group is replaced with the above “alkynyl”. For example, it includes ethynylcarbamoyl, propynyl carbamoyl and the like. Another hydrogen atom bonded to the nitrogen atom of the carbamoyl group may be replaced with the above “alkyl”.

(85) “Alkylsulfamoyl” means a group wherein a hydrogen atom bonded to a nitrogen atom of a sulfamoyl group is replaced with the above “alkyl”. For example, it includes methylsulfamoyl, dimethylsulfamoyl and the like. Another hydrogen atom bonded to the nitrogen atom of the sulfamoyl group may be replaced with the above “alkyl”.

(86) “Alkenylsulfamoyl” means a group wherein a hydrogen atom bonded to a nitrogen atom of a sulfamoyl group is replaced with the above “alkenyl”. For example, it includes ethylenylsulfamoyl, propenylsulfamoyl and the like. Another hydrogen atom bonded to the nitrogen atom of the carbamoyl group may be replaced with the above “alkyl”.

(87) “Alkynylsulfamoyl” means a group wherein a hydrogen atom bonded to a nitrogen atom of a sulfamoyl group is replaced with the above “alkynyl”. For example, it includes ethynylsulfamoyl, propynylsulfamoyl and the like. Another hydrogen atom bonded to the nitrogen atom of the carbamoyl group may be replaced with the above “alkyl”.

(88) “Alkylcarbonylamino” means a group wherein a hydrogen atom bonded to a nitrogen atom of an amino group is replaced with the above “alkylcarbonyl”. For example, it includes methylcarbonylamino, ethylcarbonylamino, propylcarbonylamino, isopropylcarbonylamino, tert-butylcarbonylamino, isobutylcarbonylamino, sec-butylcarbonylamino and the like. Another hydrogen atom bonded to the nitrogen atom of the amino group may be replaced with the above “alkyl”.

(89) A preferred embodiment of “alkylcarbonylamino” is methylcarbonylamino or ethylcarbonylamino.

(90) “Alkenylcarbonylamino” means a group wherein a hydrogen atom bonded to a nitrogen atom of an amino group is replaced with the above “alkenylcarbonyl”. For example, it includes ethylenylcarbonylamino, propenylcarbonylamino and the like. Another hydrogen atom bonded to the nitrogen atom of the amino group may be replaced with the above “alkyl”.

(91) “Alkynylcarbonylamino” means a group wherein a hydrogen atom bonded to a nitrogen atom of an amino group is replaced with the above “alkynylcarbonyl”. For example, it includes ethynylcarbonylamino, propynylcarbonylamino and the like. Another hydrogen atom bonded to the nitrogen atom of the amino group may be replaced with the above “alkyl”.

(92) “Alkylsulfonylamino” means a group wherein a hydrogen atom bonded to a nitrogen atom of an amino group is replaced with the above “alkylsulfonyl”. For example, it includes methylsulfonylamino, ethylsulfonylamino, propylsulfonylamino, isopropylsulfonylamino, tert-butylsulfonylamino, isobutylsulfonylamino, sec-butylsulfonylamino and the like. Another hydrogen atom bonded to the nitrogen atom of the amino group may be replaced with the above “alkyl”.

(93) A preferred embodiment, of “alkylsulfonylamino” is methylsulfonylamino or ethylsulfonylamino.

(94) “Alkonylsulfonylamino” means a group wherein a hydrogen atom bonded to a nitrogen atom of an amino group is replaced with the above “alkenylsulfonyl”. For example, it includes ethylenylsulfonylamino, propenylsulfonylamino and the like. Another hydrogen atom bonded to the nitrogen atom of the amino group may be replaced with the above “alkyl”.

(95) “Alkynylsulfonylamino” means a group wherein a hydrogen atom bonded to a nitrogen atom of an amino group is replaced with the above “alkynylsulfonyl”. For example, it includes ethynylsulfonylamino, propynylsulfonylamino and the like. Another hydrogen atom bonded to the nitrogen atom of the amino group may be replaced with the above “alkyl”.

(96) “Alkyloxycarbonylamino” means a group wherein a hydrogen atom bonded to a nitrogen atom of an amino group is replaced with the above “alkyloxycarbonyl”. For example, it includes methyloxycarbonylamino, ethyloxycarbonylamino, propyloxycarbonyl amino, isopropyloxycarbonyl amino, tert-butyloxycarbonylamino, isobutyloxycarbonylamino, sec-butyloxycarbonylamino, pentyloxycarbonylamino, isopentyloxycarbonylamino, hexyloxycarbonylamino and the like. Another hydrogen atom bonded to the nitrogen atom of the amino group may be replaced with the above “alkyl”.

(97) A preferred embodiment of “alkyloxycarbonyl” is methyloxycarbonylamino, ethyloxycarbonylamino, propyloxycarbonylamino and the like.

(98) “Alkenyloxycarbonylamino” means a group wherein a hydrogen atom bonded to a nitrogen atom of an amino group is replaced with the above “alkenyloxycarbonyl”. For example, it includes ethylenyloxycarbonylamino, propenyloxycarbonylamino and the like. Another hydrogen atom bonded to the nitrogen atom of the amino group may be replaced with the above “alkyl”.

(99) “Alkynyloxycarbonylamino” means a group wherein a hydrogen atom bonded to a nitrogen atom of an amino group is replaced with the above “alkynyloxycarbonyl”. For example, it includes ethynyloxycarbonylamino, propynyloxycarbonylamino and the like. Another hydrogen atom bonded to the nitrogen atom of the amino group may be replaced with the above “alkyl”.

(100) “Haloalkyl” moans a group wherein one or more “halogen” described above is bonded to the above “alkyl”. For example, it includes monofluoromethyl, monofluoroethyl, monofluoropropyl, 2,2,3,3,3-pentafluoropropyl, monochloromethyl, trifluoromethyl, trichloromethyl. 2,2,2-trifluoroethyl, 2,2,2-trichloroethyl, 1,2-dibromoethyl, 1,1,1-trifluoropropan-2-yl and the like.

(101) A preferred embodiment, of “haloalkyl” is trifluoromethyl or trichloromethyl.

(102) “Haloalkyloxy” means a group wherein the above “haloalkyl” is bonded to an oxygen atom. For example, it includes monofluoromethoxy, monofluoroethoxy, trifluoromethoxy, trichloromethoxy, trifluoroethoxy, trichloroethoxy and the like.

(103) A preferred embodiment of “haloalkyloxy” is trifluoromethoxy or trichloromethoxy.

(104) “Haloalkylamino” means a group wherein a hydrogen atom bonded to a nitrogen atom of on amino group is replaced with the above “haloalkyl”. For example, it includes monofluoromethyl amino, monofluoroethylamino, trifluoromethylamine, trichloromethylamino, trifluoroethylamino, trichloroethylamine and the like. Another hydrogen atom bonded to the nitrogen atom of the amino group may be replaced with the above “alkyl” or the above “haloalkyl”.

(105) A preferred embodiment of “haloalkylamino” is trifluoromethylamine or trichloromethylamino.

(106) “Haloalkylsulfanyl” means a group wherein the above “haloalkyl” is bonded to a sulfanyl group. For example, it includes monofluoromethylsulfanyl, monofluoroethylsulfanyl, trifluoromethylsulfanyl, trichloromethyl sulfanyl, trifluoroethylsulfonyl, trichloroethylsulfanyl and the like.

(107) A preferred embodiment of “haloalkylsulfanyl” is trifluoromethylsulfanyl or trichloromethylsulfonyl.

(108) “Haloalkylcarbonyl” means a group wherein the above “haloalkyl” is bonded to a carbonyl group. For example, it includes monofluoromothylcarbonyl, monofluoroethylcarbonyl, trifluoromethylcarbonyl, trichloromethylcarbonyl, trifluoroethylcarbonyl, trichloroethylcarbonyl and the like.

(109) A preferred embodiment of “haloalkylcarbonyl” is trifluoromethylcarbonyl or trichloromethylcarbonyl.

(110) “Haloalkylsulfonyl” means a group wherein the above “haloalkyl” is bonded to a sulfonyl group. For example, it includes monofluoromethylsulfonyl, monofluoroethylsulfonyl, trifluoromethylsulfonyl, trichloromethylsulfonyl, trifluoroethylsulfonyl, trichloroethylsulfonyl and the like.

(111) A preferred embodiment of “haloalkylsulfonyl” is trifluoromethylsulfonyl or trichloromethylsulfonyl.

(112) “Haloalkylcarbamoyl” means a group wherein a hydrogen atom bonded to a nitrogen atom of a carbamoyl group is replaced with the above “haloalkyl”. For example, it includes monofluoromethylcarbamoyl, monofluoroethylcarbamoyl, trifluoromethylcarbamoyl, trichloromethylcarbamoyl, trifluoroethylcarbamoyl, trichloroethylcorbamoyl and the like. Another hydrogen atom bonded to the nitrogen atom of the carbamoyl group may be replaced with the above “alkyl” or the above “haloalkyl”.

(113) A preferred embodiment, of “haloalkylcarbamoyl” is trifluoromethylcarbamoyl or trichloromethylcarbamoyl.

(114) “Haloalkylsulfamoyl” means a group wherein a hydrogen atom bonded to a nitrogen atom of a sulfamoyl group is replaced with the above “haloalkyl”. For example, it includes monofluoromethylsulfamoyl, monofluoroethylsulfamoyl, trifluoromethylsulfainoyl, trichloromethylsulfamoyl, trifluo methylsulfamoyl, trichloroethylsulfamoyl and the like. Another hydrogen atom bonded to the nitrogen atom of the sulfamoyl group may be replaced with the above “alkyl” or the above “haloalkyl”.

(115) A preferred embodiment of “haloalkylsulfamoyl” is trifluoromethylsulfamoyl or trichloromethylsulfamoyl.

(116) “Haloalkylcarbonylamino” means a group wherein a hydrogen atom bonded to a nitrogen atom of an amino group is replaced with the above “haloalkylcarbonyl”. For example, it includes monofluoromethylcarbonylamino, monofluoroethylcarbonylamino, trifluoromethylcarbonylamino, trichloromethylcarbonylamino, trifluoroethylcarbonylamino, trichloroethylcarbonylamino and the like. Another hydrogen atom bonded to the nitrogen atom of the amino group may be replaced with the above “alkyl” or the above “haloalkyl”.

(117) A preferred embodiment of “haloalkylcarbonylamino” is trifluoromethylcarbonylamino or trichloromethylcarbonylamino.

(118) “Haloalkylsulfonylamino” means a group wherein a hydrogen atom bonded to a nitrogen atom of an amino group is replaced with the above “haloalkylsulfonyl”. For example, it includes monofluoromethylsulfonylamino, monofluoroethyl sulfonyl amino, trifluoromethylsulfonylamino, trichloromethylsulfonylamino, trifluoroethylsulfonylamino, trichloroethylsulfonylamino and the like. Another hydrogen atom bonded to the nitrogen atom of the amino group may be replaced with the above “alkyl” or the above “haloalkyl”.

(119) A preferred embodiment of “haloalkylsulfonylamino” is trifluoromethylsulfonylamino or trichloromethylsulfonylamino.

(120) The “aromatic carbocycle” part of “aromatic carbocyclyloxy”, “aromatic carbocyclylamino”, “aromatic carbocyclylsulfanyl”, “aromatic carbocyclylcarbonyl”, “aromatic carbocyclylsulfonyl”, “aromatic carbocyclylcarbonyloxy”, “aromatic carbocyclylsulfonyloxy”, “aromatic carbocyclyloxycarbonyl”, “aromatic carbocyclyloxysulfonyl”, “aromatic carbocyclylcarbamoyl”, “aromatic carbocyclylsulfamoyl”, “aromatic carbocyclylcarbonylamino”, “aromatic carbocyclylsulfonylamino”, and “aromatic carbocyclyloxycarbonylamino” is the same as the above “aromatic carbocyclyl”.

(121) “Aromatic carbocyclyloxy” means a group wherein “aromatic carbocycle” is bonded to an oxygen atom. For example, it includes phenyloxy, naphthyloxy and the like.

(122) “Aromatic carbocyclylamino” means a group wherein a hydrogen atom attached to a nitrogen atom of an amino group is replaced with the “aromatic carbocycle”. For example, it includes phenylamino, naphthylamino and the like. Another hydrogen atom bonded to the nitrogen atom of the amino group may be replaced with the above “alkyl”.

(123) “Aromatic carbocyclylsulfanyl” means a group wherein a hydrogen atom bonded to a sulfur atom of a sulfanyl group is replaced with “aromatic carbocycle”. For example, it includes phenylsulfanyl, naphthylsulfanyl and the like.

(124) “Aromatic carbocyclylcarbonyl” means a group wherein “aromatic carbocycle” is bonded to a carbonyl group. For example, it includes phenylcarbonyl, naphthylcarbonyl and the like.

(125) “Aromatic carbocyclylsulfonyl” means a group wherein “aromatic carbocycle” is bonded to a sulfonyl group. For example, it, includes phenylsulfonyl, naphthylsulfonyl and the like.

(126) “Aromatic carbocyclylcarbonyloxy” means a group wherein the above “aromatic carbocyclylcarbonyl” is bonded to an oxygen atom. For example, it includes phenylcarbonyloxy, naphthylcarbonyloxy and the like.

(127) “Aromatic carbocyclylsulfonyloxy” means a group wherein the above “aromatic carbocyclylsulfonyl” is bonded to an oxygen atom. For example, it includes phenylsulfonyloxy, naphthylsulfonyloxy and the like.

(128) “Aromatic carbocyclyloxycarbonyl” means a group wherein the above “aromatic carbocyclyloxy” is bonded to a carbonyl group. For example, it includes phenyloxycarbonyl, naphthyloxycarbonyl and the like.

(129) “Aromatic carbocycyloxysulfonyl” means a group wherein the above “aromatic carbocyclyloxy” is bonded to a sulfonyl group. For example, it includes phenyloxysulfonyl, naphthyloxysulfonyl and the like.

(130) “Aromatic carbocyclylcarbamoyl” means a group wherein a hydrogen atom bonded to a nitrogen atom of a carbamoyl group is replaced with the “aromatic carbocycle”. For example, it includes phenylcarbamoyl, naphthylcarbamoyl and the like. Another hydrogen atom bonded to the nitrogen atom of the carbamoyl group may be replaced with the above “alkyl”.

(131) “Aromatic carbocyclylsulfamoyl” means a group wherein a hydrogen atom bonded to a nitrogen atom of a sulfamoyl group is replaced with the “aromatic carbocycle”. For example, it includes phenylsulfamoyl, naphthylsulfoniyl and the like. Another hydrogen atom bonded to the nitrogen atom of the sulfamoyl group may be replaced with the above “alkyl”.

(132) “Aromatic carbocyclylcarbonylamino” means a group wherein a hydrogen atom attached to a nitrogen atom of an amino group is replaced with the above “aromatic carbocyclylcarbonyl”. For example, it includes phenylcarbonylamino, naphthylcarbonylamino and the like. Another hydrogen atom bonded to the nitrogen atom of the amino group may be replaced with the above “alkyl”.

(133) “Aromatic carbocyclylsulfonylamino” means a group wherein a hydrogen atom bonded to a nitrogen atom of an amino group is replaced with the above “aromatic carbocyclylsulfonyl”. For example, it includes phenylsulfonylamino, naphthylsulfonylamino and the like. Another hydrogen atom bonded to the nitrogen atom of the amino group may be replaced with the above “alkyl”.

(134) “Aromatic carbocyclyloxycarbonylamino” means a group wherein a hydrogen atom attached to a nitrogen atom of an amino group is replaced with the above “aromatic carbocyclyloxycarbonyl”. For example, it includes phenyloxycarbonylamino, naphthyloxycarbonylamino and the like. Another hydrogen atom bonded to the nitrogen atom of the amino group may be replaced with the above “alkyl”.

(135) The “non-aromatic carbocycle” part of “non-aromatic carbocyclyloxy”, “non-aromatic carbocyclylamino”, “non-aromatic carbocyclylsulfanyl”, “non-aromatic carbocyclylcarbonyl”, “non-aromatic carbocyclylsulfonyl”, “non-aromatic carbocyclylcarbonyloxy”, “non-aromatic carbocyclylsulfonyloxy”, “non-aromatic carbocyclyloxycarbonyl”, “non-aromatic carbocyclyloxysulfonyl”, “non-aromatic carbocyclylcarbamoyl”, “non-aromatic carbocyclylsulfamoyl”, “non-aromatic carbocyclylcarbonylamino”, “non-aromatic carbocyclylsulfonylamino”, and “non-aromatic carbocyclyloxycarbonylamino” is the same as the above “non-aromatic carbocyclyl”.

(136) “Non-aromatic carbocyclyloxy” means a group wherein “non-aromatic carbocycle” is bonded to an oxygen atom. For example, it includes cyclopropyloxy, cyclohexyloxy, cyclohexenyloxy and the like.

(137) “Non-aromatic carbocyclylamino” means a group wherein a hydrogen atom attached to a nitrogen atom of an amino group is replaced with the “non-aromatic carbocycle”. For example, it includes cyclopropylamino, cyclohexylamino, cyclohexenylamino and the like. Another hydrogen atom bonded to the nitrogen atom of the amino group may be replaced with the above “alkyl”.

(138) “Non-aromatic carbocyclylsulfanyl” means a group wherein a hydrogen atom bonded to a sulfur atom of a sulfanyl group is replaced with “non-aromatic carbocycle”. For example, it includes cyclopropylsulfanyl, cyclohexylsulfanyl, cyclohexenylsulfanyl and the like.

(139) “Non-aromatic carbocyclylcarbonyl” means a group wherein “non-aromatic carbocycle” is bonded to a carbonyl group. For example, it includes cyclopropylcarbonyl, cyclohexylcarbonyl, cyclohexenylcarbonyl and the like.

(140) “Non-aromatic carbocyclylsulfonyl” means a group wherein “non-aromatic carbocycle” is bonded to a sulfonyl group. For example, it includes cyclopropylsulfonyl, cyclohexylsulfonyl, cyclohexenylsulfonyl and the like.

(141) “Non-aromatic carbocyclylcarbonyloxy” means a group wherein the above “non-aromatic carbocyclylcarbonyl” is bonded to an oxygen atom. For example, it includes cyclopropylcarbonyloxy, cyclohexylcarbonyloxy, cyclohexenylcarbonyloxy and the like.

(142) “Non-aromatic carbocyctylsulfonyloxy” means a group wherein the above “non-aromatic carbocyclylsulfonyl” is bonded to an oxygen atom. For example, it includes cyclopropylsulfonyloxy, cyclohexylsulfonyloxy, cyclohexenylsulfonyloxy and the like.

(143) “Non-aromatic carbocyclyloxycarbonyl” means a group wherein the above “non-aromatic carbocyclyloxy” is bonded to a carbonyl group. For example, it includes cyclopropyloxycarbonyl, cyclohexyloxycarbonyl, cyclohexenyloxycarbonyl and the like.

(144) “Non-aromatic carbocyclyloxyaulfonyl” means a group wherein the above “non-aromatic carbocyclyloxy” is bonded to a sulfonyl group. For example, it includes cyclopropyloxysulfonyl, cyclohexyloxysulfonyl, cyclohexenyloxysulfonyl and the like.

(145) “Non-aromatic carbocyclylcarbamoyl” means a group wherein a hydrogen atom bonded to a nitrogen atom of a carbamoyl group is replaced with the “non-aromatic carbocycle”. For example, it includes cyclopropylcarbamoyl, cyclohexylcarbamoyl, cyclohexenylcarbamoyl and the like. Another hydrogen atom bonded to the nitrogen atom of the carbamoyl group may be replaced with the above “alkyl”.

(146) “Non-aromatic carbocyclylsulfamoyl” means a group wherein a hydrogen atom bonded to a nitrogen atom of a sulfamoyl group is replaced with the “non-aromatic carbocycle”. For example, it includes cyclopropylsulfamoyl, cyclohexylsulfamoyl, cyclohexenylsulfamoyl and the like. Another hydrogen atom bonded to the nitrogen atom of the sulfamoyl group may be replaced with the above “alkyl”.

(147) “Non-aromatic carbocyclylcarbonylamino” means a group wherein a hydrogen atom attached to a nitrogen atom of an amino group is replaced with the above “non-aromatic carbocyclylcarbonyl”. For example, it includes cyclopropylcarbonyl amino, cyclohexylcarbonylamino, cyclohexenylcarbonylamino and the like. Another hydrogen atom bonded to the nitrogen atom of the amino group may be replaced with the above “alkyl”.

(148) “Non-aromatic carbocyclylsulfonylamino” means a group wherein a hydrogen atom bonded to a nitrogen atom of an amino group is replaced with the above “non-aromatic carbocyclylsulfonyl”. For example, it includes cyclopropylsulfonylamino, cyclo hexylsulfonyl amino, cyclohexenylsulfonylamino and the like. Another hydrogen atom bonded to the nitrogen atom of the amino group may be replaced with the above “alkyl”.

(149) “Non-aromatic carbocyclyloxycarbonylamino” means a group wherein a hydrogen atom attached to a nitrogen atom of an amino group is replaced with the above “non-aromatic carbocyclyloxycarbonyl”. For example, it includes cyclopropyloxycarbonylamino, cyclohexyloxycarbonylamino, cyclohexanyloxycarbonyl amino and the like. Another hydrogen atom bonded to the nitrogen atom of the amino group may be replaced with the above “alkyl”.

(150) The “aromatic heterocycle” part of “aromatic heterocyclyloxy”, “aromatic heterocyclylamino”, “aromatic heterocyclylsulfanyl”, “aromatic heterocyclylcarbonyl”, “aromatic heterocyclylsulfonyl”, “aromatic heterocyclylcarbonyloxy”, “aromatic heterocyclylsulfonyloxy”, “aromatic heterocyclyloxycarbonyl”, “aromatic heterocyclyloxysulfonyl”, “aromatic heterocyclylcarbamoyl”, “aromatic heterocyclylsulfamoyl”, “aromatic heterocyclylcarbonylamino”, “aromatic heterocyclylsulfonylamino”, and “aromatic hoterocyclyloxycarbonylamino” is the same as the above “aromatic heterocyclyl”.

(151) “Aromatic heterocyclyloxy” means a group wherein “aromatic heterocycle” is bonded to an oxygen atom. For example, it includes pyridyloxy, oxazolyloxy and the like.

(152) “Aromatic heterocyclylamino” means a group wherein a hydrogen atom attached to a nitrogen atom of an amino group is replaced with the “aromatic heterocycle”. For example, it includes pyridylamino, oxazolylamino and the like. Another hydrogen atom bonded to the nitrogen atom of the amino group may be replaced with the above “alkyl”.

(153) “Aromatic heterocyclylsulfanyl” means a group wherein a hydrogen atom bonded to a sulfur atom of a sulfanyl group is replaced with “aromatic heterocycle”. For example, it includes pyridylsulfanyl, oxazol ylsulfanyl and the like.

(154) “Aromatic heterocyclylcarbonyl” means a group wherein “aromatic heterocycle” is bonded to a carbonyl group. For example, it includes pyridylcarbonyl, oxazolylcarbonyl and the like.

(155) “Aromatic heterocyclylsulfonyl” means a group wherein “aromatic heterocycle” is bonded to a sulfonyl group. For example, it includes pyridylsulfonyl, oxazolylsulfonyl and the like.

(156) “Aromatic heterocyclylcarbonyloxy” means a group wherein the above “aromatic heterocyclylcarbonyl” is bonded to an oxygen atom. For example, it includes pyridylcarbonyloxy, oxazolylcarbonyloxy and the like.

(157) “Aromatic hetorocyclylsulfonyloxy” means a group wherein the above “aromatic heterocyclylsulfonyl” is bonded to an oxygen atom. For example, it includes pyridylsulfonyloxy, oxazolylsulfonyloxy and the like.

(158) “Aromatic heterocyclyloxycarbonyl” means a group wherein the above “aromatic heterocyclyloxy” is bonded to a carbonyl group. For example, it includes pyridyloxycarbonyl, oxazolyloxycarbonyl and the like.

(159) “Aromatic heterocyclyloxysulfonyl” means a group wherein the above “aromatic heterocyclyloxy” is bonded to a sulfonyl group. For example, it includes pyridyloxysulfonyl, oxazolyloxysulfonyl and the like.

(160) “Aromatic heterocyclylcarbamoyl” means a group wherein a hydrogen atom bonded to a nitrogen atom of a carbamoyl group is replaced with the “aromatic heterocycle”. For example, it includes pyridylcarbamoyl, oxazol ylcarbamoyl and the like. Another hydrogen atom bonded to the nitrogen atom of the carbamoyl group may be replaced with the above “alkyl”.

(161) “Aromatic heterocycylsulfamoyl” means a group wherein a hydrogen atom bonded to a nitrogen atom of a sulfamoyl group is replaced with the “aromatic heterocycle”. For example, it includes pyridylsulfamoyl, oxazolylsulfamoyl and the like. Another hydrogen atom bonded to the nitrogen atom of the sulfamoyl group may be replaced with the above “alkyl”.

(162) “Aromatic heterocyclylcarbonyl amino” means a group wherein a hydrogen atom attached to a nitrogen atom of an amino group is replaced with the above “aromatic heterocyclylcarbonyl”. For example, it includes pyridylcarbonylamino, oxazolylcarbonylamino and the like. Another hydrogen atom bonded to the nitrogen atom of the amino group may be replaced with the above “alkyl”.

(163) “Aromatic heterocyclylsulfonylamino” means a group wherein a hydrogen atom bonded to a nitrogen atom of an amino group is replaced with the above “aromatic heterocyclylsulfonyl”. For example, it includes pyridylsulfonylamino, oxazolylsulfonylamino and the like. Another hydrogen atom bonded to the nitrogen atom of the amino group may be replaced with the above “alkyl”.

(164) “Aromatic heterocyclyloxycarbonylamino” means a group wherein a hydrogen atom attached to a nitrogen atom of an amino group is replaced with the above “aromatic heterocyclyloxycarbonyl”. For example, it includes pyridyloxycarbonylamino, oxazolyloxycarbonylamino and the like. Another hydrogen atom bonded to the nitrogen atom of the amino group may be replaced with the above “alkyl”.

(165) The “non-aromatic heterocycle” part of “non-aromatic heterocyclyloxy”, “non-aromatic heterocyclylamino”, “non-aromatic heterocyclyl sulfanyl”, “non-aromatic heterocyclylcarbonyl”, “non-aromatic heterocyclylsulfonyl”, “non-aromatic heterocyclylcarbonyloxy”, “non-aromatic heterocyclylsulfonyloxy”, “non-aromatic heterocyclyloxycarbonyl”, “non-aromatic heterocyclyloxysulfonyl”, “non-aromatic heterocyclylcarbamoyl”, “non-aromatic heterocyclylsulfamoyl”, “non-aromatic heterocyclylcarbonylamino”, “non-aromatic heterocyclylsulfonylamino”, and “non-aromatic heterocyclyloxycarbonylamino” is the same as the above “non-aromatic heterocyclyl”.

(166) “Non-aromatic heterocyclyloxy” means a group wherein “non-aromatic heterocycle” is bonded to an oxygen atom. For example, it includes piperidinyloxy, tetrahydrofuryloxy and the like.

(167) “Non-aromatic heterocyclylamino” means a group wherein a hydrogen atom attached to a nitrogen atom of an amino group is replaced with the “non-aromatic heterocycle”. For example, it includes piperidinylamino, tetrahydrofurylamino and the like. Another hydrogen atom bonded to the nitrogen atom of the amino group may be replaced with the above “alkyl”.

(168) “Non-aromatic heterocyclylsulfanyl” means a group wherein a hydrogen atom bonded to a sulfur atom of a sulfanyl group is replaced with “non-aromatic heterocycle”. For example, it includes piperidinylsulfonyl, tetrahydrofurylsulfanyl and the like.

(169) “Non-aromatic heterocyclylcarbonyl” means a group wherein “non-aromatic heterocycle” is bonded to a carbonyl group. For example, it includes piperidinylcarbonyl, tetrahydrofurylcarbonyl and the like.

(170) “Non-aromatic heterocyclylsulfonyl” means a group wherein “non-aromatic heterocycle” is bonded to a sulfonyl group. For example, it includes piperidinylsulfonyl, tetrahydrofurylsulfonyl and the like.

(171) “Non-aromatic hoterocyclylcarbonyloxy” moans a group wherein the above “non-aromatic heterocyclylcarbonyl” is bonded to an oxygen atom. For example, it includes piperidinylcarbonyloxy, tetrahydrofurylcarbonyloxy and the like.

(172) “Non-aromatic heterocyclylsulfonyloxy” moans a group wherein the above “non-aromatic heterocyclylsulfonyl” is bonded to an oxygen atom. For example, it includes piperidinylsulfonyloxy, tetrahydrofuryl sulfonyloxy and the like.

(173) “Non-aromatic heterocyclyloxycarbonyl” means a group wherein the above “non-aromatic heterocyclyloxy” is bonded to a carbonyl group. For example, it includes piperidinyloxycarbonyl, tetrahydrofuryloxycarbonyl and the like.

(174) “Non-aromatic heterocyclyloxysulfonyl” means a group wherein the above “non-aromatic heterocyclyloxy” is bonded to a sulfonyl group. For example, it includes piperidinyloxysulfonyl, tetrahydrofuryloxysulfonyl and the like.

(175) “Non-aromatic heterocyclylcarbamoyl” means a group wherein a hydrogen atom bonded to a nitrogen atom of a carbamoyl group is replaced with the “non-aromatic heterocycle”. For example, it includes piperidinylcarbamoyl, tetrahydrofurylcarbamoyl and the like. Another hydrogen atom bonded to the nitrogen atom of the carbamoyl group may be replaced with the above “alkyl”.

(176) “Non-aromatic heterocyclylsulfamoyl” means a group wherein a hydrogen atom bonded to a nitrogen atom of a sulfamoyl group is replaced with the “non-aromatic heterocycle”. For example, it includes piperidinylsulfamoyl, tetrahydrofurylsulfamoyl and the like. Another hydrogen atom bonded to the nitrogen atom of the sulfamoyl group may be replaced with the above “alkyl”.

(177) “Non-aromatic heterocyclylcarbonylamino” means a group wherein a hydrogen atom attached to a nitrogen atom of an amino group is replaced with the above “non-aromatic heterocyclylcarbonyl”. For example, it includes piperidinylcarbonylamino, tetrahydrofurylcarbonylamiuo and the like. Another hydrogen atom bonded to the nitrogen atom of the amino group may be replaced with the above “alkyl”.

(178) “Non-aromatic heterocyclylsulfonylamino” means a group wherein a hydrogen atom bonded to a nitrogen atom of an amino group is replaced with the above “non-aromatic heterocyclylsulfonyl”. For example, it includes piperidinylsulfonylamino, tetrahydrofurylsulfonylamino and the like. Another hydrogen atom bonded to the nitrogen atom of the amino group may be replaced with the above “alkyl”.

(179) “Non-aromatic heterocyclyloxycarbonyl amino” means a group wherein a hydrogen atom attached to a nitrogen atom of an amino group is replaced with the above “non-aromatic heterocyclyloxycarbonyl”. For example, it includes piperidinyloxycarbonylamino, tetrahydrofuryloxycarbonylamino and the like. Another hydrogen atom bonded to the nitrogen atom of the amino group may be replaced with the above “alkyl”.

(180) “Haloalkyl” means a group wherein one or more “halogen” described above is bonded to the above “alkyl”. For example, it includes monofluoromethyl, monofluoroethyl, monofluoropropyl, 2,2,3,3,3-pentafluoropropyl, monochloromethyl, trifluoromethyl, trichloromethyl, 2,2,2-trifluoroethyl, 2,2,2-trichloroethyl, 1,2-dibromoethyl, 1,1,1-trifluoropropan-2-yl and the like.

(181) A preferred embodiment of “haloalkyl” is trifluoromethyl or trichloromethyl.

(182) “Haloalkyloxy” means a group wherein the above “haloalkyl” is bonded to an oxygen atom. For example, it includes monofluoromethoxy, Monofluoroethoxy, trifluoromethoxy, trichloromethoxy, trifluoroethoxy, trichloroethoxy and the like.

(183) A preferred embodiment of “halonlkyloxy” is trifluoromethoxy or trichloromethoxy.

(184) “Haloalkylamino” moans a group wherein a hydrogen atom bonded to a nitrogen atom of an amino group is replaced with the above “haloalkyl”, For example, it includes monofluoromethylamino, monofluoroethylamino, trifluoromethylamine, trichloromethylamino, trifluoroethylamino, trichloroethylamine and the like. Another hydrogen atom bonded to the nitrogen atom of the amino group may be replaced with the above “alkyl” or the above “haloalkyl”.

(185) A preferred embodiment of “haloalkylamino” is trifluoromethyl amino or trichloromethylamino.

(186) “Haloalkylsulfonyl” means a group wherein the above “haloalkyl” is bonded to a sulfanyl group. For example, it includes monofluoromethyl sulfanyl, monofluoroethylsulfanyl, trifluoromethylsulfanyl, trichloromethylsulfonyl, trifluoroethylsulfonyl, trichloroethylsulfanyl and the like.

(187) A preferred embodiment of “haloalkylsulfanyl” is trifluoromethylsulfanyl or trichloromethylsulfanyl.

(188) “Haloalkylcarbonyl” means a group wherein the above “haloalkyl” is bonded to a carbonyl group. For example, it includes monofluoromethylcarbonyl, monofluoroethylcarbonyl, trifluoromethylcarbonyl, trichloromethylcarbonyl, trifluoroethylcarbonyl, trichloroethylcarbonyl and the like.

(189) A preferred embodiment of “haloalkylcarbonyl” is trifluoromethylcarbonyl or trichloromethylcarbonyl.

(190) “Haloalkylsulfonyl” means a group wherein the above “haloalkyl” is bonded to a sulfonyl group. For example, it includes monofluoromethylsulfonyl, monofluoroethylsulfonyl, trifluoromethylsulfonyl, trichloromethylsulfonyl, trifluoroethylsulfonyl, trichloroethyl sulfonyl and the like.

(191) A preferred embodiment of “haloalkylsulfonyl” is trifluoromethylsulfonyl or trichloromethylsulfonyl.

(192) “Haloalkylcorbamoyl” means a group wherein a hydrogen atom bonded to a nitrogen atom of a carbamoyl group is replaced with the above “haloalkyl”. For example, it includes monofluoromethylcarbamoyl, monofluoroethylcarbamoyl, trifluoromethylcarbamoyl, trichloromethylcarbamoyl, trifluoroethylcarbamoyl, trichloroethylcarbamoyl and the like. Another hydrogen atom bonded to the nitrogen atom of the carbamoyl group may be replaced with the above “alkyl” or the above “haloalkyl”.

(193) A preferred embodiment of “haloalkylcarbamoyl” is trifluoromethylcarbamoyl or trichloromethylcarbamoyl.

(194) “Haloalkylsulfamoyl” means a group wherein a hydrogen atom bonded to a nitrogen atom of a sulfamoyl group is replaced with the above “haloalkyl”. For example, it includes monofluoromethylsulfamoyl, monofluoroethylsulfamoyl, trifluoromethylsulfamoyl, trichloromethylsulfamoyl, trifluoroethylsulfamoyl, trichloroethylsulfamoyl and the like. Another hydrogen atom bonded to the nitrogen atom of the sulfamoyl group may be replaced with the above “alkyl” or the above “haloalkyl”.

(195) A preferred embodiment of “haloalkylsulfamoyl” is trifluoromethylsulfamoyl or trichloromethylsulfamoyl.

(196) “Haloalkylcarbonylamino” means a group wherein a hydrogen atom bonded to a nitrogen atom of an amino group is replaced with the above “haloalkylcarbonyl”. For example, it includes monofluoromethylcarbonylamino, monofluoroethylcarbonylamino, trifluoromethylcarbonylamino, trichloromethylcarbonylamino, trifluoroethylcarbonylamino, trichloroethylcarbonylamino and the like. Another hydrogen atom bonded to the nitrogen atom of the amino group may be replaced with the above “alkyl” or the above “haloalkyl”.

(197) A preferred embodiment of “haloalkylcarbonylamino” is trifluoromethylcarbonylamino or trichloromethylcarbonylamino.

(198) “Haloalkylsulfonylamino” means a group wherein a hydrogen atom bonded to a nitrogen atom of an amino group is replaced with the above “haloalkylsulfonyl”. For example, it includes monofluoromethylsulfonylamino, monofluoroethylsulfonylamino, trifluoromethylsulfonylamino, trichloromethylsulfonylamino, trifluoroethylsulfonylamino, trichloroethylsulfonylamino and the like. Another hydrogen atom bonded to the nitrogen atom of the amino group may be replaced with the above “alkyl” or the above “haloalkyl”.

(199) A preferred embodiment of “haloalkylsulfonylamino” is trifluoromethylsulfonylamino or trichloromethylsulfonylamino.

(200) “Haloalkylcarbonyloxy” means a group wherein the above “haloalkylcarbonyl” is bonded to an oxygen atom. For example, it includes monofluoromethylcarbonyloxy, monofluoroethylcarbonyloxy, trifluoromethylcarbonyloxy, (trichloromethylcarbonyloxy, trifluoroethylcarbonyloxy, trichloroethylcarbonyloxy and the like.

(201) A preferred embodiment of “haloalkylcarbonyloxy” is trifluoromethylcarbonyloxy or trichloromethylcarbonyloxy.

(202) “Haloalkylsulfonyloxy” means a group wherein the above “haloalkylsulfonyl” is bonded to an oxygen atom. For example, it includes monofluoromethylsulfonyloxy, monofluoroetliylsulfonyloxy, trifluoromethylsulfonyloxy, trichloromethyl sulfonyloxy, trifluoroethylsulfonyloxy, trichloroethylsulfonyloxy and the like.

(203) A preferred embodiment of “haloalkylsulfonyloxy” is trifluoromethylsulfonyloxy or trichloromethylsulfonyloxy.

(204) “Haloalkyloxycarbonyl” means a group wherein the above “haloaryloxy” is bonded to a carbonyl group. For example, it includes monofluoromethyl oxycarbonyl, monofluoroethyloxycarbonyl, trifluoromethyloxycarbonyl, trichloromethyloxycarbonyl, trifluoroethyloxycarbonyl, trichloroethyloxycarbonyl and the like.

(205) A preferred embodiment of “haloalkyloxycarbonyl” is trifluoromethyloxycarbonyl or trichloromethyloxycarbonyl.

(206) “Haloalkyloxysulfonyl” means a group wherein the above “haloaryloxy” is bonded to a sulfonyl group. For example, it includes monofluoromethyloxysulfonyl, monofluoroethyloxysulfonyl, trifluoromethyl oxysulfonyl, trichloromethyloxy sulfonyl, trifluoroethyloxysulfonyl, trichloroethyloxysulfonyl and the like.

(207) A preferred embodiment of “haloalkyloxysulfonyl” is trifluoromethyl oxysulfonyl or trichloromethyloxysulfonyl.

(208) The substituents of “substituted or unsubstituted alkyl” include the substituent group A. A carbon atom at any position(s) may be bonded to one or more group(s) selected from the substituent group A.

(209) The substituent group A: halogen, hydroxy, carboxy, amino, carbamoyl, sulfamoyl, sulfo, cyano, alkyloxy optionally substituted with one or more group(s) selected from the substituent group C, alkylamino optionally substituted with one or more group(s) selected from the substituent group C, alkylsulfanyl optionally substituted with one or more group(s) selected from the substituent group C, alkylcarbonyl optionally substituted with one or more group(s) selected from the substituent, group C, alkylsulfonyl optionally substituted with one or more group(s) selected from the substituent group C, alkylcarbonylamino optionally substituted with one or more group(s) selected from the substituent, group C, alkylsulfonylamino optionally substituted with one or more group(s) selected from the substituent group C, alkylcarbamoyl optionally substituted with one or more group(s) selected from the substituent group C, alkylsulfamoyl optionally substituted with one or more group(s) selected from the substituent group C, alkylcarbonyloxy optionally substituted with one or more group(s) selected from the substituent group C, alkyloxycarbonyl optionally substituted with one or more group(s) selected from the substituent group C, alkylsulfonyloxy optionally substituted with one or more group(s) selected from the substituent group C, aryloxysulfonyl optionally substituted with one or more group(s) selected from the substituent group C, aromatic carbocyclyl optionally substituted with one or more group(s) selected from the substituent group E, non-aromatic carbocyclyl optionally substituted with one or more group(s) selected from the substituent group E, aromatic heterocyclyl optionally substituted with one or more group(s) selected from the substituent group E, non-aromatic heterocyclyl optionally substituted with one or more group(s) selected from the substituent group E, aromatic carbocyclyloxy optionally substituted with one or more group(s) selected from the substituent group E, non-aromatic carbocyclyloxy optionally substituted with one or more group(s) selected from the substituent group E, aromatic heterocyclyloxy optionally substituted with one or more group(s) selected from the substituent group E, non-aromatic heterocyclyloxy optionally substituted with one or more group(s) selected from the substituent group E, aromatic carbocyclylsulfanyl optionally substituted with one or more group(s) selected from the substituent, group E, non-aromatic carbocyclylsulfanyl optionally substituted with one or more group(s) selected from the substituent group E, aromatic heterocyclylsulfanyl optionally substituted with one or more group(s) selected from the substituent group E, non-aromatic heterocyclylsulfanyl optionally substituted with one or more group(s) selected from the substituent group E, aromatic carbocyclylamino optionally substituted with one or more group(s) selected from the substituent group E, non-aromatic carbocyclylamino optionally substituted with one or more group(s) selected from the substituent group E, aromatic heterocyclylamino optionally substituted with one or more group(s) selected from the substituent group E, non-aromatic heterocyclylamino optionally substituted with one or more group(s) selected from the substituent group E, aromatic carbocyclylcarbonyl optionally substituted with one or more group(s) selected from the substituent group E, non-aromatic carbocyclylcarbonyl optionally substituted with one or more group(s) selected from the substituent group E, aromatic heterocyclylcarbonyl optionally substituted with one or more group(s) selected from the substituent group E, non-aromatic heterocyclylcarbonyl optionally substituted with one or more group(s) selected from the substituent group E, aromatic carbocyclylsulfonyl optionally substituted with one or more group(s) selected from the substituent group E, non-aromatic carbocyclylsulfonyl optionally substituted with one or more group(s) selected from the substituent group E, aromatic heterocyclylsulfonyl optionally substituted with one or more group(s) selected from the substituent group E, non-aromatic heterocyclylsulfonyl optionally substituted with one or more group(s) selected from the substituent group E, aromatic carbocyclylcarbonylamino optionally substituted with one or more group(s) selected from the substituent group E, non-aromatic carbocyclylcarbonylamino optionally substituted with one or more group(s) selected from the substituent group E, aromatic heterocyclylcarbonylamino optionally substituted with one or more group(s) selected from the substituent group E, non-aromatic heterocyclylcarbonylamino optionally substituted with one or more group(s) selected from the substituent group E, aromatic carbocyclylsulfonylamino optionally substituted with one or more group(s) selected from the substituent group E, non-aromatic carbocyclylsulfonylamino optionally substituted with one or more groups) selected from the substituent group E, aromatic heterocyclylsulfonylamino optionally substituted with one or more group(s) selected from the substituent group E, non-aromatic heterocyclylsulfonylamino optionally substituted with one or more group(s) selected from the substituent group E, aromatic carbocyclylcarbamoyl optionally substituted with one or more group(s) selected from the substituent group E, non-aromatic carbocyclylcarbamoyl optionally substituted with one or more group(s) selected from the substituent group E, aromatic heterocyclylcarbamoyl optionally substituted with one or more group(s) selected from the substituent group E, non-aromatic heterocyclylcarbamoyl optionally substituted with one or more group(s) selected from the substituent group E, aromatic carbocyclylsulfamoyl optionally substituted with one or more group(s) selected from the substituent group E, non-aromatic carbocyclylsulfamoyl optionally substituted with one or more group(s) selected from the substituent group E, aromatic heterocyclylsulfamoyl optionally substituted with one or more group(s) selected from the substituent group E, non-aromatic heterocyclylsulfamoyl optionally substituted with one or more group(s) selected from the substituent group E, aromatic carbocycyloxycarbonyl optionally substituted with one or more group(s) selected from the substituent group E, non-aromatic carbocyclyloxycarbonyl optionally substituted with one or more group(s) selected from the substituent, group E, aromatic heterocyclyloxycarbonyl optionally substituted with one or more group(s) selected from the substituent group E, non-aromatic heterocyclyloxycarbonyl optionally substituted with one or more group(s) selected from the substituent group E, aromatic carbocyclyloxysulfonyl optionally substituted with one or more group(s) selected from the substituent group E, non-aromatic carbocyclyloxysulfonyl optionally substituted with one or more group(s) selected from the substituent group E, aromatic heterocyclyloxysulfonyl optionally substituted with one or more group(s) selected from the substituent group E, non-aromatic heterocyclyloxysulfonyl optionally substituted with one or more group(s) selected from the substituent group E, aromatic carbocyclylcarbonyloxy optionally substituted with one or more group(s) selected from the substituent group E, non-aromatic carbocyclylcarbonyloxy optionally substituted with one or more group(s) selected from the substituent group E, aromatic heterocyclylcarbonyloxy optionally substituted with one or more group(s) selected from the substituent group E, non-aromatic heterocyclylcarbonyloxy optionally substituted with one or more group(s) selected from the substituent group E, aromatic carbocyclylsulfonyloxy optionally substituted with one or more group(s) selected from the substituent group E, non-aromatic carbocyclylsulfonyloxy optionally substituted with one or more group(s) selected from the substituent group E, aromatic heterocyclylsulfonyloxy optionally substituted with one or more group(s) selected from the substituent, group E, and non-aromatic heterocyclylsulfonyloxy optionally substituted with one or more group(s) selected from the substituent group E.

(210) The substituents of “substituted or unsubstituted alkenyl”, “substituted or unsubstituted alkynyl”, “substituted or unsubstituted alkyloxy”, “substituted or unsubstituted alkenyloxy”, “substituted or unsubstituted alkynyloxy”, “substituted or unsubstituted alkylsulfanyl”, “substituted or unsubstituted alkenylsulfonyl”, “substituted or unsubstituted alkynylsulfanyl”, “substituted or unsubstituted alkylamino”, “substituted or unsubstituted alkenylamino”, “substituted or unsubstituted alkynylamino”, “substituted or unsubstituted alkylcarbonyl”, “substituted or unsubstituted alkenylcarbonyl”, “substituted or unsubstituted alkynylcarbonyl”, “substituted or unsubstituted alkylsulfonyl”, “substituted or unsubstituted alkenylsulfonyl”, “substituted or unsubstituted alkynylsulfonyl”, “substituted or unsubstituted alkylcarbonyloxy”, “substituted or unsubstituted alkenylcarbonyloxy”, “substituted or unsubstituted alkynylcarbonyloxy”, “substituted or unsubstituted alkyloxycarbonyl”, “substituted or unsubstituted alkenyloxycarbonyl”, “substituted or unsubstituted alkynyloxycarbonyl”, “substituted or unsubstituted alkylsulfonyloxy”, “substituted or unsubstituted alkenylsulfonyloxy”, “substituted or unsubstituted alkynylsulfonyloxy”, “substituted or unsubstituted aryloxysulfonyl”, “substituted or unsubstituted alkenyloxysulfonyl”, “substituted or unsubstituted alkynyloxysulfonyl”, “substituted or unsubstituted alkylcarbamoyl”, “substituted or unsubstituted nonylcarbamoyl”, “substituted or unsubstituted alkynylcarbamoyl”, “substituted or unsubstituted alkylsulfamoyl”, “substituted or unsubstituted alkenylsulfamoyl”, “substituted or unsubstituted alkynylsulfamoyl”, “substituted or unsubstituted alkylcarbonylamino”, “substituted or unsubstituted alkenylcarbonylamino”, “substituted or unsubstituted alkynylcarbonylamino”, “substituted or unsubstituted alkylsulfonylamino”, “substituted or unsubstituted alkenylsulfonylamino”, “substituted or unsubstituted alkyloxycarbonylamino”, “substituted or unsubstituted alkenyloxycarbonylamino”, and “substituted or unsubstituted alkynyloxycarbonylamino” include the substituent group B. A carbon atom at arty position(s) may be bonded to one or more group(s) selected from the substituent group B.

(211) The substituent group B: halogen, hydroxy, carboxy, amino, carbamoyl, sulfamoyl, sulfo, cyano, alkyloxy optionally substituted with one or more group(s) selected from the substituent group D, alkylamino optionally substituted with one or more group(s) selected from the substituent group D, alkylsulfanyl optionally substituted with one or more group(s) selected from the substituent group D, alkylcarbonyl optionally substituted with one or more group(s) selected from the substituent group B, alkylsulfonyl optionally substituted with one or more group(s) selected from the substituent group D, alkylcarbonylamino optionally substituted with one or more group(s) selected from the substituent group D, alkylsulfonylamino optionally substituted with one or more group(s) selected from the substituent group D, alkylcarbamoyl optionally substituted with one or more group(s) selected from the substituent group D, alkylsulfamoyl optionally substituted with one or more group (a) selected from the substituent group D, alkylcarbonyloxy optionally substituted with one or more group(s) selected from the substituent group D, alkyloxycarbonyl optionally substituted with one or more group(s) selected from the substituent group D, alkylsulfonyloxy optionally substituted with one or more group(s) selected from the substituent group D, aryloxysulfonyl optionally substituted with one or more group(s) selected from the substituent group D, aromatic carbocyclyl optionally substituted with one or more group(s) selected from the substituent group E, non-aromatic carbocyclyl optionally substituted with one or more group(s) selected from the substituent group E, aromatic heterocyclyl optionally substituted with one or more group(s) selected from the substituent group E, non-aromatic heterocyclyl optionally substituted with one or more group(s) selected from the substituent, group E, aromatic carbocyclyloxy optionally substituted with one or more group(s) selected from the substituent group E, non-aromatic carbocyclyloxy optionally substituted with one or more group(s) selected from the substituent, group E, aromatic heterocyclyloxy optionally substituted with one or more group(s) selected from the substituent group E, non-aromatic heterocyclyloxy optionally substituted with one or more group(s) selected from the substituent group E, aromatic carbocyclylsulfanyl optionally substituted with one or more group(s) selected from the substituent group E, non-aromatic carbocyclylsulfanyl optionally substituted with one or more group(s) selected from the substituent group E, aromatic heterocyclylsulfanyl optionally substituted with one or more group(s) selected from the substituent group E, non-aromatic heterocyclylsulfanyl optionally substituted with one or more group(s) selected from the substituent group E, aromatic carbocyclylamino optionally substituted with one or more group(s) selected from the substituent group E, non-aromatic carbocyclylamino optionally substituted with one or more group(s) selected from the substituent group E, aromatic heterocyclylamino optionally substituted with one or more group(s) selected from the substituent group E, non-aromatic heterocyclylamino optionally substituted with one or more group(s) selected from the substituent group E, aromatic carbocyclylcarbonyl optionally substituted with one or more group (a) selected from the substituent group E, non-aromatic carbocyclylcarbonyl optionally substituted with one or more group(s) selected from the substituent group E, aromatic heterocyclylcarbonyl optionally substituted with one or more group(s) selected from the substituent group E, non-aromatic heterocyclylcarbonyl optionally substituted with one or more group(s) selected from the substituent group E, aromatic carbocyclyl sulfonyl optionally substituted with one or more group(s) selected from the substituent group E, non-aromatic carbocyclylsulfonyl optionally substituted with one or more group(s) selected from the substituent group E, aromatic heterocyclylsulfonyl optionally substituted with one or more group(s) selected from the substituent group E, non-aromatic heterocyclylsulfonyl optionally substituted with one or more group(s) selected from the substituent group E, aromatic carbocyclylcarbonylamino optionally substituted with one or more group(s) selected from the substituent, group E, non-aromatic carbocyclylcarbonylamino optionally substituted with one or more group(s) selected from the substituent group E, aromatic heterocyclylcarbonylamino optionally substituted with one or more group(s) selected from the substituent group E, non-aromatic heterocyclylcarbonylamino optionally substituted with one or more group(s) selected from the substituent group E, aromatic carbocyclylsulfonylamino optionally substituted with one or more group(s) selected from the substituent group E, non-aromatic carbocyclylsulfonylamino optionally substituted with one or more group(s) selected from the substituent group E, aromatic heterocyclylsulfonylamino optionally substituted with one or more group(s) selected from the substituent group E, non-aromatic heterocyclylsulfonylamino optionally substituted with one or more group(s) selected from the substituent group E, aromatic carbocyclylcarbamoyl optionally substituted with one or more group(s) selected from the substituent, group E, non-aromatic carbocyclylcarbamoyl optionally substituted with one or more group(s) selected from the substituent group E, aromatic heterocyclylcarbamoyl optionally substituted with one or more group(s) selected from the substituent group E, non-aromatic heterocyclylcarbamoyl optionally substituted with one or more group(s) selected from the substituent group E, aromatic carbocyclylsulfamoyl optionally substituted with one or more group(s) selected from the substituent group E, non-aromatic carbocyclylsulfamoyl optionally substituted with one or more group(s) selected from the substituent group E, aromatic heterocyclylsulfamoyl optionally substituted with one or more group(s) selected from the substituent group E, non-aromatic heterocyclylsulfamoyl optionally substituted with one or more group(s) selected from the substituent group E, aromatic carbocyclyloxycarbonyl optionally substituted with one or more group(s) selected from the substituent group E, non-aromatic carbocyclyloxycarbonyl optionally substituted with one or more group(s) selected from the substituent group E, aromatic heterocyclyloxycarbonyl optionally substituted with one or more group(s) selected from the substituent group E, non-aromatic heterocyclyloxycarbonyl optionally substituted with one or more group(s) selected from the substituent group E, aromatic carbocyclyloxysulfonyl optionally substituted with one or more group(s) selected from the substituent group E, non-aromatic carbocyclyloxysulfonyl optionally substituted with one or more group(s) selected from the substituent group E, aromatic heterocyclyloxysulfonyl optionally substituted with one or more group(s) selected from the substituent group E, non-aromatic heterocyclyloxysulfonyl optionally substituted with one or more group(s) selected from the substituent group E, aromatic carbocyclylcarbonyloxy optionally substituted with one or more group(s) selected from the substituent group E, non-aromatic carbocyclylcarbonyloxy optionally substituted with one or more group(s) selected from the substituent group E, aromatic heterocyclyl carbonyloxy optionally substituted with one or more group(s) selected from the substituent group E, non-aromatic heterocyclylcarbonyloxy optionally substituted with one or more group(s) selected from the substituent group E, aromatic carbocyclyl sulfonyloxy optionally substituted with one or more group(s) selected from the substituent group E, non-aromatic carbocyclylsulfonyloxy optionally substituted with one or more group(s) selected from the substituent group E, aromatic heterocyclylsulfonyloxy optionally substituted with one or more group(s) selected from the substituent group E, and non-aromatic heterocyclylsulfonyloxy optionally substituted with one or more group(s) selected from the substituent group E.

(212) The substituents on the rings of “aromatic carbocycle”, “non-aromatic carbocycle”, “aromatic heterocycle”, and “non-aromatic heterocycle” of

(213) “substituted or unsubstituted aromatic carbocycle”, “substituted or unsubstituted non-aromatic carbocycle”, “substituted or unsubstituted aromatic heterocycle”, and “substituted or unsubstituted non-aromatic heterocycle”,

(214) “substituted or unsubstituted 6-membered aromatic carbocycle”, “substituted or unsubstituted 5- to 6-membered non-aromatic carbocycle”, “substituted or unsubstituted 5- to 6-membered aromatic heterocycle”, and “substituted or unsubstituted 5- to 6-membered non-aromatic heterocycle”.
“substituted or unsubstituted aromatic carbocyclyl”, “substituted or unsubstituted non-aromatic carbocyclyl”, “substituted or unsubstituted aromatic heterocyclyl”, and “substituted or unsubstituted non-aromatic heterocyclyl”,
“substituted or unsubstituted 6- to 10-membered aromatic carbocyclyl”, “substituted or unsubstituted 3- to 10-membered non-aromatic carbocyclyl”, “substituted or unsubstituted 5- to 10-membered aromatic heterocyclyl”, and “substituted or unsubstituted 3- to 10-membered non-aromatic heterocyclyl”,
“substituted or unsubstituted 6-membered aromatic carbocyclyl”, “substituted or unsubstituted 3- to 6-membered non-aromatic carbocyclyl”, “substituted or unsubstituted 5- to 6-membered aromatic heterocyclyl”, and “substituted or unsubstituted 5- to 6-membered non-aromatic heterocyclyl”,
“substituted or unsubstituted aromatic carbocyclyl”, “substituted or unsubstituted non-aromatic carbocyclyl”, “substituted or unsubstituted aromatic heterocyclyl”, and “substituted or unsubstituted non-aromatic heterocyclyl”,
“substituted or unsubstituted aromatic carbocyclyloxy”, “substituted or unsubstituted non-aromatic carbocyclyloxy”, “substituted or unsubstituted aromatic heterocyclyloxy”, and “substituted or unsubstituted non-aromatic heterocyclyloxy”, “substituted or unsubstituted aromatic carbocyclylamino”, “substituted or unsubstituted non-aromatic carbocyclylamino”, “substituted or unsubstituted aromatic heterocyclylamino”, and “substituted or unsubstituted non-aromatic heterocyclylamino”,
“substituted or unsubstituted aromatic carbocyclylsulfanyl”, “substituted or unsubstituted non-aromatic carbocyclylsulfanyl”, “substituted or unsubstituted aromatic heterocyclylsulfanyl”, and “substituted or unsubstituted non-aromatic heterocyclyl sulfanyl”,
“substituted or unsubstituted aromatic carbocyclylcarbonyl”, “substituted or unsubstituted non-aromatic carbocyclylcarbonyl”, “substituted or unsubstituted aromatic heterocyclylcarbonyl”, and “substituted or unsubstituted non-aromatic heterocyclylcarbonyl”,
“substituted or unsubstituted aromatic carbocyclylsulfonyl”, “substituted or unsubstituted non-aromatic carbocyclylsulfonyl”, “substituted or unsubstituted aromatic heterocyclylsulfonyl”, and “substituted or unsubstituted non-aromatic heterocyclylsulfonyl”,
“substituted or unsubstituted aromatic carbocyclylcarbonyloxy”, “substituted or unsubstituted non-aromatic carbocyclylcarbonyloxy”, “substituted or unsubstituted aromatic heterocyclylcarbonyloxy”, and “substituted or unsubstituted non-aromatic heterocyclylcarbonyloxy”,
“substituted or unsubstituted aromatic carbocyclyloxycarbonyl”, “substituted or unsubstituted non-aromatic carbocyclyloxycarbonyl”, “substituted or unsubstituted aromatic heterocyclyloxycarbonyl”, and “substituted or unsubstituted non-aromatic heterocyclyloxycarbonyl”,
“substituted or unsubstituted aromatic carbocyclylsulfonyloxy”, “substituted or unsubstituted non-aromatic carbocyclylsulfonyloxy”, “substituted or unsubstituted aromatic heterocyclylsulfonyloxy”, and “substituted or unsubstituted non-aromatic haterocyclylsulfonyloxy”,
“substituted or unsubstituted aromatic carbocyclyloxysulfonyl”, “substituted or unsubstituted non-aromatic carbocyclyloxy sulfonyl”, “substituted or unsubstituted aromatic heterocyclyloxysulfonyl”, and “substituted or unsubstituted non-aromatic heterocyclyloxysulfonyl”,
“substituted or unsubstituted aromatic carbocyclylcarbamoyl”, “substituted or unsubstituted non-aromatic carbocyclylcarbamoyl”, “substituted or unsubstituted aromatic heterocyclylcarbamoyl”, and “substituted or unsubstituted non-aromatic heterocyclylcarbamoyl”,
“substituted or unsubstituted aromatic carbocyclylsulfamoyl”, “substituted or unsubstituted non-aromatic carbocyclylsulfamoyl”, “substituted or unsubstituted aromatic heterocyclylsulfamoyl”, and “substituted or unsubstituted non-aromatic heterocyclylsulfamoyl”,
“substituted or unsubstituted aromatic carbocyclylcarbonylamino”, “substituted or unsubstituted non-aromatic carbocyclylcarbonylamino”, “substituted or unsubstituted aromatic heterocyclylcarbonylamino”, and “substituted or unsubstituted non-aromatic heterocyclylcarbonylamino”,
“substituted or unsubstituted aromatic carbocyclylsulfonylamino”, “substituted or unsubstituted non-aromatic carbocyclylsulfonylamino”, “substituted or unsubstituted aromatic heterocyclylsulfonylamino”, and “substituted or unsubstituted non-aromatic heterocyclylsulfonylamino”, and
“substituted or unsubstituted aromatic carbocyclyloxycarbonylamino”, “substituted or unsubstituted non-aromatic carbocyclyloxycarbonylamino”, “substituted or unsubstituted aromatic heterocyclyloxycarbonylamino”, and “substituted or unsubstituted non-aromatic heterocyclyloxycarbonylamino” include the substituent group D. An atom at any position(s) on the ring may be bonded to one or more group(s) selected from the substituent group G.

(215) The substituent group C: halogen, hydroxy, carboxy, amino, carbamoyl, sulfamoyl, sulfo, cyano, alkyl optionally substituted with one or more group(s) selected from the substituent group D, alkenyl optionally substituted with one or more group(s) selected from the substituent group D, alkynyl optionally substituted with one or more group(s) selected from the substituent group D, alkyloxy optionally substituted with one or more group(s) selected from the substituent group D, alkenyloxy optionally substituted with one or more group(s) selected from the substituent, group D, alkynyloxy optionally substituted with one or more group(s) selected from the substituent group D, alkylamino optionally substituted with one or more group(s) selected from the substituent group D, alkenylamino optionally substituted with one or more group(s) selected from the substituent group D, alkynylamino optionally substituted with one or more group(s) selected from the substituent group U, alkylsulfanyl optionally substituted with one or more group(s) selected from the substituent group D, alkenylsulfanyl optionally substituted with one or more group(s) selected from the substituent group D, alkynylsulfanyl optionally substituted with one or more group(s) selected from the substituent group D, alkylcarbonyl optionally substituted with one or more group(s) selected from the substituent group D, alkylsulfonyl optionally substituted with one or more group(s) selected from the substituent group D, alkylcarbonylamino optionally substituted with one or more group(s) selected from the substituent group D, alkylsulfonylamino optionally substituted with one or more group(s) selected from the substituent group D, alkylcarbamoyl optionally substituted with one or more group(s) selected from the substituent group D, alkylsulfamoyl optionally substituted with one or more group(s) selected from the substituent group D, alkylcarbonyloxy optionally substituted with one or more group(s) selected from the substituent group D, alkyloxycarbonyl optionally substituted with one or more group(s) selected from the substituent group D, alkylsulfonyloxy optionally substituted with one or more group(s) selected from the substituent group D, aryloxysulfonyl optionally substituted with one or more group(s) selected from the substituent group D, aromatic carbocyclyl optionally substituted with one or more group(s) selected from the substituent group E, non-aromatic carbocyclyl optionally substituted with one or more group(s) selected from the substituent group E, aromatic heterocyclyl optionally substituted with one or more group (s) selected from the substituent group E, non-aromatic heterocyclyl optionally substituted with one or more group(s) selected from the substituent group E, aromatic, carbocyclyloxy optionally substituted with one or more group(s) selected from the substituent group E, non-aromatic carbocyclyloxy optionally substituted with one or more group(s) selected from the substituent group E, aromatic heterocyclyloxy optionally substituted with one or more group(s) selected from the substituent group E, non-aromatic heterocyclyloxy optionally substituted with one or more group(s) selected from the substituent group E, aromatic carbocyclylsulfanyl optionally substituted with one or more group(s) selected from the substituent group E, non-aromatic carbocyclylsulfanyl optionally substituted with one or more group(s) selected from the substituent group E, aromatic heterocyclylsulfanyl optionally substituted with one or more group(s) selected from the substituent group E, non-aromatic heterocyclylsulfanyl optionally substituted with one or more group(s) selected from the substituent group E, aromatic carbocyclyl amino optionally substituted with one or more group(s) selected from the substituent group E, non-aromatic carbocyclylamino optionally substituted with one or more group(s) selected from the substituent group E, aromatic heterocyclylamino optionally substituted with one or more group(s) selected from the substituent group E, non-aromatic heterocyclylamino optionally substituted with one or more group(s) selected from the substituent group E, aromatic carbocyclylcarbonyl optionally substituted with one or more group(s) selected from the substituent group E, non-aromatic carbocyclylcarbonyl optionally substituted with one or more group(s) selected from the substituent group E, aromatic heterocyclylcarbonyl optionally substituted with one or more group(s) selected from the substituent group E, non-aromatic heterocyclylcarbonyl optionally substituted with one or more group(s) selected from the substituent group E, aromatic carbocyclyl sulfonyl optionally substituted with one or more group(s) selected from the substituent group E, non-aromatic carbocyclylsulfonyl optionally substituted with one or more group(s) selected from the substituent group E, aromatic heterocyclylsulfonyl optionally substituted with one or more group(s) selected from the substituent group E, non-aromatic heterocyclylsulfonyl optionally substituted with one or more group(s) selected from the substituent group E, aromatic carbocyclylcarbonylamino optionally substituted with one or more group(s) selected from the substituent group E, non-aromatic carbocyclylcarbonylamino optionally substituted with one or more group(s) selected from the substituent group E, aromatic heterocyclylcarbonylamino optionally substituted with one or more group(s) selected from the substituent group E, non-aromatic heterocyclylcarbonylamino optionally substituted with one or more group(s) selected from the substituent group E, aromatic carbocyclylsulfonylamino optionally substituted with one or more group(s) selected from the substituent group E, non-aromatic carbocyclylsulfonylamino optionally substituted with one or more group(s) selected from the substituent group E, aromatic heterocyclylsulfonylamino optionally substituted with one or more group(s) selected from the substituent group E, non-aromatic heterocyclylsulfonylamino optionally substituted with one or more group(s) selected from the substituent group E, aromatic carbocyclylcarbamoyl optionally substituted with one or more group(s) selected from the substituent group E, non-aromatic carbocyclylcarbamoyl optionally substituted with one or more group(s) selected from the substituent group E, aromatic heterocyclylcarbamoyl optionally substituted with one or more group(s) selected from the substituent, group E, non-aromatic heterocyclylcarbamoyl optionally substituted with one or more group(s) selected from the substituent group E, aromatic carbocyclylsulfamoyl optionally substituted with one or more group(s) selected from the substituent group E, non-aromatic carbocyclylsulfamoyl optionally substituted with one or more group(s) selected from the substituent group E, aromatic heterocyclylsulfamoyl optionally substituted with one or more group(s) selected from the substituent, group E, non-aromatic heterocyclylsulfamoyl optionally substituted with one or more group(s) selected from the substituent group E, aromatic carbocyclyloxycarbonyl optionally substituted with one or more group(s) selected from the substituent group E, non-aromatic carbocyclyloxycarbonyl optionally substituted with one or more group(s) selected from the substituent group E, aromatic heterocyclyloxycarbonyl optionally substituted with one or more group(s) selected from the substituent group E, non-aromatic heterocyclyloxycarbonyl optionally substituted with one or more group(s) selected from the substituent group E, aromatic carbocyclyloxysulfonyl optionally substituted with one or more group(s) selected from the substituent group E, non-aromatic carbocyclyloxysulfonyl optionally substituted with one or more group(s) selected from the substituent group E, aromatic heterocyclyloxysulfonyl optionally substituted with one or more group(s) selected from the substituent group E, non-aromatic heterocyclyloxysulfonyl optionally substituted with one or more group(s) selected from the substituent group E, aromatic carbocyclylcarbonyloxy optionally substituted with one or more group(s) selected from the substituent group E, non-aromatic carbocyclylcarbonyloxy optionally substituted with one or more group(s) selected from the substituent group E, aromatic heterocyclylcarbonyloxy optionally substituted with one or more group(s) selected from the substituent group E, non-aromatic heterocyclylcarbonyloxy optionally substituted with one or more group(s) selected from the substituent group E, aromatic, carbocyclyl sulfonyloxy optionally substituted with one or more group(s) selected from the substituent group E, non-aromatic carbocyclyl sulfon yloxy optionally substituted with one or more group(s) selected from the substituent group E, aromatic heterocyclylsulfonyloxy optionally substituted with one or more group(s) selected from the substituent group E, and non-aromatic heterocyclylsulfonyloxy optionally substituted with one or more group(s) selected from the substituent group E.

(216) The substituent group C: halogen, hydroxy, carboxy, amino, carbamoyl, sulfamoyl, sulfo, cyano, alkyloxy, haloalkyloxy, alkylamino, haloalkylamino, alkylsulfanyl, haloalkylsulfanyl, and

(217) aromatic carbocyclyl optionally substituted with one or more group(s) selected from the substituent group F, non-aromatic carbocyclyl optionally substituted with one or more group(s) selected from the substituent group F, aromatic heterocyclyl optionally substituted with one or more group(s) selected from the substituent, group F, and non-aromatic heterocyclyl optionally substituted with one or more group(s) selected from the substituent group F.

(218) The substituent group D: halogen, hydroxy, carboxy, amino, carbamoyl, sulfamoyl, sulfo, and cyano.

(219) The substituent group E: halogen, hydroxy, carboxy, amino, carbamoyl, sulfamoyl, sulfo, and cyano, and

(220) alkyl optionally substituted with one or more group(s) selected from the substituent group D, alkyloxy optionally substituted with one or more group(s) selected from the substituent group D, alkylamino optionally substituted with one or more group (a) selected from the substituent group D, alkylsulfanyl optionally substituted with one or more group(s) selected from the substituent group D, alkylcarbonyl optionally substituted with one or more group(s) selected from the substituent, group D, alkylsulfonyl optionally substituted with one or more group(s) selected from the substituent group D, alkylcarbonylamino optionally substituted with one or more group(s) selected from the substituent group D, alkylsulfonylamino optionally substituted with one or more group(s) selected from the substituent group D, alkylcarbamoyl optionally substituted with one or more group(s) selected from the substituent group D, alkylsulfamoyl optionally substituted with one or more group(s) selected from the substituent group D, alkylcarbonyloxy optionally substituted with one or more group(s) selected from the substituent group D, alkyloxycarbonyl optionally substituted with one or more group(s) selected from the substituent group D, alkylsulfonyloxy optionally substituted with one or more group(s) selected from the substituent group D, and aryloxysulfonyl optionally substituted with one or more group(s) selected from the substituent group D.

(221) The substituent group F: halogen, hydroxy, carboxy, amino, carbamoyl, sulfamoyl, sulfo, cyano, alkyl, haloalkyl, alkyloxy, haloaryloxy, alkylamino, haloalkylamino, alkylsulfanyl, haloalkylsulfanyl, alkylcarbonyl, haloalkylcarbonyl, alkylsulfonyl, haloalkylsulfonyl, alkylcarbonylamino, haloalkylcarbonylamino, alkylsulfonylamino, haloalkylsulfonylamino, alkylcarbamoyl, haloalkylcarbamoyl, alkylsulfamoyl, and haloalkylsulfamoyl.

(222) “Substituted or unsubstituted non-aromatic carbocyclyl” and “substituted or unsubstituted non-aromatic heterocyclyl” may be optionally substituted with one or more group(s) selected from “oxo”. In this case, it means a group wherein two hydrogen atoms on a carbon atom are replaced as below.

(223) ##STR00039##

(224) The non-aromatic carbocycle or non-aromatic heterocycle part of the above “non-aromatic carbocyclyloxy”, “non-aromatic carbocyclylamino”, “non-aromatic carbocyclylsulfanyl”, “non-aromatic carbocyclylcarbonyl”, “non-aromatic carbocyclylsulfonyl”, “non-aromatic carbocyclylcarbonyloxy”, “non-aromatic carbocyclylsulfonyloxy”, “non-aromatic carbocyclyloxycarbonyl”, “non-aromatic carbocyclyloxysulfonyl”, “non-aromatic carbocyclylcarbamoyl”, “non-aromatic carbocyclylsulfamoyl”, “non-aromatic carbocyclylcarbonylamino”, “non-aromatic carbocyclylsulfonylamino”, “non-aromatic carbocyclyloxycarbonylamino”, “non-aromatic heterocyclyloxy”, “non-aromatic heterocyclylamino”, “non-aromatic heterocyclylsulfanyl”, “non-aromatic heterocyclyl carbonyl”, “non-aromatic heterocyclylsulfonyl”, “non-aromatic heterocyclylcarbonyloxy”, “non-aromatic heterocyclylsulfonyloxy”, “non-aromatic heterocyclyloxycarbonyl”, “non-aromatic heterocyclyloxysulfonyl”, “non aromatic heterocyclylcarbamoyl”, “non-aromatic heterocyclylsulfamoyl”, “non-aromatic heterocyclylcarbonylamino”, “non-aromatic heterocyclylsulfonylamino”, and “non-aromatic heterocyclyloxycarbonylamino” may be optionally substituted with one or more group(s) selected from “oxo” as above.

(225) The substituents on the rings of “substituted or unsubstituted aromatic carbocyclyl”, “substituted or unsubstituted non-aromatic carbocyclyl”, “substituted or unsubstituted aromatic heterocyclyl”, “substituted or unsubstituted non-aromatic heterocyclyl”, “substituted or unsubstituted 5- to 10-membered aromatic carbocyclyl”, “substituted or unsubstituted 3- to 10-membered non-aromatic carbocyclyl”, “substituted or unsubstituted 5- to 10-membered aromatic heterocyclyl”, “substituted or unsubstituted 3- to 10-membered non-aromatic heterocyclyl”, “substituted or unsubstituted 6-membered aromatic carbocyclyl”, “substituted or unsubstituted 3- to 6-membered non-aromatic carbocyclyl”, “substituted or unsubstituted 5- to 6-membered aromatic heterocyclyl”, and “substituted or unsubstituted 5- to 6-membered non-aromatic heterocyclyl” in R.sup.1 include, for example, halogen, hydroxy, carboxy, amino, carbamoyl, sulfamoyl, sulfo, cyano, alkyl optionally substituted with one or more group(s) selected from the substituent group D, alkyloxy optionally substituted with one or more group(s) selected from the substituent group D, alkylamino optionally substituted with one or more group(s) selected from the substituent group D, alkylsulfanyl optionally substituted with one or more group(s) selected from the substituent group D, alkylcarbonyl optionally substituted with one or more group(s) selected from the substituent group D, alkylsulfonyl optionally substituted with one or more group(s) selected from the substituent group D, alkylcarbonylamino optionally substituted with one or more group(s) selected from the substituent group D, alkylsulfonylamino optionally substituted with one or more group(s) selected from the substituent group D, alkylcarbamoyl optionally substituted with one or more group(s) selected from the substituent group D, alkylsulfamoyl optionally substituted with one or more group(s) selected from the substituent group D and the like.

(226) One embodiment, is, for example, halogen, hydroxy, carboxy, amino, carbamoyl, sulfamoyl, sulfo, cyano, alkyl, haloalkyl, alkyloxy, haloaryloxy, alkylamino, haloalkylamino, alkylsulfanyl, haloalkylsulfanyl, alkylcarbonyl, haloalkylcarbonyl, alkylsulfonyl, haloalkylsulfonyl, alkylcarbonylamino, haloalkylcarbonylamino, alkylsulfonylamino, haloalkylsulfonylamino, alkylcarbamoyl, haloalkylcarbamoyl, alkylsulfamoyl, haloalkylsulfamoyl, or the like.

(227) One embodiment is, for example, halogen, hydroxy, cyano, alkyl optionally substituted with one or more group(s) selected from the substituent, group D, alkyloxy optionally substituted with one or more group(s) selected from the substituent group D, alkylamino optionally substituted with one or more group(s) selected from the substituent group D, alkylsulfanyl optionally substituted with one or more group Os) selected from the substituent group D or the like.

(228) One embodiment is, for example, halogen, alkyl, haloalkyl, alkyloxy, haloaryloxy, alkylamino, haloalkylamino, alkylsulfanyl, haloalkylsulfanyl or the like.

(229) One embodiment is, for example, halogen, alkyl optionally substituted with one or more group(s) selected from the substituent group D, alkyloxy optionally substituted with one or more group(s) selected from the substituent group D or the like.

(230) One embodiment is, for example, halogen, alkyl, haloalkyl, alkyloxy, haloalkyloxy or the like.

(231) One embodiment is, for example, halogen, alkyl, haloalkyl or the like.

(232) One embodiment is, for example, halogen.

(233) One embodiment is, for example, halogen, cyano, alkyl optionally substituted with one or more group(s) selected from the substituent group D, alkyloxy optionally substituted with one or more group(s) selected from the substituent group D or the like.

(234) One embodiment is, for example, halogen, cyano, alkyl, haloalkyl, alkyloxy, haloalkyloxy or the like.

(235) The substituents of “substituted or unsubstituted alkyl”, and “substituted or unsubstituted alkyloxy” in R.sup.2a, R.sup.2b, R.sup.2c, R.sup.2d, R.sup.8a and R.sup.8b include, for example, halogen, hydroxy, carboxy, amino, carbamoyl, sulfamoyl, sulfo, cyano, alkyloxy optionally substituted with one or more group(s) selected from the substituent group D, alkylamino optionally substituted with one or more group(s) selected from the substituent group D, alkylsulfanyl optionally substituted with one or more group(s) selected from the substituent group D, alkylcarbonyl optionally substituted with one or more group(s) selected from the substituent group D, alkylsulfonyl optionally substituted with one or more group(s) selected from the substituent group D, alkylcarbonylamino optionally substituted with one or more group(s) selected from the substituent group D, alkylsulfonylamino optionally substituted with one or more group(s) selected from the substituent group D, aromatic carbocyclyl optionally substituted with one or more group(s) selected from the substituent group F, non-aromatic carbocyclyl optionally substituted with one or more group(s) selected from the substituent group F, aromatic heterocyclyl optionally substituted with one or more group(s) selected from the substituent group F, non-aromatic heterocyclyl optionally substituted with one or more group(s) selected from the substituent group F and the like.

(236) One embodiment is, for example, halogen, hydroxy, carboxy, amino, carbamoyl, sulfamoyl, sulfo, cyano or the like.

(237) One embodiment is, for example, halogen, hydroxy, cyano or the like.

(238) One embodiment is, for example, halogen or the like.

(239) The substituents of “substituted or unsubstituted alkyl”, and “substituted or unsubstituted alkylcarbonyl” in R.sup.7a include, for example, halogen, hydroxy, carboxy, amino, carbamoyl, sulfamoyl, sulfo, cyano, alkyloxy optionally substituted with one or more group(s) selected from the substituent group D, alkylamino optionally substituted with one or more group(s) selected from the substituent group D, alkylsulfanyl optionally substituted with one or more group(s) selected from the substituent, group D, alkylcarbonyl optionally substituted with one or more group(s) selected from the substituent group D, alkylsulfonyl optionally substituted with one or more group(s) selected from the substituent group D, alkylcarbonylamino optionally substituted with one or more group(s) selected from the substituent group D, alkylsulfonylamino optionally substituted with one or more group(s) selected from the substituent group D, aromatic carbocyclyl optionally substituted with one or more group(s) selected from the substituent, group F, non-aromatic carbocyclyl optionally substituted with one or more group(s) selected from the substituent group F, aromatic heterocyclyl optionally substituted with one or more group(s) selected from the substituent, group F, non-aromatic heterocyclyl optionally substituted with one or more group(s) selected from the substituent group F and the like.

(240) One embodiment is, for example, halogen, hydroxy, carboxy, amino, carbamoyl, sulfamoyl, sulfo, cyano or the like.

(241) One embodiment is, for example, halogen, hydroxy, cyano or the like.

(242) One embodiment is, for example, halogen or the like.

(243) The substituents of “substituted or unsubstituted alkyl”, “substituted or unsubstituted alkenyl”, “substituted or unsubstituted alkynyl”, “substituted or unsubstituted alkyloxy”, “substituted or unsubstituted alkenyloxy”, “substituted or unsubstituted alkynyloxy”, “substituted or unsubstituted alkylsulfanyl”, “substituted or unsubstituted alkenylsulfanyl”, “substituted or unsubstituted alkynylsulfanyl”. “substituted or unsubstituted alkylamino”, “substituted or unsubstituted alkenylamino”, and “substituted or unsubstituted alkynylamino” in R.sup.4 and R.sup.6 include, for example, halogen, hydroxy, carboxy, amino, carbamoyl, sulfamoyl, sulfo, cyano, alkyloxy optionally substituted with one or more group(s) selected from the substituent group D, alkylamino optionally substituted with one or more group(s) selected from the substituent group D, alkylsulfanyl optionally substituted with one or more group(s) selected from the substituent group D, alkylcarbonyl optionally substituted with one or more group(s) selected from the substituent group D, alkylsulfonyl optionally substituted with one or more group(s) selected from the substituent group D, alkylcarbonylamino optionally substituted with one or more group(s) selected from the substituent group D, alkylsulfonylamino optionally substituted with one or more group(s) selected from the substituent group D, aromatic carbocyclyl optionally substituted with one or more group(s) selected from the substituent group F, non-aromatic carbocyclyl optionally substituted with one or more group(s) selected from the substituent group F, aromatic heterocyclyl optionally substituted with one or more group(s) selected from the substituent, group F, non-aromatic heterocyclyl optionally substituted with one or more group(s) selected from the substituent group F and the like.

(244) One embodiment is, for example, halogen, hydroxy, carboxy, amino, carbamoyl, sulfamoyl, sulfo, cyano or the like.

(245) One embodiment is, for example, halogen, hydroxy, cyano or the like.

(246) One embodiment is, for example, halogen.

(247) The substituents of “substituted or unsubstituted alkyl” in R.sup.5a, R.sup.5a′ and R.sup.5b include halogen, hydroxy, carboxy, amino, carbamoyl, sulfamoyl, sulfo, cyano, alkyloxy optionally substituted with one or more group(s) selected from the substituent group C, alkylamino optionally substituted with one or more group(s) selected from the substituent group C, alkylsulfanyl optionally substituted with one or more group(s) selected from the substituent group C, alkylcarbonyl optionally substituted with one or more group(s) selected from the substituent group C, alkylsulfonyl optionally substituted with one or more group(s) selected from the substituent group C, alkylcarbonylamino optionally substituted with one or more group(s) selected from the substituent group C, alkylsulfonylamino optionally substituted with one or more group(s) selected from the substituent group C, alkylcarbamoyl optionally substituted with one or more group(s) selected from the substituent group C, alkylsulfamoyl optionally substituted with one or more group(s) selected from the substituent group C, aromatic carbocyclyl optionally substituted with one or more group(s) selected from the substituent group E, non-aromatic carbocyclyl optionally substituted with one or more group(s) selected from the substituent group E, aromatic heterocyclyl optionally substituted with one or more group(s) selected from the substituent group E, non aromatic heterocyclyl optionally substituted with one or more group(s) selected from the substituent, group E, aromatic carbocyclyloxy optionally substituted with one or more group(s) selected from the substituent group E, non-aromatic carbocyclyloxy optionally substituted with one or more group(s) selected from the substituent group E, aromatic heterocyclyloxy optionally substituted with one or more group(s) selected from the substituent group E, non-aromatic heterocyclyloxy optionally substituted with one or more group(s) selected from the substituent group E, aromatic carbocyclylsulfanyl optionally substituted with one or more group(s) selected from the substituent, group E, non-aromatic carbocyclylsulfanyl optionally substituted with one or more group(s) selected from the substituent group E, aromatic heterocyclylsulfanyl optionally substituted with one or more group(s) selected from the substituent group E, non-aromatic heterocyclylsulfanyl optionally substituted with one or more group(s) selected from the substituent group E, aromatic carbocyclyl amino optionally substituted with one or more group(s) selected from the substituent group E, non-aromatic carbocyclylamino optionally substituted with one or more group(s) selected from the substituent group E, aromatic heterocyclylamino optionally substituted with one or more group(s) selected from the substituent, group E, non-aromatic heterocyclylamino optionally substituted with one or more group(s) selected from the substituent group E, aromatic carbocyclylcarbonyl optionally substituted with one or more group(s) selected from the substituent group E, non-aromatic carbocyclylcarbonyl optionally substituted with one or more group(s) selected from the substituent group E, aromatic heterocyclylcarbonyl optionally substituted with one or more group(s) selected from the substituent group E, non-aromatic heterocyclylcarbonyl optionally substituted with one or more group(s) selected from the substituent group E, aromatic carbocyclyl sulfonyl optionally substituted with one or more group(s) selected from the substituent group E, non-aromatic carbocyclylsulfonyl optionally substituted with one or more group(s) selected from the substituent group E, aromatic heterocyclylsulfonyl optionally substituted with one or more group(s) selected from the substituent group E, non-aromatic heterocyclylsulfonyl optionally substituted with one or more group(s) selected from the substituent group E, aromatic carbocyclylcarbonylamino optionally substituted with one or more group(s) selected from the substituent group E, non-aromatic carbocyclylcarbonylamino optionally substituted with one or more group(s) selected from the substituent group E, aromatic heterocyclylcarbonylamino optionally substituted with one or more group(s) selected from the substituent group E, non-aromatic heterocyclylcarbonylamino optionally substituted with one or more group(s) selected from the substituent group E, aromatic carbocyclylsulfonylamino optionally substituted with one or more group(s) selected from the substituent group E, non-aromatic carbocyclylsulfonylamino optionally substituted with one or more group(s) selected from the substituent group E, aromatic heterocyclylsulfonylamino optionally substituted with one or more group(s) selected from the substituent group E, non-aromatic heterocyclylsulfonylamino optionally substituted with one or more group(s) selected from the substituent group E, aromatic carbocyclylcarbamoyl optionally substituted with one or more group(s) selected from the substituent group E, non-aromatic carbocyclylcarbamoyl optionally substituted with one or more group(s) selected from the substituent group E, aromatic heterocyclylcarbamoyl optionally substituted with one or more group(s) selected from the substituent, group E, non-aromatic heterocyclylcarbamoyl optionally substituted with one or more group(s) selected from the substituent group E, aromatic carbocyclylsulfamoyl optionally substituted with one or more group(s) selected from the substituent group E, non-aromatic carbocyclylsulfamoyl optionally substituted with one or more group(s) selected from the substituent group E, aromatic heterocyclylsulfamoyl optionally substituted with one or more group(s) selected from the substituent, group E, non-aromatic heterocyclylsulfamoyl optionally substituted with one or more group(s) selected from the substituent group E and the like.

(248) One embodiment is, for example, halogen, hydroxy, carboxy, amino, carbamoyl, sulfamoyl, sulfo, cyano, alkylcarbonyl optionally substituted with one or more group(s) selected from the substituent group C, alkylcarbonylamino optionally substituted with one or more group(s) selected from the substituent group C, alkylcarbamoyl optionally substituted with one or more group(s) selected from the substituent group C, aromatic carbocyclylcarbonyl optionally substituted with one or more group(s) selected from the substituent group F, non-aromatic carbocyclylcarbonyl optionally substituted with one or more group(s) selected from the substituent group F, aromatic heterocyclylcarbonyl optionally substituted with one or more group(s) selected from the substituent group F, non-aromatic heterocyclylcarbonyl optionally substituted with one or more group(s) selected from the substituent, group F, aromatic carbocyclylcarbonylamino optionally substituted with one or more group(s) selected from the substituent group F, non-aromatic carbocyclylcarbonylamino optionally substituted with one or more group(s) selected from the substituent group F, aromatic heterocyclylcarbonyl amino optionally substituted with one or more group(s) selected from the substituent group F, non-aromatic heterocyclylcarbonyl amino optionally substituted with one or more group(s) selected from the substituent group F, aromatic carbocyclylcarbamoyl optionally substituted with one or more group(s) selected from the substituent group F, non-aromatic carbocyclylcarbamoyl optionally substituted with one or more group(s) selected from the substituent group F, aromatic heterocyclylcarbamoyl optionally substituted with one or more group(s) selected from the substituent group F, non-aromatic heterocyclylcarbamoyl optionally substituted with one or more group(s) selected from the substituent group F or the like.

(249) One embodiment is, for example, halogen, hydroxy, carboxy, carbamoyl, cyano, alkylcarbamoyl optionally substituted with one or more group(s) selected from the substituent group C, aromatic carbocyclylcarbonyl optionally substituted with one or more group(s) selected from the substituent group F, non-aromatic carbocyclylcarbonyl optionally substituted with one or more group(s) selected from the substituent group F, aromatic heterocyclylcarbonyl optionally substituted with one or more group(s) selected from the substituent group F, non-aromatic heterocyclylcarbonyl optionally substituted with one or more group(s) selected from the substituent, group F, aromatic carbocyclylcarbamoyl optionally substituted with one or more group(s) selected from the substituent group F, non-aromatic carbocyclylcarbamoyl optionally substituted with one or mom group(s) selected from the substituent group F, aromatic heterocyclylcarbamoyl optionally substituted with one or more group(s) selected from the substituent-group F, non-aromatic heterocyclylcarbamoyl optionally substituted with one or more group(s) selected from the substituent group F or the like.

(250) One embodiment is, for example, halogen, hydroxy, carboxy, carbamoyl, alkylcarbamoyl optionally substituted with one or mom group(s) selected from (hydroxy, cyano and alkyloxy), non-aromatic heterocyclylcarbonyl, aromatic carbocyclylcarbamoyl optionally substituted with one or more group(s) selected from (halogen and alkyl), non-aromatic heterocyclylcarbamoyl, or the like.

(251) The substituents of “substituted or unsubstituted alkylcarbamoyl” in R.sup.6a, R.sup.5a′ and R.sup.5b include halogen, hydroxy, carboxy, amino, carbamoyl, sulfamoyl, sulfo, cyano, alkyloxy optionally substituted with one or more group(s) selected from the substituent group D, alkylamino optionally substituted with one or more group(s) selected from the substituent group D, alkylsulfanyl optionally substituted with one or more group(s) selected from the substituent group D, alkylcarbonyl optionally substituted with one or more group(s) selected from the substituent group D, alkylsulfonyl optionally substituted with one or mom group(s) selected from the substituent, group D, alkylcarbonylamino optionally substituted with one or more group(s) selected from the substituent group D, alkylsulfonylamino optionally substituted with one or more group(s) selected from the substituent group D, alkylcarbamoyl optionally substituted with one or more group(s) selected from the substituent group D, alkylsulfamoyl optionally substituted with one or more group(s) selected from the substituent group D, aromatic carbocyclyl optionally substituted with one or more group(s) selected from the substituent group F, non-aromatic carbocyclyl optionally substituted with one or more group(s) selected from the substituent group F, aromatic heterocyclyl optionally substituted with one or more group(s) selected from the substituent group F, non-aromatic heterocyclyl optionally substituted with one or more group(s) selected from the substituent group F, aromatic carbocyclyloxy optionally substituted with one or more group(s) selected from the substituent group F, non-aromatic carbocyclyloxy optionally substituted with one or more group(s) selected from the substituent group F, aromatic heterocyclyloxy optionally substituted with one or more group(s) selected from the substituent group F, non-aromatic heterocyclyloxy optionally substituted with one or more group(s) selected from the substituent group F, aromatic carbocyclylsulfanyl optionally substituted with one or more group(s) selected from the substituent group F, non-aromatic carbocyclylsulfanyl optionally substituted with one or more group(s) selected from the substituent group F, aromatic heterocyclylsulfanyl optionally substituted with one or more group(s) selected from the substituent group F, non-aromatic heterocyclylsulfanyl optionally substituted with one or more group(s) selected from the substituent group F, aromatic carbocyclylamino optionally substituted with one or more group(s) selected from the substituent group F, non-aromatic carbocyclylamino optionally substituted with one or more group(s) selected from the substituent group F, aromatic heterocyclylamino optionally substituted with one or more group(s) selected from the substituent group F, non-aromatic heterocyclylamino optionally substituted with one or more group(s) selected from the substituent group F and the like.

(252) One embodiment is, for example, halogen, hydroxy, carboxy, amino, carbamoyl, sulfamoyl, sulfo, cyano, alkyloxy optionally substituted with one or more group(s) selected from the substituent group D, alkylamino optionally substituted with one or more group(s) selected from the substituent group D, alkylsulfanyl optionally substituted with one or more group(s) selected from the substituent group D, alkylcarbonyl optionally substituted with one or more group(s) selected from the substituent, group D, alkylsulfonyl optionally substituted with one or more group(s) selected from the substituent group D, alkylcarbonylamino optionally substituted with one or more group(s) selected from the substituent group D, alkylsulfonylamino optionally substituted with one or more group(s) selected from the substituent group D, alkylcarbamoyl optionally substituted with one or more group(s) selected from the substituent group D, alkylsulfamoyl optionally substituted with one or more group(s) selected from the substituent group D, aromatic carbocyclyl optionally substituted with one or more group(s) selected from the substituent group F, non-aromatic carbocyclyl optionally substituted with one or more group (s) selected from the substituent group F, aromatic heterocyclyl optionally substituted with one or more group(s) selected from the substituent group F, non-aromatic heterocyclyl optionally substituted with one or more group(s) selected from the substituent group F or the like.

(253) One embodiment, is, for example, halogen, hydroxy, cyano, alkyloxy optionally substituted with one or more group(s) selected from the substituent group D, alkylcarbonyl optionally substituted with one or more group(s) selected from the substituent, group D, alkylsulfonyl optionally substituted with one or more group(s) selected from the substituent group D, alkylcarbamoyl optionally substituted with one or more group(s) selected from the substituent group D, aromatic carbocyclyl optionally substituted with one or more group(s) selected from the substituent group F, non-aromatic carbocyclyl optionally substituted with one or more group(s) selected from the substituent group F, aromatic heterocyclyl optionally substituted with one or more group(s) selected from the substituent group F, non-aromatic heterocyclyl optionally substituted with one or more group(s) selected from the substituent group F or the like.

(254) One embodiment is, for example, halogen, cyano, alkyloxy, alkylcarbonyl, alkylsulfonyl, alkylcarbamoyl, aromatic carbocyclyl or the like.

(255) The substituents of “substituted or unsubstituted alkenyl”, “substituted or unsubstituted alkynyl”, “substituted or unsubstituted alkyloxy”, “substituted or unsubstituted alkenyloxy”, “substituted or unsubstituted alkynyloxy”, “substituted or unsubstituted alkylsulfanyl”, “substituted or unsubstituted alkenylsulfanyl”, “substituted or unsubstituted alkynyl sulfanyl”, “substituted or unsubstituted alkylamino”, “substituted or unsubstituted alkenylamino”, “substituted or unsubstituted alkynylamino”, “substituted or unsubstituted alkylcarbonyl”, “substituted or unsubstituted alkenylcarbonyl”, “substituted or unsubstituted alkynylcarbonyl”, “substituted or unsubstituted alkylsulfonyl”, “substituted or unsubstituted alkenylsulfonyl”, “substituted or unsubstituted alkynylsulfinyl”, “substituted or unsubstituted alkylcarbonyloxy”, “substituted or unsubstituted alkenylcarbonyloxy”, “substituted or unsubstituted alkynylcarbonyloxy”, “substituted or unsubstituted alkyloxycarbonyl”, “substituted or unsubstituted alkenyloxycarbonyl”, “substituted or unsubstituted alkynyloxycarbonyl”, “substituted or unsubstituted alkylsulfonyloxy”, “substituted or unsubstituted alkenylsulfonyloxy”, “substituted or unsubstituted alkynylsulfonyloxy”, “substituted or unsubstituted alkyloxysulfonyl”, “substituted or unsubstituted alkenyloxysulfonyl”, “substituted or unsubstituted alkynyloxysulfonyl”, “substituted or unsubstituted alkylcarbamoyl”, “substituted or unsubstituted alkenylcarbamoyl”, “substituted or unsubstituted alkynylcarbamoyl”, “substituted or unsubstituted alkylsulfamoyl”, “substituted or unsubstituted alkenylsulfamoyl”, “substituted or unsubstituted alkynylsulfamoyl”, “substituted or unsubstituted alkylcarbonylamino”, “substituted or unsubstituted alkenylcarbonylamino”, “substituted or unsubstituted alkynylcarbonylamino”, “substituted or unsubstituted alkylsulfonylamino”, “substituted or unsubstituted alkenylsulfonylamino”, “substituted or unsubstituted alkyloxycarbonylamino”, “substituted or unsubstituted alkenyloxycarbonyl amino”, and “substituted or unsubstituted alkynyloxycarbonylamino” in R.sup.5a, ligand R.sup.5b include halogen, hydroxy, carboxy, amino, carbamoyl, sulfamoyl, sulfo, cyano, alkyloxy optionally substituted with one or more group(s) selected from the substituent group D, alkylamino optionally substituted with one or more group(s) selected from the substituent group D, alkylsulfanyl optionally substituted with one or more group(s) selected from the substituent group D, alkylcarbonyl optionally substituted with one or more group(s) selected from the substituent group D, alkylsulfonyl optionally substituted with one or more group(s) selected from the substituent, group D, alkylcarbonylamino optionally substituted with one or more group(s) selected from the substituent group D, alkylsulfonylamino optionally substituted with one or more group(s) selected from the substituent group D, alkylcarbamoyl optionally substituted with one or more group(s) selected from the substituent group D, alkylsulfamoyl optionally substituted with one or more group(s) selected from the substituent group D, aromatic carbocyclyl optionally substituted with one or more group(s) selected from the substituent group F, non-aromatic carbocyclyl optionally substituted with one or more group(s) selected from the substituent group F, aromatic heterocyclyl optionally substituted with one or more group(s) selected from the substituent group F, non-aromatic heterocyclyl optionally substituted with one or more group(s) selected from the substituent group F, aromatic carbocyclyloxy optionally substituted with one or more group(s) selected from the substituent group F, non-aromatic carbocyclyloxy optionally substituted with one or more group (a) selected from the substituent group F, aromatic heterocyclyloxy optionally substituted with one or more group(s) selected from the substituent group F, non-aromatic heterocyclyloxy optionally substituted with one or more group(s) selected from the substituent group F, aromatic carbocyclylsulfanyl optionally substituted with one or more group(s) selected from the substituent group F, non-aromatic carbocyclylsulfanyl optionally substituted with one or more group (s) selected from the substituent group F, aromatic heterocyclylsulfanyl optionally substituted with one or more group(s) selected from the substituent group F, non-aromatic heterocyclylsulfanyl optionally substituted with one or more group(s) selected from the substituent group F, aromatic carbocyclyl amino optionally substituted with one or more group(s) selected from the substituent group F, non-aromatic carbocyclylamino optionally substituted with one or more group(s) selected from the substituent group F, aromatic heterocyclylamino optionally substituted with one or more group(s) selected from the substituent group F, and non-aromatic heterocyclylamino optionally substituted with one or more group(s) selected from the substituent group F and the like.

(256) One embodiment is, for example, halogen, hydroxy, carboxy, amino, carbamoyl, sulfamoyl, sulfo, cyano, alkyloxy optionally substituted with one or more group (s) selected from the substituent group D, alkylamino optionally substituted with one or more group(s) selected from the substituent, group D, alkylsulfanyl optionally substituted with one or more group(s) selected from the substituent, group D, alkylcarbonyl optionally substituted with one or more group(s) selected from the substituent group D, alkylsulfonyl optionally substituted with one or more group(s) selected from the substituent group D, alkylcarbonylamino optionally substituted with one or more group(s) selected from the substituent group D, alkylsulfonylamino optionally substituted with one or more group(s) selected from the substituent group D, aromatic carbocyclyl optionally substituted with one or more group(s) selected from the substituent group F, non-aromatic carbocyclyl optionally substituted with one or more group(s) selected from the substituent group F, aromatic heterocyclyl optionally substituted with one or more group(s) selected from the substituent group F, non-aromatic heterocyclyl optionally substituted with one or more group(s) selected from the substituent group F or the like.

(257) One embodiment is, for example, halogen, hydroxy, cyano, aromatic carbocyclyl optionally substituted with one or more group(s) selected from the substituent group F, non-aromatic carbocyclyl optionally substituted with one or more group(s) selected from the substituent group F, aromatic heterocyclyl optionally substituted with one or more group(s) selected from the substituent group F, non-aromatic heterocyclyl optionally substituted with one or more group(s) selected from the substituent group F or the like.

(258) One embodiment is, for example, halogen, aromatic carbocyclyl or the like.

(259) One embodiment is, for example, halogen or the like.

(260) The substituents of “substituted or unsubstituted alkyl”, “substituted or unsubstituted alkenyl”, “substituted or unsubstituted alkynyl”, “substituted or unsubstituted alkyloxy”, “substituted or unsubstituted alkenyloxy”, “substituted or unsubstituted alkynyloxy”, “substituted or unsubstituted alkylsulfanyl”, “substituted or unsubstituted alkenylsulfonyl”, “substituted or unsubstituted alkynyl sulfanyl”, “substituted or unsubstituted alkylamino”, “substituted or unsubstituted alkenylamino”, “substituted or unsubstituted alkynylamino”, “substituted or unsubstituted alkylcarbonyl”, “substituted or unsubstituted alkenylcarbonyl”, “substituted or unsubstituted alkynylcarbonyl”, “substituted or unsubstituted alkylsulfonyl”, “substituted or unsubstituted alkenylsulfonyl”, “substituted or unsubstituted alkynylsulfonyl”, “substituted or unsubstituted alkylcarbonyloxy”, “substituted or unsubstituted alkenylcarbonyloxy”, “substituted or unsubstituted alkynylcarbonyloxy”, “substituted or unsubstituted alkyloxycarbonyl”, “substituted or unsubstituted alkenyloxycarbonyl”, “substituted or unsubstituted alkynyloxycarbonyl”, “substituted or unsubstituted alkylsulfonyloxy”, “substituted or unsubstituted alkenylsulfonyloxy”, “substituted or unsubstituted alkynylsulfonyloxy”, “substituted or unsubstituted aryloxysulfonyl”, “substituted or unsubstituted alkenyloxysulfonyl”, “substituted or unsubstituted alkynyloxysulfonyl”, “substituted or unsubstituted alkylcarbamoyl”, “substituted or unsubstituted alkenylcarbamoyl”, “substituted or unsubstituted alkynylcarbamoyl”, “substituted or unsubstituted alkylsulfamoyl”, “substituted or unsubstituted alkenylsulfamoyl”, “substituted or unsubstituted alkynylsulfamoyl”, “substituted or unsubstituted alkylcarbonylamino”, “substituted or unsubstituted alkenylcarbonylamino”, “substituted or unsubstituted alkynylcarbonylamino”, “substituted or unsubstituted alkylsulfonylamino”, “substituted or unsubstituted alkenylsulfonylamino”, “substituted or unsubstituted alkyloxycarbonylamino”, “substituted or unsubstituted alkenyloxycarbonylamino”, and “substituted or unsubstituted alkynyloxycarbonylamino” in R.sup.9a and R.sup.9b include, for example, halogen, hydroxy, carboxy, amino, carbamoyl, sulfamoyl, sulfo, cyano, alkyloxy optionally substituted with one or more group(s) selected from the substituent group D, alkylamino optionally substituted with one or more group (a) selected from the substituent group D, alkylsulfanyl optionally substituted with one or more group(s) selected from the substituent group D, alkylcarbonyl optionally substituted with one or more group(s) selected from the substituent group D, alkylsulfonyl optionally substituted with one or more group(s) selected from the substituent group D, alkylcarbonylamino optionally substituted with one or more group(s) selected from the substituent group D, alkylsulfonylamino optionally substituted with one or more group(s) selected from the substituent group D, alkylcarbamoyl optionally substituted with one or more group(s) selected from the substituent group D, alkylsulfamoyl optionally substituted with one or more group(s) selected from the substituent group D, aromatic carbocyclyl optionally substituted with one or more group(s) selected from the substituent group F, non-aromatic carbocyclyl optionally substituted with one or more group(s) selected from the substituent group F, aromatic heterocyclyl optionally substituted with one or more group(s) selected from the substituent group F, non-aromatic heterocyclyl optionally substituted with one or more group(s) selected from the substituent group F, aromatic carbocyclyloxy optionally substituted with one or more group(s) selected from the substituent group F, non-aromatic carbocyclyloxy optionally substituted with one or more group(s) selected from the substituent group F, aromatic heterocyclyloxy optionally substituted with one or more group(s) selected from the substituent group F, non-aromatic heterocyclyloxy optionally substituted with one or more group(s) selected from the substituent group F, aromatic carbocyclyl sulfanyl optionally substituted with one or more group(s) selected from the substituent group F, non-aromatic carbocyclylsulfanyl optionally substituted with one or more group(s) selected from the substituent group F, aromatic heterocyclylsulfanyl optionally substituted with one or more group(s) selected from the substituent group F, non-aromatic heterocyclylsulfanyl optionally substituted with one or more group(s) selected from the substituent group F, aromatic carbocyclylamino optionally substituted with one or more group(s) selected from the substituent, group F, non-aromatic carbocyclylamino optionally substituted with one or more group(s) selected from the substituent group F, aromatic heterocyclylamino optionally substituted with one or more group(s) selected from the substituent group F, and non-aromatic heterocyclylamino optionally substituted with one or more group(s) selected from the substituent group F and the like.

(261) One embodiment is, for example, halogen, hydroxy, carboxy, amino, carbamoyl, sulfamoyl, sulfo, cyano, alkyloxy optionally substituted with one or more group(s) selected from the substituent group D, alkylamino optionally substituted with one or more group (a) selected from the substituent group D, alkylsulfanyl optionally substituted with one or more group(s) selected from the substituent group D, aromatic carbocyclyl optionally substituted with one or more group(s) selected from the substituent group F, non-aromatic carbocyclyl optionally substituted with one or more group(s) selected from the substituent group F, aromatic heterocyclyl optionally substituted with one or more group(s) selected from the substituent group F, non-aromatic heterocyclyl optionally substituted with one or more group(s) selected from the substituent group F or the like.

(262) One embodiment is, for example, halogen, alkyloxy optionally substituted with one or more group(s) selected from the substituent group D, aromatic carbocyclyl optionally substituted with one or more group(s) selected from the substituent group F, nonaromatic carbocyclyl optionally substituted with one or more group(s) selected from the substituent group F, aromatic heterocyclyl optionally substituted with one or more group(s) selected from the substituent group F, non-aromatic heterocyclyl optionally substituted with one or more group(s) selected from the substituent group F or the like.

(263) One embodiment is, for example, halogen, aromatic carbocyclyl optionally substituted with one or more group(s) selected from the substituent group F, non-aromatic carbocyclyl optionally substituted with one or more group(s) selected from the substituent, group F, aromatic heterocyclyl optionally substituted with one or more group(s) selected from the substituent group F, non-aromatic heterocyclyl optionally substituted with one or more group(s) selected from the substituent group F or the like.

(264) One embodiment is, for example, halogen, aromatic carbocyclyl, aromatic heterocyclyl or the like.

(265) One embodiment is, for example, halogen or the like.

(266) The substituents on the rings of “aromatic carbocycle”, “non-aromatic carbocycle”, “aromatic heterocycle”, and “non-aromatic heterocycle” of

(267) “substituted or unsubstituted aromatic carbocyclyl”, “substituted or unsubstituted non-aromatic carbocyclyl”, “substituted or unsubstituted aromatic heterocyclyl”, and “substituted or unsubstituted non-aromatic heterocyclyl”.

(268) “substituted or unsubstituted aromatic carbocyclyloxy”, “substituted or unsubstituted non-aromatic carbocyclyloxy”, “substituted or unsubstituted aromatic heterocyclyloxy”, and “substituted or unsubstituted non-aromatic heterocyclyloxy”, “substituted or unsubstituted aromatic carbocyclylamino”, “substituted or unsubstituted non-aromatic carbocyclylamino”, “substituted or unsubstituted aromatic heterocyclylamino”, and “substituted or unsubstituted non-aromatic heterocyclylamino”,
“substituted or unsubstituted aromatic carbocyclylsulfanyl”, “substituted or unsubstituted non-aromatic carbocyclylsulfanyl”, “substituted or unsubstituted aromatic heterocyclyl sulfanyl”, and “substituted or unsubstituted non-aromatic heterocyclylsulfanyl”,
“substituted or unsubstituted aromatic carbocyclylcarbonyl”, “substituted or unsubstituted non-aromatic carbocyclylcarbonyl”, “substituted or unsubstituted aromatic heterocyclylcarbonyl”, and “substituted or unsubstituted non-aromatic heterocyclylcarbonyl”,
“substituted or unsubstituted aromatic carbocyclylsulfonyl”, “substituted or unsubstituted non-aromatic carbocyclylsulfonyl”, “substituted or unsubstituted aromatic heterocyclylsulfanyl”, and “substituted or unsubstituted non-aromatic heterocyclylsulfonyl”,
“substituted or unsubstituted aromatic carbocyclylcarbonyloxy”, “substituted or unsubstituted non-aromatic carbocyclylcarbonyloxy”, “substituted or unsubstituted aromatic heterocyclylcarbonyloxy”, and “substituted or unsubstituted non-aromatic heterocyclylcarbonyloxy”,
“substituted or unsubstituted aromatic carbocyclyloxycarbonyl”, “substituted or unsubstituted non-aromatic carbocyclyloxycarbonyl”, “substituted or unsubstituted aromatic heterocyclyloxycarbonyl”, and “substituted or unsubstituted non-aromatic heterocyclyloxycarbonyl”,
“substituted or unsubstituted aromatic carbocyclylsulfonyloxy”, “substituted or unsubstituted non-aromatic carbocyclylsulfonyloxy”, “substituted or unsubstituted aromatic heterocyclylsulfonyloxy”, and “substituted or unsubstituted non aromatic heterocyclylsulfonyloxy”,
“substituted or unsubstituted aromatic carbocyclyloxysulfonyl”, “substituted or unsubstituted non-aromatic carbocyclyloxysulfonyl”, “substituted or unsubstituted aromatic heterocyclyloxysulfonyl”, and “substituted or unsubstituted non-aromatic heterocyclyloxysulfonyl”,
“substituted or unsubstituted aromatic carbocyclylcarbamoyl”, “substituted or unsubstituted non-aromatic carbocyclylcarbamoyl”, “substituted or unsubstituted aromatic heterocyclylcarbamoyl”, and “substituted or unsubstituted non-aromatic heterocyclylcarbamoyl”,
“substituted or unsubstituted aromatic carbocyclylsulfamoyl”, “substituted or unsubstituted non-aromatic carbocyclylsulfamoyl”, “substituted or unsubstituted aromatic heterocyclylsulfamoyl”, and “substituted or unsubstituted non-aromatic heterocyclylsulfamoyl”,
“substituted or unsubstituted aromatic carbocyclylcarbonylamino”, “substituted or unsubstituted non-aromatic carbocyclylcarbonylamino”, “substituted or unsubstituted aromatic heterocyclylcarbonylamino”, and “substituted or unsubstituted non-aromatic heterocyclylcarbonylamino”,
“substituted or unsubstituted aromatic carbocyclylsulfonylamino”, “substituted or unsubstituted non-aromatic carbocyclylsulfonylamino”, “substituted or unsubstituted aromatic heterocyclylsulfonylamino”, and “substituted or unsubstituted non-aromatic heterocyclyl sulfonyl amino”, and
“substituted or unsubstituted aromatic carbocyclyloxycarbonylamino”, “substituted or unsubstituted non-aromatic carbocyclyloxycarbonylamino”, “substituted or unsubstituted aromatic heterocyclyloxycarbonylamino”, and “substituted or unsubstituted non-aromatic heterocyclyloxycarbonylamino” in R.sup.9a and R.sup.9b include, for example, halogen, hydroxy, carboxy, amino, carbamoyl, sulfamoyl, sulfo, cyano, alkyl optionally substituted with one or more group(s) selected from the substituent, group D, alkyloxy optionally substituted with one or more group(s) selected from the substituent group D, alkylamino optionally substituted with one or more group (s) selected from the substituent group D, alkylsulfanyl optionally substituted with one or more group(s) selected from the substituent group D, alkylcarbonyl optionally substituted with one or more group(s) selected from the substituent group D, alkylsulfonyl optionally substituted with one or more group(s) selected from the substituent group D, alkylcarbonylamino optionally substituted with one or more group(s) selected from the substituent group D, alkylsulfonylamino optionally substituted with one or more group(s) selected from the substituent group D, alkylcarbamoyl optionally substituted with one or more group(s) selected from the substituent group D, alkylsulfamoyl optionally substituted with one or more group(s) selected from the substituent group D and the like.

(269) One embodiment is, for example, halogen, hydroxy, cyano, alkyl optionally substituted with one or more group(s) selected from the substituent group D, alkyloxy optionally substituted with one or more group(s) selected from the substituent group D, alkylamino optionally substituted with one or more group(s) selected from the substituent group D, alkylsulfanyl optionally substituted with one or more group(s) selected from the substituent group D or the like.

(270) One embodiment, is, for example, halogen, alkyl optionally substituted with one or more group(s) selected from the substituent group D, alkyloxy optionally substituted with one or more group(s) selected from the substituent group D or the like.

(271) One embodiment is, for example, halogen, alkyl, haloalkyl, alkyloxy, haloalkyloxy or the like.

(272) One embodiment is, for example, halogen or the like.

(273) The substituents of “substituted or unsubstituted alkyl”, “substituted or unsubstituted alkenyl”, “substituted or unsubstituted alkynyl”, “substituted or unsubstituted alkyloxy”, “substituted or unsubstituted alkenyloxy”, “substituted or unsubstituted alkynyloxy”, “substituted or unsubstituted alkylsulfanyl”, “substituted or unsubstituted alkenylsulfinyl”, “substituted or unsubstituted alkynylsulfanyl”. “substituted or unsubstituted alkylamino”, “substituted or unsubstituted alkenylamino”, “substituted or unsubstituted alkynylamino”, “substituted or unsubstituted alkylcarbonyl”, “substituted or unsubstituted alkenylcarbonyl”, “substituted or unsubstituted alkynylcarbonyl”, “substituted or unsubstituted alkylsulfonyl”, “substituted or unsubstituted alkenylsulfonyl”, “substituted or unsubstituted alkynylsulfinyl”, “substituted or unsubstituted alkylcarbonyloxy”, “substituted or unsubstituted alkenylcarbonyloxy”, “substituted or unsubstituted alkynylcarbonyloxy”, “substituted or unsubstituted alkyloxycarbonyl”, “substituted or unsubstituted alkenyloxycarbonyl”, “substituted or unsubstituted alkynyloxycarbonyl”, “substituted or unsubstituted alkylsulfonyloxy”, “substituted or unsubstituted alkenylsulfonyloxy”, “substituted or unsubstituted alkynylsulfonyloxy”, “substituted or unsubstituted aryloxysulfonyl”, “substituted or unsubstituted alkenyloxysulfonyl”, “substituted or unsubstituted alkynyloxysulfonyl”, “substituted or unsubstituted alkylcarbamoyl”, “substituted or unsubstituted alkenylcarbamoyl”, “substituted or unsubstituted alkynylcarbamoyl”, “substituted or unsubstituted alkylsulfamoyl”, “substituted or unsubstituted alkenylsulfamoyl”, “substituted or unsubstituted alkynylsulfamoyl”, “substituted or unsubstituted alkylcarbonylamino”, “substituted or unsubstituted alkenylcarbonylamino”, “substituted or unsubstituted alkynylcarbonylamino”, “substituted or unsubstituted alkylsulfonylamino”, “substituted or unsubstituted alkenylsulfonylamino”, “substituted or unsubstituted alkyloxycarbonylamino”, “substituted or unsubstituted alkenyloxycarbonylamino”, and “substituted or unsubstituted alkyloxycarbonylamino” in R.sup.10a, R.sup.10aa, R.sup.10ab, R.sup.10ac, R.sup.10b, R.sup.10c and R.sup.10d include, for example, halogen, hydroxy, carboxy, amino, carbamoyl, sulfamoyl, sulfo, cyano, alkyloxy optionally substituted with one or more group(s) selected from the substituent group D, alkylamino optionally substituted with one or more group(s) selected from the substituent group D, alkylsulfanyl optionally substituted with one or more group(s) selected from the substituent group D, alkylcarbonyl optionally substituted with one or more group(s) selected from the substituent group D, alkylsulfonyl optionally substituted with one or more group(s) selected from the substituent group D, alkylcarbonylamino optionally substituted with one or more group(s) selected from the substituent group D, alkylsulfonylamino optionally substituted with one or more group(s) selected from the substituent group D, alkylcarbamoyl optionally substituted with one or more group(s) selected from the substituent group D, alkylsulfamoyl optionally substituted with one or more group(s) selected from the substituent group D, aromatic carbocyclyl optionally substituted with one or more group(s) selected from the substituent, group F, non-aromatic carbocyclyl optionally substituted with one or more group(s) selected from the substituent group F, aromatic heterocyclyl optionally substituted with one or more group(s) selected from the substituent group F, non-aromatic heterocyclyl optionally substituted with one or more group(s) selected from the substituent group F, aromatic carbocyclyloxy optionally substituted with one or more group(s) selected from the substituent group F, non-aromatic carbocyclyloxy optionally substituted with one or more group(s) selected from the substituent group F, aromatic heterocyclyloxy optionally substituted with one or more group(s) selected from the substituent group F, non-aromatic heterocyclyloxy optionally substituted with one or more group(s) selected from the substituent group F, aromatic carbocyclylsulfanyl optionally substituted with one or more group(s) selected from the substituent group F, non-aromatic carbocyclylsulfanyl optionally substituted with one or more group(s) selected from the substituent group F, aromatic heterocyclylsulfanyl optionally substituted with one or more group(s) selected from the substituent group F, non-aromatic heterocyclylsulfanyl optionally substituted with one or more group(s) selected from the substituent group F, aromatic carbocyclylamino optionally substituted with one or more group(s) selected from the substituent group F, non-aromatic carbocyclylamino optionally substituted with one or more group(s) selected from the substituent group F, aromatic heterocyclylamino optionally substituted with one or more group(s) selected from the substituent group F, and non-aromatic heterocyclylamino optionally substituted with one or more group(s) selected from the substituent group F and the like.

(274) One embodiment is, for example, halogen, hydroxy, carboxy, amino, carbamoyl, sulfamoyl, sulfo, cyano, alkyloxy optionally substituted with one or more group(s) selected from the substituent group D, alkylamino optionally substituted with one or more group(s) selected from the substituent group D, alkylsulfanyl optionally substituted with one or more group(s) selected from the substituent group D, aromatic carbocyclyl optionally substituted with one or more group(s) selected from the substituent, group F, non-aromatic carbocyclyl optionally substituted with one or more group (s) selected from the substituent, group F, aromatic heterocyclyl optionally substituted with one or more group(s) selected from the substituent, group F, non-aromatic heterocyclyl optionally substituted with one or more group(s) selected from the substituent group F or the like.

(275) One embodiment, is, for example, halogen, hydroxy, cyano, alkyloxy optionally substituted with one or more group(s) selected from the substituent group D, aromatic carbocyclyl optionally substituted with one or more group(s) selected from the substituent group F, non-aromatic carbocyclyl optionally substituted with one or more group(s) selected from the substituent group F, aromatic heterocyclyl optionally substituted with one or more group(s) selected from the substituent, group F, non-aromatic heterocyclyl optionally substituted with one or more group(s) selected from the substituent group F or the like.

(276) One embodiment is, for example, halogen, hydroxy, alkyloxy, haloalkyloxy, aromatic carbocyclyl optionally substituted with one or more group(s) selected from the substituent group F, non-aromatic carbocyclyl optionally substituted with one or more group(s) selected from the substituent group F, aromatic heterocyclyl optionally substituted with one or more group(s) selected from the substituent group F, non-aromatic heterocyclyl optionally substituted with one or more group(s) selected from the substituent, group F or the like.

(277) One embodiment is, for example, halogen, hydroxy, alkyloxy optionally substituted with one or more group(s) selected from the substituent group D, non-aromatic heterocyclyl optionally substituted with one or more group(s) selected from the substituent group F or the like.

(278) One embodiment is, for example, halogen, hydroxy, alkyloxy, haloalkyloxy, aromatic carbocyclyl, non-aromatic carbocyclyl, aromatic heterocyclyl, non-aromatic heterocyclyl or the like.

(279) One embodiment is, for example, halogen, hydroxy, alkyloxy, non-aromatic heterocyclyl or the like.

(280) One embodiment is, for example, halogen, hydroxy, alkyloxy or the like.

(281) The substituents on the rings of “aromatic carbocycle”, “non-aromatic carbocycle”, “aromatic heterocycle”, and “non-aromatic heterocycle” of “substituted or unsubstituted aromatic carbocyclyl”, “substituted or unsubstituted non-aromatic carbocyclyl”, “substituted or unsubstituted aromatic heterocyclyl”, and “substituted or unsubstituted non-aromatic heterocyclyl”,

(282) “substituted or unsubstituted aromatic carbocyclyloxy”, “substituted or unsubstituted non-aromatic carbocyclyloxy”, “substituted or unsubstituted aromatic heterocyclyloxy”, and “substituted or unsubstituted non-aromatic heterocyclyloxy”, “substituted or unsubstituted aromatic carbocyclylamino”, “substituted or unsubstituted non-aromatic carbocyclylamino”, “substituted or unsubstituted aromatic heterocyclylamino”, and “substituted or unsubstituted non-aromatic heterocyclylamino”,
“substituted or unsubstituted aromatic carbocyclylsulfanyl”, “substituted or unsubstituted non-aromatic carbocyclylsulfanyl”, “substituted or unsubstituted aromatic heterocyclyl sulfanyl”, and “substituted or unsubstituted non-aromatic heterocyclylsulfanyl”,
“substituted or unsubstituted aromatic carbocyclylcarbonyl”, “substituted or unsubstituted non-aromatic carbocyclylcarbonyl”, “substituted or unsubstituted aromatic heterocyclylcarbonyl”, and “substituted or unsubstituted non-aromatic heterocyclylcarbonyl”,
“substituted or unsubstituted aromatic carbocyclylsulfonyl”, “substituted or unsubstituted non-aromatic carbocyclylsulfonyl”, “substituted or unsubstituted aromatic heterocyclylsulfonyl”, and “substituted or unsubstituted non-aromatic heterocyclylsulfonyl”,
“substituted or unsubstituted aromatic carbocyclylcarbonyloxy”, “substituted or unsubstituted non-aromatic carbocyclylcarbonyloxy”, “substituted or unsubstituted aromatic heterocyclylcarbonyloxy”, and “substituted or unsubstituted non-aromatic heterocyclylcarbonyloxy”,
“substituted or unsubstituted aromatic carbocyclyloxycarbonyl”, “substituted or unsubstituted non-aromatic carbocyclyloxycarbonyl”, “substituted or unsubstituted aromatic heterocyclyloxycarbonyl”, and “substituted or unsubstituted non-aromatic heterocyclyloxycarbonyl”,
“substituted or unsubstituted aromatic carbocyclylsulfonyloxy”, “substituted or unsubstituted non-aromatic carbocyclylsulfonyloxy”, “substituted or unsubstituted aromatic heterocyclylsulfonyloxy”, and “substituted or unsubstituted non-aromatic heterocyclylsulfonyloxy”,
“substituted or unsubstituted aromatic carbocyclyloxysulfonyl”, “substituted or unsubstituted non-aromatic carbocyclyloxysulfonyl”, “substituted or unsubstituted aromatic heterocyclyloxysulfonyl”, and “substituted or unsubstituted non-aromatic heterocyclyloxysulfonyl”,
“substituted or unsubstituted aromatic carbocyclylcarbamoyl”, “substituted or unsubstituted non-aromatic carbocyclylcarbamoyl”, “substituted or unsubstituted aromatic heterocyenylcarbamoyl”, and “substituted or unsubstituted non-aromatic heterocyclylcarbamoyl”.
“substituted or unsubstituted aromatic carbocyclylsulfamoyl”, “substituted or unsubstituted non-aromatic carbocyclylsulfamoyl”, “substituted or unsubstituted aromatic heterocyclylsulfamoyl”, and “substituted or unsubstituted non-aromatic heterocyclylsulfamoyl”,
“substituted or unsubstituted aromatic carbocyclylcarbonylamino”, “substituted or unsubstituted non-aromatic carbocyclylcarbonylamino”, “substituted or unsubstituted aromatic heterocyclylcarbonylamino”, and “substituted or unsubstituted non-aromatic heterocyclylcarbonylamino”,
“substituted or unsubstituted aromatic carbocyclylsulfonylamino”, “substituted or unsubstituted non-aromatic carbocyclylsulfonylamino”, “substituted or unsubstituted aromatic heterocyclylsulfonylamino”, and “substituted or unsubstituted non-aromatic heterocyclylsulfonylamino”, and
“substituted or unsubstituted aromatic carbocyclyloxycarbonylamino”, “substituted or unsubstituted non-aromatic carbocyclyloxycarbonylamino”, “substituted or unsubstituted aromatic heterocyclyloxycarbonyl amino”, and “substituted or unsubstituted non-aromatic heterocyclyloxycarbonylamino” in R.sup.10a, R.sup.10aa, R.sup.10ab, R.sup.10ac, R.sup.10b, R.sup.10c and R.sup.10d include, for example, halogen, hydroxy, carboxy, amino, carbamoyl, sulfamoyl, sulfo, cyano, alkyl optionally substituted with one or more group(s) selected from the substituent group D, alkyloxy optionally substituted with one or more group(s) selected from the substituent group D, alkylamino optionally substituted with one or more group(s) selected from the substituent, group D, alkylsulfanyl optionally substituted with one or more group(s) selected from the substituent group D, alkylcarbonyl optionally substituted with one or more group(s) selected from the substituent group D, alkylsulfonyl optionally substituted with one or more group(s) selected from the substituent group D, alkylcarbonylamino optionally substituted with one or more group(s) selected from the substituent, group D, alkylsulfonylamino optionally substituted with one or more group(s) selected from the substituent group D, alkylcarbamoyl optionally substituted with one or more group(s) selected from the substituent group D, alkylsulfamoyl optionally substituted with one or more group(s) selected from the substituent group D and the like.

(283) One embodiment is, for example, halogen, hydroxy, carboxy, amino, carbamoyl, sulfamoyl, sulfo, cyano, alkyl optionally substituted with one or more group(s) selected from the substituent group D, alkyloxy optionally substituted with one or more group(s) selected from the substituent group D, alkylamino optionally substituted with one or more group(s) selected from the substituent group D, alkylsulfanyl optionally substituted with one or more group(s) selected from the substituent group D or the like.

(284) One embodiment is, for example, halogen, alkyl optionally substituted with one or more group(s) selected from the substituent group D, alkyloxy optionally substituted with one or more group(s) selected from the substituent group D or the like.

(285) One embodiment, is, for example, halogen, alkyl, haloalkyl, alkyloxy, haloalkyloxy or the like.

(286) One embodiment is, for example, halogen, alkyl, haloalkyl or the like.

(287) One embodiment is, for example, halogen, alkyl or the like.

(288) The substituents of “substituted or unsubstituted alkyl”, and “substituted or unsubstituted alkyloxy” in R.sup.10c include, for example, halogen, hydroxy, carboxy, amino, carbamoyl, sulfamoyl, sulfo, cyano and the like.

(289) One embodiment is, for example, halogen, hydroxy, cyano or the like.

(290) One embodiment is, for example, halogen or the like.

(291) The substituents on the rings of “substituted or unsubstituted aromatic carbocycle”, “substituted or unsubstituted non-aromatic carbocycle”, “substituted or unsubstituted aromatic heterocycle”, and “substituted or unsubstituted non-aromatic heterocycle” when

(292) “R.sup.9a and R.sup.10a which an; attached to the adjacent atoms, or R.sup.9b and R.sup.10b which are attached to the adjacent atoms are taken together to form a substituted or unsubstituted aromatic carbocycle, a substituted or unsubstituted non-aromatic carbocycle, a substituted or unsubstituted aromatic heterocycle, or a substituted or unsubstituted non-aromatic heterocycle”,
“R.sup.11c is taken together with R.sup.9a which is attached to the adjacent atom to form a substituted or unsubstituted aromatic carbocycle, a substituted or unsubstituted non-aromatic carbocycle, a substituted or unsubstituted aromatic heterocycle, or a substituted or unsubstituted non-aromatic heterocycle”, and
“R.sup.11c is taken together with R.sup.9a which is attached to the adjacent atoms to form a substituted or unsubstituted aromatic carbocycle, a substituted or unsubstituted non-aromatic carbocycle, a substituted or unsubstituted aromatic heterocycle, or a substituted or unsubstituted non-aromatic heterocycle,
and
the substituents on the rings of “substituted or unsubstituted 5-membered non-aromatic carbocycle”, “substituted or unsubstituted 5-membered aromatic heterocycle”, “substituted or unsubstituted 5-membered non-aromatic heterocycle”, “substituted or unsubstituted 6-membered aromatic carbocycle”, “substituted or unsubstituted 6-membered non-aromatic carbocycle”, “substituted or unsubstituted 6-membered aromatic heterocycle” and “substituted or unsubstituted 6-membered non-aromatic heterocycle” in Ring F3, Ring G3, and Ring H2 include,
for example, halogen, hydroxy, carboxy, amino, carbamoyl, sulfamoyl, sulfo, cyano, alkyl optionally substituted with one or more group(s) selected from the substituent group D, alkyloxy optionally substituted with one or more group(s) selected from the substituent group D, alkylamino optionally substituted with one or more group(s) selected from the substituent group D, alkylsulfanyl optionally substituted with one or more group(s) selected from the substituent, group D, alkylcarbonyl optionally substituted with one or more group(s) selected from the substituent group D, alkylsulfonyl optionally substituted with one or more group(s) selected from the substituent group D, alkylcarbonylamino optionally substituted with one or more group(s) selected from the substituent group D, alkylsulfonylamino optionally substituted with one or more group(s) selected from the substituent group D, alkylcarbamoyl optionally substituted with one or more group(s) selected from the substituent group D, alkylsulfamoyl optionally substituted with one or more group(s) selected from the substituent group D and the like.

(293) One embodiment is, for example, halogen, hydroxy, carboxy, amino, carbamoyl, sulfamoyl, sulfo, cyano, alkyl optionally substituted with one or more group(s) selected from the substituent group D, alkyloxy optionally substituted with one or more group(s) selected from the substituent group D, alkylamino optionally substituted with one or more group(s) selected from the substituent group D, alkylsulfanyl optionally substituted with one or more group(s) selected from the substituent, group D, alkylcarbonyl optionally substituted with one or more group(s) selected from the substituent group D, alkylsulfonyl optionally substituted with one or more group(s) selected from the substituent group D, alkylcarbonylamino optionally substituted with one or more group(s) selected from the substituent group D, alkylsulfonylamino optionally substituted with one or more group(s) selected from the substituent group D, alkylcarbamoyl optionally substituted with one or more group(s) selected from the substituent group D, alkylsulfamoyl optionally substituted with one or more group(s) selected from the substituent group D, alkylcarbonyloxy optionally substituted with one or more group(s) selected from the substituent group D, alkyloxycarbonyl optionally substituted with one or more group(s) selected from the substituent, group D, alkylsulfonyloxy optionally substituted with one or more group(s) selected from the substituent group D, aryloxysulfonyl optionally substituted with one or more group(s) selected from the substituent group D, aromatic carbocyclyl optionally substituted with one or more group(s) selected from the substituent group F, non-aromatic carbocyclyl optionally substituted with one or more group(s) selected from the substituent group F, aromatic heterocyclyl optionally substituted with one or more group(s) selected from the substituent group F, non-aromatic heterocyclyl optionally substituted with one or more group(s) selected from the substituent group F or the like.

(294) One embodiment is, for example, halogen, hydroxy, carboxy, amino, carbamoyl, sulfamoyl, sulfo, cyano, alkyl optionally substituted with one or more group(s) selected from the substituent group D, alkyloxy optionally substituted with one or more group(s) selected from the substituent group D, alkylamino optionally substituted with one or more group(s) selected from the substituent group D, alkylsulfanyl optionally substituted with one or more group(s) selected from the substituent group D or the like.

(295) One embodiment is, for example, halogen, alkyl optionally substituted with one or more group(s) selected from the substituent group D, alkyloxy optionally substituted with one or more group(s) selected from the substituent group D or the like.

(296) One embodiment is, for example, halogen, alkyl, haloalkyl, alkyloxy, haloalkyloxy or the like.

(297) One embodiment is, for example, halogen, alkyl or the like.

(298) One embodiment is, for example, halogen, hydroxy, alkyl optionally substituted with one or more group(s) selected from the substituent group D, alkyloxy optionally substituted with one or more group(s) selected from the substituent group D, alkyloxycarbonyl optionally substituted with one or more group(s) selected from the substituent group D, aromatic carbocyclyl optionally substituted with one or more group(s) selected from the substituent group F, non-aromatic carbocyclyl optionally substituted with one or more group(s) selected from the substituent group F, aromatic heterocyclyl optionally substituted with one or more group(s) selected from the substituent group F, non-aromatic heterocyclyl optionally substituted with one or more group(s) selected from the substituent group F or the like.

(299) One embodiment is, for example, halogen, hydroxy, alkyl optionally substituted with one or more group(s) selected from the substituent group D, alkyloxycarbonyl optionally substituted with one or more group(s) selected from the substituent group D, aromatic carbocyclyl optionally substituted with one or more group(s) selected from the substituent group F or the like.

(300) One embodiment is, for example, halogen, hydroxy, alkyl, alkyloxyoxycarbonyl, aromatic carbocyclyl or the like.

(301) The substituents on the rings of “substituted or unsubstituted aromatic carbocycle”, “substituted or unsubstituted non-aromatic carbocycle”, “substituted or unsubstituted aromatic heterocycle”, and “substituted or unsubstituted non-aromatic heterocycle” when

(302) “two R.sup.10a which are attached to the adjacent atoms, or two R.sup.10b which are attached to the adjacent atoms are taken together to form a substituted or unsubstituted aromatic carbocycle, a substituted or unsubstituted non-aromatic carbocycle, a substituted or unsubstituted aromatic heterocycle, or a substituted or unsubstituted non-aromatic heterocycle”,
“R.sup.11c is taken together with which is attached to the adjacent atom to form a substituted or unsubstituted aromatic carbocycle, a substituted or unsubstituted non-aromatic carbocycle, a substituted or unsubstituted aromatic heterocycle, or a substituted or unsubstituted non-aromatic heterocycle”, and
“R.sup.11d is taken together with R.sup.11bb which is attached to the adjacent atoms to form a substituted or unsubstituted aromatic carbocycle, a substituted or unsubstituted non-aromatic carbocycle, a substituted or unsubstituted aromatic heterocycle, or a substituted or unsubstituted non-aromatic heterocycle”, and
the substituents on the rings of “substituted or unsubstituted 5-membered non-aromatic carbocycle”, “substituted or unsubstituted 5-membered aromatic heterocycle”, “substituted or unsubstituted 5-membered non-aromatic, heterocycle”, “substituted or unsubstituted 6-membered aromatic carbocycle”, “substituted or unsubstituted 6-membered non-aromatic carbocycle”, “substituted or unsubstituted 6-membered aromatic heterocycle” and “substituted or unsubstituted 6-membered non-aromatic heterocycle” in Ring F1, Ring F2, Ring G1, Ring G2, and Ring H1 include, for example, halogen, hydroxy, carboxy, amino, carbamoyl, sulfamoyl, sulfo, cyano, alkyl optionally substituted with one or more group(s) selected from the substituent group D, alkyloxy optionally substituted with one or more group(s) selected from the substituent group D, alkylamino optionally substituted with one or more group(s) selected from the substituent group D, alkylsulfanyl optionally substituted with one or more group(s) selected from the substituent group D, alkylcarbonyl optionally substituted with one or more group(s) selected from the substituent group D, alkylsulfonyl optionally substituted with one or more group(s) selected from the substituent, group D, alkylcarbonylamino optionally substituted with one or more group(s) selected from the substituent group D, alkylsulfonylamino optionally-substituted with one or more group(s) selected from the substituent group D, alkylcarbamoyl optionally substituted with one or more group(s) selected from the substituent, group D, alkylsulfamoyl optionally substituted with one or more group(s) selected from the substituent group D and the like.

(303) One embodiment is, for example, halogen, hydroxy, carboxy, amino, carbamoyl, sulfamoyl, sulfo, cyano, alkyl optionally substituted with one or more group(s) selected from the substituent group D, alkyloxy optionally substituted with one or more group(s) selected from the substituent, group D, alkylamino optionally substituted with one or more group(s) selected from the substituent group D, alkylsulfanyl optionally substituted with one or more group(s) selected from the substituent group D or the like.

(304) One embodiment is, for example, halogen, alkyl optionally substituted with one or more group(s) selected from the substituent group D, alkyloxy optionally substituted with one or more group(s) selected from the substituent group D or the like.

(305) One embodiment is, for example, halogen, alkyl, haloalkyl, alkyloxy, haloalkyloxy or the like.

(306) One embodiment is, for example, halogen, alkyl, haloalkyl, alkyloxy or the like.

(307) The substituents of “substituted or unsubstituted alkyl”, “substituted or unsubstituted alkenyl”, “substituted or unsubstituted alkynyl”, “substituted or unsubstituted alkyloxy”, “substituted or unsubstituted alkenyloxy”, “substituted or unsubstituted alkynyloxy”, “substituted or unsubstituted alkylsulfanyl”, “substituted or unsubstituted alkenylsulfanyl”, “substituted or unsubstituted alkynyl sulfanyl”, “substituted or unsubstituted alkylamino”, “substituted or unsubstituted alkenylamino”, “substituted or unsubstituted alkynylamino”, “substituted or unsubstituted alkylcarbonyl”, “substituted or unsubstituted alkenylcarbonyl”, “substituted or unsubstituted alkynylcarbonyl”, “substituted or unsubstituted alkylsulfonyl”, “substituted or unsubstituted alkenylsulfonyl”, “substituted or unsubstituted alkynylsulfonyl”, “substituted or unsubstituted alkylcarbonyloxy”, “substituted or unsubstituted alkenylcarbonyloxy”, “substituted or unsubstituted alkynylcarbonyloxy”, “substituted or unsubstituted alkyloxycarbonyl”, “substituted or unsubstituted alkenyloxycarbonyl”, “substituted or unsubstituted alkynyloxycarbonyl”, “substituted or unsubstituted alkylsulfonyloxy”, “substituted or unsubstituted alkenylsulfonyloxy”, “substituted or unsubstituted alkynylsulfonyloxy”, “substituted or unsubstituted aryloxysulfonyl”, “substituted or unsubstituted alkenyloxysulfonyl”, “substituted or unsubstituted alkynyloxysulfonyl”, “substituted or unsubstituted alkylcarbamoyl”, “substituted or unsubstituted alkenylcarbamoyl”, “substituted or unsubstituted alkynylcarbamoyl”, “substituted or unsubstituted alkylsulfamoyl”, “substituted or unsubstituted alkenylsulfamoyl”, “substituted or unsubstituted alkynylsulfamoyl”, “substituted or unsubstituted alkylcarbonylamino”, “substituted or unsubstituted alkenylcarbonylamino”, “substituted or unsubstituted alkynylcarbonylamino”, “substituted or unsubstituted alkylsulfonylamino”, “substituted or unsubstituted alkenylsulfonylamino”, “substituted or unsubstituted alkyloxycarbonylamino”, “substituted or unsubstituted alkenyloxycarbonylamino”, and “substituted or unsubstituted alkynyloxycarbonylamino” in R.sup.11a and R.sup.11b include, for example, halogen, hydroxy, carboxy, amino, carbamoyl, sulfamoyl, sulfo, cyano, alkyloxy optionally substituted with one or more group(s) selected from the substituent group D, alkylamino optionally substituted with one or more group(s) selected from the substituent group D, alkylsulfanyl optionally substituted with one or more group(s) selected from the substituent group D, alkylcarbonyl optionally substituted with one or more group(s) selected from the substituent group D, alkylsulfonyl optionally substituted with one or more group(s) selected from the substituent group D, alkylcarbonylamino optionally substituted with one or more group(s) selected from the substituent group D, alkylsulfonylamino optionally substituted with one or more group(s) selected from the substituent group D, alkylcarbamoyl optionally substituted with one or more group(s) selected from the substituent group D, alkylsulfamoyl optionally substituted with one or more group(s) selected from the substituent group D, aromatic carbocyclyl optionally substituted with one or more group(s) selected from the substituent group F, non-aromatic carbocyclyl optionally substituted with one or more group(s) selected from the substituent group F, aromatic heterocyclyl optionally substituted with one or more group(s) selected from the substituent group F, non-aromatic heterocyclyl optionally substituted with one or more group(s) selected from the substituent, group F, aromatic carbocyclyloxy optionally substituted with one or more group(s) selected from the substituent group F, non-aromatic carbocyclyloxy optionally substituted with one or more group(s) selected from the substituent group F, aromatic heterocyclyloxy optionally substituted with one or more group(s) selected from the substituent group F, non-aromatic heterocyclyloxy optionally substituted with one or more group(s) selected from the substituent group F, aromatic carbocyclylsulfanyl optionally substituted with one or more group(s) selected from the substituent group F, non-aromatic carbocyclylsulfanyl optionally substituted with one or more group(s) selected from the substituent group F, aromatic heterocyclylsulfanyl optionally substituted with one or more group(s) selected from the substituent group F, non-aromatic heterocyclylsulfanyl optionally substituted with one or more group(s) selected from the substituent group F, aromatic carbocyclylamino optionally substituted with one or more group(s) selected from the substituent group F, non-aromatic carbocyclylamino optionally substituted with one or more group(s) selected from the substituent group F, aromatic heterocyclylamino optionally substituted with one or more group(s) selected from the substituent group F, and non-aromatic heterocyclylamino optionally substituted with one or more group(s) selected from the substituent group F and the like.

(308) One embodiment is, for example, halogen, hydroxy, carboxy, amino, carbamoyl, sulfamoyl, sulfo, cyano, alkyloxy optionally substituted with one or more group(s) selected from the substituent, group D, alkylamino optionally substituted with one or more group(s) selected from the substituent group D, alkylsulfanyl optionally substituted with one or more group(s) selected from the substituent, group D or the like.

(309) One embodiment is, for example, halogen, hydroxy, cyano or the like.

(310) One embodiment is, for example, halogen or the like.

(311) The substituents on the rings of “aromatic carbocycle”, “non-aromatic carbocycle”, “aromatic heterocycle”, and “non-aromatic heterocycle” of “substituted or unsubstituted aromatic carbocyclyl”, “substituted or unsubstituted non-aromatic carbocyclyl”, “substituted or unsubstituted aromatic heterocyclyl”, and “substituted or unsubstituted non-aromatic heterocyclyl”,

(312) “substituted or unsubstituted aromatic carbocyclyloxy”, “substituted or unsubstituted non-aromatic carbocyclyloxy”, “substituted or unsubstituted aromatic, heterocyclyloxy”, and “substituted or unsubstituted non-aromatic, heterocyclyloxy”, “substituted or unsubstituted aromatic carbocyclylamino”, “substituted or unsubstituted non-aromatic carbocyclylamino”, “substituted or unsubstituted aromatic heterocyclylamino”, and “substituted or unsubstituted non-aromatic heterocyclylamino”,
“substituted or unsubstituted aromatic carbocyclylsulfanyl”, “substituted or unsubstituted non-aromatic carbocyclylsulfanyl”, “substituted or unsubstituted aromatic heterocyclylsulfanyl”, and “substituted or unsubstituted non-aromatic heterocyclylsulfanyl”,
“substituted or unsubstituted aromatic carbocyclylcarbonyl”, “substituted or unsubstituted non-aromatic carbocyclylcarbonyl”, “substituted or unsubstituted aromatic heterocyclylcarbonyl”, and “substituted or unsubstituted non-aromatic heterocyclylcarbonyl”,
“substituted or unsubstituted aromatic carbocyclylsulfonyl”, “substituted or unsubstituted non-aromatic carbocyclylsulfonyl”, “substituted or unsubstituted aromatic heterocyclylsulfonyl”, and “substituted or unsubstituted non-aromatic heterocyclylsulfonyl”,
“substituted or unsubstituted aromatic carbocyclylcarbonyloxy”, “substituted or unsubstituted non-aromatic carbocyclylcarbonyloxy”, “substituted or unsubstituted aromatic heterocyclylcarbonyloxy”, and “substituted or unsubstituted non-aromatic heterocyclylcarbonyloxy”,
“substituted or unsubstituted aromatic carbocyclyloxycarbonyl”, “substituted or unsubstituted non-aromatic carbocyclyloxycarbonyl”, “substituted or unsubstituted aromatic heterocyclyloxycarbonyl”, and “substituted or unsubstituted non-aromatic heterocyclyloxycarbonyl”,
“substituted or unsubstituted aromatic carbocyclylsulfonyloxy”, “substituted or unsubstituted non-aromatic carbocyclylsulfonyloxy”, “substituted or unsubstituted aromatic heterocyclylsulfonyloxy”, and “substituted or unsubstituted non-aromatic heterocyclylsulfonyloxy”,
“substituted or unsubstituted aromatic carbocyclyloxysulfonyl”, “substituted or unsubstituted non-aromatic carbocyclyloxysulfonyl”, “substituted or unsubstituted aromatic heterocyclyloxysulfonyl”, and “substituted or unsubstituted non-aromatic heterocyclyloxysulfonyl”.
“substituted or unsubstituted aromatic carbocyclylcarbamoyl”, “substituted or unsubstituted non-aromatic carbocyclylcarbamoyl”, “substituted or unsubstituted aromatic heterocyclylcarbamoyl”, and “substituted or unsubstituted non-aromatic heterocyclylcarbamoyl”,
“substituted or unsubstituted aromatic carbocyclylsulfamoyl”, “substituted or unsubstituted non-aromatic carbocyclylsulfamoyl”, “substituted or unsubstituted aromatic heterocycylsulfamoyl”, and “substituted or unsubstituted non-aromatic heterocyclylsulfamoyl”,
“substituted or unsubstituted aromatic carbocyclylcarbonylamino”, “substituted or unsubstituted non-aromatic carbocyclylcarbonylamino”, “substituted or unsubstituted aromatic heterocyclylcarbonylamino”, and “substituted or unsubstituted non-aromatic heterocyclylcarbonyl amino”,
“substituted or unsubstituted aromatic carbocyclylsulfonylamino”, “substituted or unsubstituted non-aromatic carbocyclylsulfonylamino”, “substituted or unsubstituted aromatic heterocyclylsulfonylamino”, and “substituted or unsubstituted non-aromatic heterocyclylsulfonylamino”, and
“substituted or unsubstituted aromatic carbocyclyloxycarbonyl amino”, “substituted or unsubstituted non-aromatic carbocyclyloxycarbonylamino”, “substituted or unsubstituted aromatic heterocyclyloxycarbonylamino”, and “substituted or unsubstituted non-aromatic heterocyclyloxycarbonylamino” in R.sup.10a1, R.sup.10a2, R.sup.10b1, R.sup.11a and R.sup.11b include, for example, halogen, hydroxy, carboxy, amino, carbamoyl, sulfamoyl, sulfo, cyano, alkyl optionally substituted with one or more group(s) selected from the substituent group D, alkyloxy optionally substituted with one or more group(s) selected from the substituent group D, alkylamino optionally substituted with one or more group(s) selected from the substituent group D, alkylsulfanyl optionally substituted with one or more group(s) selected from the substituent, group D, alkylcarbonyl optionally substituted with one or more group(s) selected from the substituent group D, alkylsulfonyl optionally substituted with one or more group(s) selected from the substituent group D, alkylcarbonylamino optionally substituted with one or more group(s) selected from the substituent group D, alkylsulfonylamino optionally substituted with one or more group(s) selected from the substituent group D, alkylcarbamoyl optionally substituted with one or more group(s) selected from the substituent group D, alkylsulfamoyl optionally substituted with one or more group(s) selected from the substituent group D and the like.

(313) One embodiment is, for example, halogen, hydroxy, carboxy, amino, carbamoyl, sulfamoyl, sulfo, cyano, alkyl optionally substituted with one or more group(s) selected from the substituent group D, alkyloxy optionally substituted with one or more group(s) selected from the substituent group D, alkylamino optionally substituted with one or more group(s) selected from the substituent group D, alkylsulfanyl optionally substituted with one or more group(s) selected from the substituent group D or the like.

(314) One embodiment is, for example, halogen, alkyl optionally substituted with one or more group(s) selected from the substituent group D, alkyloxy optionally substituted with one or more group(s) selected from the substituent group D or the like.

(315) One embodiment is, for example, halogen, alkyl, haloalkyl, alkyloxy, haloalkyloxy or the like.

(316) One embodiment is, for example, halogen, alkyl, haloalkyl or the like.

(317) One embodiment is, for example, halogen or the like.

(318) The substituents of “substituted or unsubstituted alkyl”, “substituted or unsubstituted alkenyl”, “substituted or unsubstituted alkynyl”, “substituted or unsubstituted alkyloxy”, “substituted or unsubstituted alkenyloxy”, and “substituted or unsubstituted alkynyloxy” in R.sup.Y include, for example, halogen, hydroxy, carboxy, amino, carbamoyl, sulfamoyl, sulfo, cyano, alkyloxy optionally substituted with one or more group(s) selected from the substituent group D, alkylamino optionally substituted with one or more group(s) selected from the substituent group D, alkylsulfanyl optionally substituted with one or more group(s) selected from the substituent group D, alkylcarbonyl optionally substituted with one or more group(s) selected from the substituent group D, alkylsulfonyl optionally substituted with one or more group(s) selected from the substituent group D, alkylcarbonylamino optionally substituted with one or more group(s) selected from the substituent group D, alkylsulfonylamino optionally substituted with one or more group(s) selected from the substituent group D, aromatic carbocyclyl optionally substituted with one or more group(s) selected from the substituent group F, non-aromatic carbocyclyl optionally substituted with one or more group(s) selected from the substituent group F, aromatic heterocyclyl optionally substituted with one or more group(s) selected from the substituent group F, non-aromatic heterocyclyl optionally substituted with one or more group(s) selected from the substituent group F and the like.

(319) One embodiment is, for example, halogen, hydroxy, carboxy, amino, carbamoyl, sulfamoyl, sulfo, cyano or the like.

(320) One embodiment, is, for example, halogen, hydroxy, cyano or the like.

(321) One embodiment is, for example, halogen.

(322) The substituents on the rings of “substituted or unsubstituted aromatic carbocyclyl”, “substituted or unsubstituted non-aromatic carbocyclyl”, “substituted or unsubstituted aromatic heterocyclyl”, and “substituted or unsubstituted non-aromatic heterocyclyl” in R.sup.Y include, for example, halogen, hydroxy, carboxy, amino, carbamoyl, sulfamoyl, sulfo, cyano, alkyl optionally substituted with one or more group(s) selected from the substituent group D, alkyloxy optionally substituted with one or more group(s) selected from the substituent group D, alkylamino optionally substituted with one or more group(s) selected from the substituent group D, alkylsulfanyl optionally substituted with one or more group(s) selected from the substituent, group D, alkylcarbonyl optionally substituted with one or more group(s) selected from the substituent group D, alkylsulfonyl optionally substituted with one or more group(s) selected from the substituent group D, alkylcarbonylamino optionally substituted with one or more group(s) selected from the substituent group D, alkylsulfonylamino optionally substituted with one or more group(s) selected from the substituent group D, alkylcarbamoyl optionally substituted with one or more group(s) selected from the substituent group D, alkylsulfamoyl optionally substituted with one or more group(s) selected from the substituent group D and the like.

(323) One embodiment is, for example, halogen, hydroxy, carboxy, amino, carbamoyl, sulfamoyl, sulfo, cyano, alkyl optionally substituted with one or more group(s) selected from the substituent, group D, alkyloxy optionally substituted with one or more group(s) selected from the substituent group D, alkylamino optionally substituted with one or more group(s) selected from the substituent group D, alkylsulfanyl optionally substituted with one or more group(s) selected from the substituent group D or the like.

(324) One embodiment is, for example, halogen, alkyl optionally substituted with one or more group(s) selected from the substituent group D, alkyloxy optionally substituted with one or more group(s) selected from the substituent, group D or the like.

(325) One embodiment is, for example, halogen, alkyl, haloalkyl, alkyloxy, haloalkyloxy or the like.

(326) One embodiment is, for example, halogen, alkyl, haloalkyl or the like.

(327) One embodiment, is, for example, halogen or the like.

(328) One aspect of the present invention is illustrated below.

(329) Specific examples of each substituent in the compound represented by Formula (I) or pharmaceutically acceptable salt thereof are shown below. All combinations of these specific examples are illustrated for the compound represented by Formula (I).

(330) (a)

(331) A compound according to any one of the following (a-1) to (a-3) or a pharmaceutically acceptable salt thereof. (a-1) The compound represented by formula (I) wherein X is N(R.sup.7a) or O, or pharmaceutically acceptable salt thereof. (a-2) The compound represented by formula (I) wherein X is N(R.sup.7a), or pharmaceutically acceptable salt thereof. (a-3) The compound represented by formula (I) wherein X is O, or pharmaceutically acceptable salt thereof, (b) A compound according to any one of the following (b-1) to (b-3) or a pharmaceutically acceptable salt thereof. (b-1) The compound of formula (I) or the above (a), wherein R.sup.7a is a hydrogen atom, or substituted or unsubstituted alkyl, or pharmaceutically acceptable salt thereof. (b-2) The compound of formula (I) or the above (a), wherein R.sup.7a is a hydrogen atom, alkyl, or haloalkyl, or pharmaceutically acceptable salt thereof. (b-3) The compound of formula (I) or the above (a), wherein R.sup.7a is a hydrogen atom, or pharmaceutically acceptable salt thereof. (e) A compound according to any one of the following (c-1) to (c-4) or a pharmaceutically acceptable salt thereof. (c-1) The compound of formula (I) or the above (a) or (b), wherein R.sup.8a and R.sup.8b are each independently a hydrogen atom, halogen or substituted or unsubstituted alkyl, or pharmaceutically acceptable salt thereof. (c-2) The compound of formula (I) or the above (a) or (b), wherein R.sup.8a and R.sup.8b are each independently a hydrogen atom, halogen, alkyl, or haloalkyl, or pharmaceutically acceptable salt thereof. (c-3) The compound of formula (I) or the above (a) or (b) wherein R.sup.8a and R.sup.8b are each independently a hydrogen atom, or halogen, or pharmaceutically acceptable salt thereof. (c-4) The compound of formula (I) or the above (a) or (b) wherein each of R.sup.8a and R.sup.8b is a hydrogen atom, or pharmaceutically acceptable salt thereof. (d) A compound according to any one of the following (d-1) to (d-7) or a pharmaceutically acceptable salt thereof. (d-1) The compound of any one of formula (I) and the above (a) to (c), wherein

(332) ##STR00040##
or pharmaceutically acceptable salt thereof. (d-2) The compound of any one of formula (I) and the above (a) to (c), wherein

(333) ##STR00041##
or pharmaceutically acceptable salt thereof. (d-3) The compound of any one of formula (I) and the above (a) to (c), wherein

(334) ##STR00042##
or pharmaceutically acceptable salt thereof. (d-4) The compound of any one of formula (I) and the above (a) to (c), wherein

(335) ##STR00043##
or pharmaceutically acceptable salt thereof. (d-5) The compound of any one of formula (I) and the above (a) to (c), wherein

(336) ##STR00044##
or pharmaceutically acceptable salt thereof. (d-6) The compound of any one of formula (I) and the above (a) to (c), wherein

(337) ##STR00045##
or pharmaceutically acceptable salt thereof. (d-7) The compound of any one of formula (I) and the above (a) to (c), wherein

(338) ##STR00046##
or pharmaceutically acceptable salt thereof. (e) A compound according to any one of the following (e-1) to (e-37) or a pharmaceutically acceptable salt thereof. (e-1) The compound of any one of formula (I) and the above (a) to (d), wherein R.sup.1 is substituted or unsubstituted 6- to 10-membered aromatic carbocyclyl, substituted or unsubstituted 3- to 10-membered non-aromatic carbocyclyl, substituted or unsubstituted 5- to 10-membered aromatic heterocyclyl, or substituted or unsubstituted 3- to 10-membered non-aromatic heterocyclyl, or pharmaceutically acceptable salt thereof. (e-2) The compound of any one of formula (I) and the above (a) to (d), wherein R.sup.1 is substituted or unsubstituted 6-membered aromatic carbocyclyl, substituted or unsubstituted 3- to 6-membered non-aromatic carbocyclyl, substituted or unsubstituted 5- to 6-membered aromatic heterocyclyl, or substituted or unsubstituted 5- to 6-membered non-aromatic heterocyclyl, or pharmaceutically acceptable salt thereof. (e-3) The compound of any one of formula (I) and the above (a) to (d), wherein R.sup.1 is substituted or unsubstituted 6-membered aromatic carbocyclyl, or substituted or unsubstituted 5- to 6-membered aromatic heterocyclyl, or pharmaceutically acceptable salt thereof. (e-4) The compound of any one of formula (I) and the above (a) to (d), wherein R.sup.1 is substituted or unsubstituted phenyl, or substituted or unsubstituted thienyl, or pharmaceutically acceptable salt thereof. (e-5) The compound of any one of formula (I) and the above (a) to (d), wherein R.sup.1 is 6-membered aromatic carbocyclyl substituted with one or more halogen atom(s) and optionally substituted with one or more and same or different substituent(s), 3- to 6-membered non-aromatic carbocyclyl substituted with one or more halogen atom(s) and optionally substituted with one or more and same or different substituent(s), 5- to 6-membered aromatic heterocyclyl substituted with one or more halogen atom(s) and optionally substituted with one or more and same or different substituent(s), or 5- to 6-membered non-aromatic heterocyclyl substituted with one or more halogen atom(s) and optionally substituted with one or more and same or different substituent(s), or pharmaceutically acceptable salt thereof. (e-6) The compound of any one of formula (I) and the above (a) to (d), wherein R.sup.1 is 6-membered aromatic carbocyclyl substituted with one or more halogen atom(s) and optionally substituted with one or more and same or different substituent(s), or 5′ to 6-membered aromatic heterocyclyl substituted with one or more halogen atom(s) and optionally substituted with one or more and same or different substituent(s), or pharmaceutically acceptable salt thereof. (e-7) The compound of any one of formula (I) and the above (a) to (d), wherein R.sup.1 is phenyl substituted with one or more halogen atom(s) and optionally substituted with one or more and same or different substituent(s), or thienyl substituted with one or more halogen atom(s) and optionally substituted with one or more and same or different substituent(s), or pharmaceutically acceptable salt thereof. (e-8) The compound of any one of formula (I) and the above (a) to (d), wherein R.sup.1 is phenyl substituted with one or more halogen atom(s) and optionally substituted with one or more group(s) selected from halogen, alkyl, haloalkyl, alkyloxy, and haloaryloxy, or thienyl substituted with one or more halogen atom(s) and optionally substituted with one or more group(s) selected from halogen, alkyl, haloalkyl, alkyloxy, and haloaryloxy, or pharmaceutically acceptable salt thereof. (e-9) The compound of any one of formula (I) and the above (a) to (d), wherein R.sup.1 is phenyl substituted with one or more halogen atom(s) and optionally substituted with one or more group(s) selected from halogen, alkyl, and haloalkyl, or pharmaceutically acceptable salt thereof. (e-10) The compound of any one of formula (I) and the above (a) to (d), wherein R.sup.1 is a group represented by the formula:

(339) ##STR00047##
wherein Ring E is a 6-membered aromatic carbocycle, a 6-membered non-aromatic carbocycle, a 6-membered aromatic heterocycle, or a 6-membered non-aromatic heterocycle; Ring F is a 5-membered non-aromatic carbocycle, a 5-membered aromatic heterocycle, or a 5-membered non-aromatic heterocycle; R.sup.12a, R.sup.13a, and R.sup.14a are each independently halogen; R.sup.12, R.sup.13, and R.sup.14 are each independently a group selected from the substituent group C; q1 is an integer from 0 to 2; q2 is an integer from 0 to 2; and q3 is 0 or 1,
or pharmaceutically acceptable salt thereof. (e-11) The compound of any one of formula (I) and the above (a) to (d), wherein R.sup.1 is a group represented by the formula:

(340) ##STR00048##
wherein R.sup.12 and R.sup.13 are each independently a group selected from the substituent group C; R.sup.12a and R.sup.13a are each independently halogen; R.sup.12b and R.sup.13b are each independently halogen, alkyl optionally substituted with one or more group(s) selected from the substituent group D, or alkyloxy optionally substituted with one or more group(s) selected from the substituent group D; q1a is 0 or 1; and q2a is 0 or 1,
or pharmaceutically acceptable salt thereof. (e-12) The compound of any one of formula (I) and the above (a) to (d), wherein R.sup.1 is a group represented by the formula:

(341) ##STR00049##
wherein R.sup.12a and R.sup.13a are each independently halogen; and
each of R.sup.12b, R.sup.12e, and R.sup.13b is halogen, alkyl optionally substituted with one or more group(s) selected from the substituent group D, or alkyloxy optionally substituted with one or more group(s) selected from the substituent group D,
or pharmaceutically acceptable salt thereof. (e-13) The compound of any one of the above (e-10) to (e-12), wherein R.sup.12a, R.sup.13a and R.sup.14a are each independently a fluorine atom, or a chlorine atom, or pharmaceutically acceptable salt thereof. (e-14) The compound of any one of the above (e-10) to (e-12), wherein each of R.sup.12a, R.sup.13a and R.sup.14a is a fluorine atom, or pharmaceutically acceptable salt thereof. (e-15) The compound of any one of the above (e-10) to (e-14), wherein R.sup.12b, R.sup.12c and R.sup.13b are each independently halogen, or alkyl optionally substituted with one or more group(s) selected from the substituent group D, or pharmaceutically acceptable salt thereof. (e-16) The compound of any one of the above (e-10) to (e-14), wherein R.sup.12b, R.sup.12c and R.sup.13b are each independently halogen, alkyl, or haloalkyl, or pharmaceutically acceptable salt thereof. (e-17) The compound of any one of the above (e-10) to (e-14), wherein R.sup.12b, R.sup.12c and R.sup.31b are each independently halogen, methyl, or halomethyl, or pharmaceutically acceptable salt thereof. (e-18) The compound of any one of the above (e-10) to (e-14), wherein R.sup.12b, R.sup.12c and R.sup.13b are each independently a fluorine atom, or a chlorine atom, or pharmaceutically acceptable salt thereof. (e-19) The compound of any one of the above (e-10) to (e-14), wherein each of R.sup.12b, R.sup.12c anil R.sup.13b is a fluorine atom, or pharmaceutically acceptable salt thereof. (e-20) The compound of any one of the above (e-10) to (e-19), wherein R.sup.12, R.sup.13, and R.sup.14 are each independently halogen, hydroxy, carboxy, amino, carbamoyl, sulfamoyl, sulfo, cyano, alkyl optionally substituted with one or more group(s) selected from the substituent group D, alkyloxy optionally substituted with one or more group(s) selected from the substituent, group D, alkylamino optionally substituted with one or more group(s) selected from the substituent group D, or alkylsulfanyl optionally substituted with one or more group(s) selected from the substituent, group D, or pharmaceutically acceptable salt thereof. (e-21) The compound of any one of the above (e-10) to (e-19), wherein R.sup.12, R.sup.13, and R.sup.14 are each independently halogen, cyano, alkyl optionally substituted with one or more group(s) selected from the substituent group D, or alkyloxy optionally substituted with one or more group(s) selected from the substituent group D, or pharmaceutically acceptable salt thereof. (e-22) The compound of any one of the above (e-10) to (e-19), wherein R.sup.12, R.sup.13, and R.sup.14 are each independently halogen, alkyl, or haloalkyl, or pharmaceutically acceptable salt thereof. (e-23) The compound of any one of the above (e-10) to (e-19), wherein R.sup.12, R.sup.13, and R.sup.14 are each independently halogen, methyl, or halomethyl, or pharmaceutically acceptable salt thereof. (e-24) The compound of any one of the above (e-10) to (e-19), wherein R.sup.12, R.sup.13, and R.sup.14 are each independently a fluorine atom, or a chlorine atom, or pharmaceutically acceptable salt thereof. (e-25) The compound of any one of the above (e-10) to (e-19), wherein each of R.sup.12, R.sup.13, and R.sup.14 is a fluorine atom, or pharmaceutically acceptable salt thereof. (e-26) The compound of any one of the above (e-10) to (e-25), wherein each of q1, q2, and q3 is 0, or pharmaceutically acceptable salt thereof. (e-27) The compound of any one of the above (e-10) to (e-25), wherein each of q1, q2, and q3 is 1, or pharmaceutically acceptable salt thereof. (e-28) The compound of any one of the above (e-10) to (e-25), wherein each of q1 and q2 is 2, or pharmaceutically acceptable salt, thereof. (e-29) The compound of any one of the above (e-10) to (e-25), wherein each of q1a and q2a is 0, or pharmaceutically acceptable salt thereof. (e-30) The compound of any one of the above (e-10) to (e-25), wherein each of q1a and q2a is 1, or pharmaceutically acceptable salt thereof. (e-31) The compound of any one of the above (e-10) to (e-30), wherein Ring E is cyclohexene, benzene or a 0-membered aromatic heterocycle, or pharmaceutically acceptable salt thereof. (e-32) The compound of any one of the above (e-10) to (e-30), wherein Ring E is benzene, or a 6-membered aromatic heterocycle, or pharmaceutically acceptable salt thereof. (e-33) The compound of any one of the above (e-10) to (e-30), wherein Ring E is benzene, pyridine, pyrimidine, or pyrazine, or pharmaceutically acceptable salt thereof. (e-31) The compound of any one of the above (e-10) to (e-30), wherein Ring E is benzene, or pyridine, or pharmaceutically acceptable salt thereof. (e-35) The compound of any one of the above (e-10) to (e-30), wherein Ring E is benzene, or pharmaceutically acceptable salt thereof. (e-36) The compound of any one of the above (e-10) to (e-35), wherein Ring F is a 5-membered aromatic heterocycle, or pharmaceutically acceptable salt thereof. (e-37) The compound of any one of the above (e-10) to (e-35), wherein Ring F is thiophene, or pharmaceutically acceptable salt thereof. (f) A compound according to any one of the following (f-1) to (f-21) or a pharmaceutically acceptable salt thereof. (f-1) The compound of any one of formula (I) and the above (a) to (e), wherein R.sup.8 is a group represented by the Formula:

(342) ##STR00050##
wherein

(343) R.sup.9a and R.sup.9b are each independently halogen, hydroxy, carboxy, amino, carbamoyl, sulfamoyl, sulfo, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkenyloxy, substituted or unsubstituted alkynyloxy, substituted or unsubstituted alkylsulfanyl, substituted or unsubstituted alkenylsulfanyl, substituted or unsubstituted alkynylsulfanyl, substituted or unsubstituted alkylamino, substituted or unsubstituted alkenylamino, substituted or unsubstituted alkynylamino, substituted or unsubstituted alkylcarbonyl, substituted or unsubstituted alkenylcarbonyl, substituted or unsubstituted alkynylcarbonyl, substituted or unsubstituted alkylsulfonyl, substituted or unsubstituted alkenylsulfonyl, substituted or unsubstituted alkynylsulfonyl, substituted or unsubstituted alkylcarbonyloxy, substituted or unsubstituted alkenylcarbonyloxy, substituted or unsubstituted alkynylcarbonyloxy, substituted or unsubstituted alkyloxycarbonyl, substituted or unsubstituted alkenyloxycarbonyl, substituted or unsubstituted alkynyloxycarbonyl, substituted or unsubstituted alkylsulfonyloxy, substituted or unsubstituted alkenylsulfonyloxy, substituted or unsubstituted alkynylsulfonyloxy, substituted or unsubstituted aryloxysulfonyl, substituted or unsubstituted alkenyloxysulfonyl, substituted or unsubstituted alkynyloxysulfonyl, substituted or unsubstituted alkylcarbamoyl, substituted or unsubstituted alkenylcarbamoyl, substituted or unsubstituted alkynylcarbamoyl, substituted or unsubstituted alkylsulfamoyl, substituted or unsubstituted alkenylsulfamoyl, substituted or unsubstituted alkynylsulfamoyl, substituted or unsubstituted alkylcarbonylamino, substituted or unsubstituted alkenylcarbonylamino, substituted or unsubstituted alkynylcarbonylamino, substituted or unsubstituted alkylsulfonylamino, substituted or unsubstituted alkenylsulfonylamino, substituted or unsubstituted aromatic carbocyclyl, substituted or unsubstituted non-aromatic carbocyclyl, substituted or unsubstituted aromatic heterocyclyl, substituted or unsubstituted non-aromatic heterocyclyl, substituted or unsubstituted aromatic carbocyclyloxy, substituted or unsubstituted non-aromatic carbocyclyloxy, substituted or unsubstituted aromatic heterocyclyloxy, substituted or unsubstituted non-aromatic heterocyclyloxy, substituted or unsubstituted aromatic carbocyclylamino, substituted or unsubstituted non-aromatic carbocyclylamino, substituted or unsubstituted aromatic heterocyclylamino, substituted or unsubstituted non-aromatic heterocyclylamino, substituted or unsubstituted aromatic carbocyclylsulfanyl, substituted or unsubstituted non-aromatic carbocyclylsulfanyl, substituted or unsubstituted aromatic heterocyclylsulfanyl, substituted or unsubstituted non-aromatic heterocyclylsulfanyl, substituted or unsubstituted aromatic carbocyclylcarbonyl, substituted or unsubstituted non-aromatic carbocyclylcarbonyl, substituted or unsubstituted aromatic heterocyclylcarbonyl, substituted or unsubstituted non-aromatic heterocyclylcarbonyl, substituted or unsubstituted aromatic carbocyclylsulfonyl, substituted or unsubstituted non-aromatic carbocyclylsulfonyl, substituted or unsubstituted aromatic heterocyclylsulfonyl, substituted or unsubstituted non-aromatic heterocyclylsulfonyl, substituted or unsubstituted aromatic carbocyclylcarbonyloxy, substituted or unsubstituted non-aromatic carbocyclylcarbonyloxy, substituted or unsubstituted aromatic heterocyclylcarbonyloxy, substituted or unsubstituted non-aromatic heterocyclylcarbonyloxy, substituted or unsubstituted aromatic carbocyclyloxycarbonyl, substituted or unsubstituted non-aromatic carbocyclyloxycarbonyl, substituted or unsubstituted aromatic heterocyclyloxycarbonyl, substituted or unsubstituted non-aromatic heterocyclyloxycarbonyl, substituted or unsubstituted aromatic carbocyclylsulfonyloxy, substituted or unsubstituted non-aromatic carbocyclylsulfonyloxy, substituted or unsubstituted aromatic heterocyclylsulfonyloxy, substituted or unsubstituted non-aromatic heterocyclylsulfonyloxy, substituted or unsubstituted aromatic carbocyclyloxysulfonyl, substituted or unsubstituted non-aromatic carbocyclyloxysulfonyl, substituted or unsubstituted aromatic heterocyclyloxysulfonyl, substituted or unsubstituted non-aromatic heterocyclyloxysulfonyl, substituted or unsubstituted aromatic carbocyclylcarbamoyl, substituted or unsubstituted non-aromatic carbocyclylcarbamoyl, substituted or unsubstituted aromatic heterocyclylcarbamoyl, substituted or unsubstituted non-aromatic heterocyclylcarbamoyl, substituted or unsubstituted aromatic carbocyclylsulfamoyl, substituted or unsubstituted non-aromatic carbocyclylsulfamoyl, substituted or unsubstituted aromatic heterocyclylsulfamoyl, substituted or unsubstituted non-aromatic heterocyclylsulfamoyl, substituted or unsubstituted aromatic carbocyclylcarbonylamino, substituted or unsubstituted non-aromatic carbocyclylcarbonylamino, substituted or unsubstituted aromatic heterocyclylcarbonyl amino, substituted or unsubstituted non-aromatic heterocyclylcarbonylamino, substituted or unsubstituted aromatic carbocyclylsulfonylamino, substituted or unsubstituted non-aromatic carbocyclylsulfonylamino, substituted or unsubstituted aromatic heterocyclylsulfonylamino, substituted or unsubstituted non-aromatic heterocyclylsulfonylamino, substituted or unsubstituted aromatic carbocyclyloxycarbonylamino, substituted or unsubstituted non-aromatic carbocyclyloxycarbonylamino, substituted or unsubstituted aromatic heterocyclyloxycarbonylamino, or substituted or unsubstituted non-aromatic heterocyclyloxy carbonylamino:

(344) R.sup.10a and R.sup.10b are each independently halogen, hydroxy, carboxy, amino, carbamoyl, sulfamoyl, sulfo, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkenyloxy, substituted or unsubstituted alkynyloxy, substituted or unsubstituted alkylsulfanyl, substituted or unsubstituted alkenylsulfinyl, substituted or unsubstituted alkynylsulfanyl, substituted or unsubstituted alkylamino, substituted or unsubstituted alkenylamino, substituted or unsubstituted alkynylamino, substituted or unsubstituted alkylcarbonyl, substituted or unsubstituted alkenylcarbonyl, substituted or unsubstituted alkynylcarbonyl, substituted or unsubstituted alkylsulfonyl, substituted or unsubstituted alkenylsulfonyl, substituted or unsubstituted alkynylsulfonyl, substituted or unsubstituted alkylcarbonyloxy, substituted or unsubstituted alkenylcarbonyloxy, substituted or unsubstituted alkynylcarbonyloxy, substituted or unsubstituted alkyloxycarbonyl, substituted or unsubstituted alkenyloxycarbonyl, substituted or unsubstituted alkynyloxycarbonyl, substituted or unsubstituted alkylsulfonyloxy, substituted or unsubstituted alkenylsulfonyloxy, substituted or unsubstituted alkynylsulfonyloxy, substituted or unsubstituted aryloxysulfonyl, substituted or unsubstituted alkenyloxysulfonyl, substituted or unsubstituted alkynyloxysulfonyl, substituted or unsubstituted alkylcarbamoyl, substituted or unsubstituted alkenylcarbamoyl, substituted or unsubstituted alkynylcarbamoyl, substituted or unsubstituted alkylsulfamoyl, substituted or unsubstituted alkenylsulfamoyl, substituted or unsubstituted alkynylsulfamoyl, substituted or unsubstituted alkylcarbonylamino, substituted or unsubstituted alkenylcarbonylamino, substituted or unsubstituted alkynylcarbonylamino, substituted or unsubstituted alkylsulfonylamino, substituted or unsubstituted alkenylsulfonylamino, substituted or unsubstituted alkynylsulfonylamino, substituted or unsubstituted aromatic carbocyclyl, substituted or unsubstituted non-aromatic carbocyclyl, substituted or unsubstituted aromatic heterocyclyl, substituted or unsubstituted non-aromatic heterocyclyl, substituted or unsubstituted aromatic carbocyclyloxy, substituted or unsubstituted non-aromatic carbocyclyloxy, substituted or unsubstituted aromatic heterocyclyloxy, substituted or unsubstituted non-aromatic heterocyclyloxy, substituted or unsubstituted aromatic carbocyclyl amino, substituted or unsubstituted non-aromatic carbocyclylmino, substituted or unsubstituted aromatic heterocyclylamino, substituted or unsubstituted non-aromatic heterocyclylamino, substituted or unsubstituted aromatic carbocyclyl sulfanyl, substituted or unsubstituted non-aromatic carbocyclylsulfanyl, substituted or unsubstituted aromatic heterocyclylsulfanyl, substituted or unsubstituted non-aromatic heterocyclylsulfanyl, substituted or unsubstituted aromatic carbocyclylcarbonyl, substituted or unsubstituted non-aromatic carbocyclylcarbonyl, substituted or unsubstituted aromatic heterocyclylcarbonyl, substituted or unsubstituted non-aromatic heterocyclylcarbonyl, substituted or unsubstituted aromatic carbocyclylsulfonyl, substituted or unsubstituted non-aromatic carbocyclyl sulfonyl, substituted or unsubstituted aromatic heterocyclyl sulfonyl, substituted or unsubstituted non-aromatic heterocyclylsulfonyl, substituted or unsubstituted aromatic carbocyclylcarbonyloxy, substituted or unsubstituted non-aromatic carbocyclylcarbonyloxy, substituted or unsubstituted aromatic heterocyclylcarbonyloxy, substituted or unsubstituted non-aromatic heterocyclylcarbonyloxy, substituted or unsubstituted aromatic carbocyclyloxycarbonyl, substituted or unsubstituted non-aromatic carbocyclyloxycarbonyl, substituted or unsubstituted aromatic heterocyclyloxycarbonyl, substituted or unsubstituted non-aromatic heterocyclyloxycarbonyl, substituted or unsubstituted aromatic carbocyclylsulfonyloxy, substituted or unsubstituted non-aromatic carbocyclylsulfonyloxy, substituted or unsubstituted aromatic heterocyclylsulfonyloxy, substituted or unsubstituted non-aromatic heterocyclylsulfonyloxy, substituted or unsubstituted aromatic carbocyclyloxysulfonyl, substituted or unsubstituted non-aromatic carbocyclyloxysulfonyl, substituted or unsubstituted aromatic heterocyclyloxysulfonyl, substituted or unsubstituted non-aromatic heterocyclyloxysulfonyl, substituted or unsubstituted aromatic carbocyclylcarbamoyl, substituted or unsubstituted non-aromatic carbocyclylcarbamoyl, substituted or unsubstituted aromatic heterocyclylcarbamoyl, substituted or unsubstituted non-aromatic heterocyclylcarbamoyl, substituted or unsubstituted aromatic carbocyclylsulfamoyl, substituted or unsubstituted non-aromatic carbocyclylsulfamoyl, substituted or unsubstituted aromatic heterocyclylsulfamoyl, substituted or unsubstituted non-aromatic heterocyclylsulfamoyl, substituted or unsubstituted aromatic carbocyclylcarbonylamino, substituted or unsubstituted non-aromatic carbocyclylcarbonyl amino, substituted or unsubstituted aromatic heterocyclylcarbonyl amino, substituted or unsubstituted non-aromatic heterocyclylcarbonylamino, substituted or unsubstituted aromatic carbocyclylsulfonylamino, substituted or unsubstituted non-aromatic carbocyclylsulfonylamino, substituted or unsubstituted aromatic heterocyclylsulfonylamino, substituted or unsubstituted non-aromatic heterocyclylsulfonylamino, substituted or unsubstituted aromatic carbocyclyloxycarbonylamino, substituted or unsubstituted non-aromatic carbocyclyloxycarbonylamino, substituted or unsubstituted aromatic heterocyclyloxycarbonylamino, or substituted or unsubstituted non-aromatic heterocyclyloxycarbonylamino: p1 is an integer from 0 to 3; and p2 is an integer from 0 to 2,
or pharmaceutically acceptable salt thereof. (f-2) The compound of the above (f-1), wherein R.sup.3 is

(345) ##STR00051##
or pharmaceutically acceptable salt thereof. (f-3) The compound of the above (f-1), wherein R.sup.3 is

(346) ##STR00052##
or pharmaceutically acceptable salt thereof. (f-4) The compound of any one of the above (f-1) to (f-3), wherein R.sup.10a and R.sup.10b are each independently halogen, hydroxy, amino, carbamoyl, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkenyloxy, substituted or unsubstituted alkynyloxy, substituted or unsubstituted alkylsulfanyl, substituted or unsubstituted alkenylsulfanyl, substituted or unsubstituted alkynylsulfanyl, substituted or unsubstituted alkylamino, substituted or unsubstituted alkenylamino, substituted or unsubstituted alkynylamino, substituted or unsubstituted alkylcarbonyl, substituted or unsubstituted alkenylcarbonyl, substituted or unsubstituted alkynylcarbonyl, substituted or unsubstituted alkylsulfonyl, substituted or unsubstituted alkenylsulfonyl, substituted or unsubstituted alkynyl sulfonyl, substituted or unsubstituted alkyloxycarbonyl, substituted or unsubstituted alkenyloxycarbonyl, substituted or unsubstituted alkynyloxycarbonyl, substituted or unsubstituted aryloxysulfonyl, substituted or unsubstituted alkenyloxysulfonyl, substituted or unsubstituted alkynyloxysulfonyl, substituted or unsubstituted aromatic carbocyclyl, substituted or unsubstituted non-aromatic carbocyclyl, substituted or unsubstituted aromatic heterocyclyl, substituted or unsubstituted non-aromatic heterocyclyl, substituted or unsubstituted aromatic carbocyclyloxy, substituted or unsubstituted non-aromatic carbocyclyloxy, substituted or unsubstituted aromatic heterocyclyloxy, substituted or unsubstituted non-aromatic heterocyclyloxy, substituted or unsubstituted aromatic carbocyclylamino, substituted or unsubstituted non-aromatic carbocyclylamino, substituted or unsubstituted aromatic heterocyclylamino, substituted or unsubstituted non-aromatic heterocyclylamino, substituted or unsubstituted aromatic carbocyclylsulfanyl, substituted or unsubstituted non-aromatic carbocyclylsulfanyl, substituted or unsubstituted aromatic heterocyclylsulfanyl, or substituted or unsubstituted non-aromatic heterocyclylsulfanyl, or pharmaceutically acceptable salt thereof. (f-5) The compound of any one of the above (f-1) to (f-3), wherein R.sup.10a and R.sup.10b are each independently halogen, hydroxy, amino, carbamoyl, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkylsulfanyl, substituted or unsubstituted alkylamino, substituted or unsubstituted alkylcarbonyl, substituted or unsubstituted alkylsulfonyl, substituted or unsubstituted alkyloxycarbonyl, substituted or unsubstituted aryloxysulfonyl, substituted or unsubstituted aromatic carbocyclyl, substituted or unsubstituted non-aromatic carbocyclyl, substituted or unsubstituted aromatic heterocyclyl, substituted or unsubstituted non-aromatic heterocyclyl, substituted or unsubstituted aromatic carbocyclyloxy, substituted or unsubstituted non-aromatic carbocyclyloxy, substituted or unsubstituted aromatic heterocyclyloxy, substituted or unsubstituted non-aromatic heterocyclyloxy, substituted or unsubstituted aromatic carbocyclylamino, substituted or unsubstituted non-aromatic carbocyclylamino, substituted or unsubstituted aromatic heterocyclylamino, substituted or unsubstituted non-aromatic heterocyclylamino, substituted or unsubstituted aromatic, carbocyclylsulfanyl, substituted or unsubstituted non-aromatic carbocyclylsulfanyl, substituted or unsubstituted aromatic heterocyclylsulfanyl, or substituted or unsubstituted non-aromatic heterocyclylsulfanyl, or pharmaceutically acceptable salt thereof. (f-6) The compound of any one of the above (f-1) to (f-3), wherein R.sup.10a and R.sup.10b are each independently halogen, hydroxy, amino, carbamoyl, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkylsulfanyl, substituted or unsubstituted alkylamino, substituted or unsubstituted alkylcarbonyl, substituted or unsubstituted alkylsulfonyl, substituted or unsubstituted alkyloxycarbonyl, substituted or unsubstituted aryloxysulfonyl, substituted or unsubstituted aromatic carbocyclyl, substituted or unsubstituted non-aromatic carbocyclyl, substituted or unsubstituted aromatic heterocyclyl, substituted or unsubstituted non-aromatic heterocyclyl, substituted or unsubstituted aromatic carbocyclyloxy, substituted or unsubstituted non-aromatic carbocyclyloxy, substituted or unsubstituted aromatic heterocyclyloxy, or substituted or unsubstituted non-aromatic heterocyclyloxy, or pharmaceutically acceptable salt thereof. (f-7) The compound of any one of the above (f-1) to (f-3), wherein R.sup.10a and R.sup.10b are each independently halogen, hydroxy, carbamoyl, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkylsulfanyl, substituted or unsubstituted alkylamino, substituted or unsubstituted alkylcarbonyl, substituted or unsubstituted alkylsulfonyl, substituted or unsubstituted alkyloxycarbonyl, substituted or unsubstituted aromatic heterocyclyl, substituted or unsubstituted non-aromatic heterocyclyl, substituted or unsubstituted aromatic carbocyclyloxy, or substituted or unsubstituted aromatic heterocyclyloxy, or pharmaceutically acceptable salt thereof. (f-8) The compound of any one of the above (f-1) to (f-3), wherein R.sup.10a and R.sup.10b are each independently halogen; hydroxy; carbamoyl; cyano; alkyl substituted with one or more group(s) selected from halogen, hydroxy, alkyloxy, and a non-aromatic heterocycle; unsubstituted alkyl; alkenyl substituted with one or more group(s) selected from halogen, hydroxy, alkyloxy, and a non-aromatic heterocycle; unsubstituted alkenyl; alkynyl substituted with one or more group(s) selected from halogen, hydroxy, alkyloxy, and a non-aromatic heterocycle; unsubstituted alkynyl; alkyloxy substituted with one or more group(s) selected from halogen, hydroxy, alkyloxy, and a non-aromatic heterocycle; unsubstituted alkyloxy; alkylsulfanyl substituted with one or more group(s) selected from halogen, hydroxy, alkyloxy, and a non-aromatic heterocycle; unsubstituted alkylsulfanyl; alkylamino substituted with one or more group(s) selected from halogen, hydroxy, alkyloxy, and a non-aromatic heterocyclo; unsubstituted alkylamino; alkylcarbonyl substituted with one or more group(s) selected from halogen, hydroxy, alkyloxy, and a non-aromatic heterocycle; unsubstituted alkylcarbonyl; alkylsulfonyl substituted with one or more group(s) selected from halogen, hydroxy, alkyloxy, and a non-aromatic heterocycle; unsubstituted alkylsulfonyl; alkyloxycarbonyl substituted with one or more group(s) selected from halogen, hydroxy, alkyloxy, and a non-aromatic heterocycle; unsubstituted alkyloxycarbonyl; aromatic heterocyclyl substituted with one or more group(s) selected from halogen, alkyl, alkyloxy, and alkyloxycarbonyl; unsubstituted aromatic heterocyclyl; non-aromatic heterocyclyl substituted with one or more group(s) selected from halogen, alkyl, alkyloxy, and alkyloxycarbonyl; unsubstituted non-aromatic heterocyclyl; aromatic carbocyclyloxy substituted with one or more group(s) selected from halogen, alkyl, alkyloxy, and alkyloxycarbonyl; unsubstituted aromatic carbocyclyloxy; aromatic heterocyclyloxy substituted with one or more group(s) selected from halogen, alkyl, alkyloxy, and alkyloxycarbonyl; or unsubstituted aromatic heterocyclyloxy,
or pharmaceutically acceptable salt thereof. (f-9) The compound of any one of the above (f-1) to (f-3), wherein R.sup.10a and R.sup.10b are each independently halogen; hydroxy; carbamoyl; cyano; alkyl substituted with one or more group(s) selected from halogen, hydroxy, alkyloxy, and a non-aromatic heterocycle; unsubstituted alkyl; unsubstituted alkenyl; unsubstituted alkynyl; alkyloxy substituted with one or more group(s) selected from halogen; unsubstituted alkyloxy; alkylsulfanyl substituted with one or more group(s) selected from halogen; unsubstituted alkylsulfanyl; unsubstituted alkylamino; unsubstituted alkylcarbonyl; unsubstituted alkylsulfonyl; unsubstituted alkyloxycarbonyl; aromatic heterocyclyl substituted with one or more group(s) selected from alkyl and alkyloxy; unsubstituted aromatic heterocyclyl; non-aromatic heterocyclyl substituted with one or more group(s) selected from alkyl and alkyloxycarbonyl; unsubstituted non-aromatic heterocyclyl; unsubstituted aromatic carbocyclyloxy; aromatic heterocyclyloxy substituted with one or more group(s) selected from halogen; or unsubstituted aromatic heterocyclyloxy, or pharmaceutically acceptable salt thereof. (f10) The compound of any one of the above (f-1) to (f-3), wherein R.sup.10a and R.sup.10b are each independently halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkenyloxy, substituted or unsubstituted alkynyloxy, substituted or unsubstituted aromatic carbocyclyl, substituted or unsubstituted non-aromatic carbocyclyl, substituted or unsubstituted aromatic heterocyclyl, substituted or unsubstituted non-aromatic heterocyclyl, substituted or unsubstituted aromatic carbocyclyloxy, substituted or unsubstituted non-aromatic carbocyclyloxy, substituted or unsubstituted aromatic heterocyclyloxy, or substituted or unsubstituted non-aromatic heterocyclyloxy, or pharmaceutically acceptable salt thereof. (f-11) The compound of any one of the above (f-1) to (f-3), wherein R.sup.10a and R.sup.10b are each independently halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkylsulfanyl, substituted or unsubstituted alkylamino, substituted or unsubstituted alkylcarbonyl, substituted or unsubstituted alkylsulfonyl, substituted or unsubstituted aromatic carbocyclyl, substituted or unsubstituted non-aromatic carbocyclyl, substituted or unsubstituted aromatic heterocyclyl, substituted or unsubstituted non-aromatic heterocyclyl, substituted or unsubstituted aromatic carbocyclyloxy, substituted or unsubstituted non-aromatic carbocyclyloxy, substituted or unsubstituted aromatic heterocyclyloxy, substituted or unsubstituted non-aromatic heterocyclyloxy, substituted or unsubstituted aromatic carbocyclylamino, substituted or unsubstituted non-aromatic carbocyclylamino, substituted or unsubstituted aromatic heterocyclylamino, substituted or unsubstituted non-aromatic heterocyclylamino, substituted or unsubstituted aromatic carbocyclylsulfanyl, substituted or unsubstituted non-aromatic carbocyclylsulfanyl, substituted or unsubstituted aromatic heterocyclylsulfanyl, or substituted or unsubstituted non-aromatic heterocyclyl sulfanyl, or pharmaceutically acceptable salt thereof. (f-12) The compound of any one of the above (f-1) to (f-3), wherein R.sup.10a and R.sup.10b are each independently halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted aromatic carbocyclyl, substituted or unsubstituted non-aromatic carbocyclyl, substituted or unsubstituted aromatic heterocyclyl, substituted or unsubstituted noil-aromatic heterocyclyl, substituted or unsubstituted aromatic carboey cl yloxy, substituted or unsubstituted non-aromatic carbocyclyloxy, substituted or unsubstituted aromatic heterocyclyloxy, or substituted or unsubstituted non-aromatic heterocyclyloxy, or pharmaceutically acceptable salt thereof. (f-13) The compound of any one of the above (f-1) to (f-3), wherein R.sup.10a and R.sup.0b are each independently halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkylsulfanyl, substituted or unsubstituted alkylamino, substituted or unsubstituted aromatic heterocyclyl, substituted or unsubstituted non-aromatic heterocyclyl, substituted or unsubstituted aromatic heterocyclyloxy, substituted or unsubstituted non-aromatic heterocyclyloxy, substituted or unsubstituted aromatic heterocyclylamino, substituted or unsubstituted non-aromatic heterocyclylamino, substituted or unsubstituted aromatic heterocyclylsulfanyl, or substituted or unsubstituted non-aromatic heterocyclylsulfanyl, or pharmaceutically acceptable salt thereof. (f-14) The compound of any one of the above (f-1) to (f-3), wherein R.sup.10a and R.sup.10b are each independently halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted aromatic heterocyclyl, substituted or unsubstituted non-aromatic heterocyclyl, substituted or unsubstituted aromatic heterocyclyloxy, or substituted or unsubstituted non-aromatic heterocyclyloxy, or pharmaceutically acceptable salt thereof. (f-15) The compound of any one of the above (f-1) to (f-3), wherein R.sup.10a and R.sup.10b are each independently halogen; alkyl; haloalkyl; alkyloxy; haloalkyloxy; aromatic heterocyclyl substituted with one or more group(s) selected from halogen, alkyl, haloalkyl, alkyloxy, and haloalkyloxy; unsubstituted aromatic heterocyclyl; non-aromatic heterocyclyl substituted with one or more group(s) selected from halogen, alkyl, haloalkyl, alkyloxy, and haloalkyloxy; unsubstituted non-aromatic heterocyclyl; aromatic heterocyclyloxy substituted with one or more group(s) selected from halogen, alkyl, haloalkyl, alkyloxy, and haloalkyloxy; or unsubstituted aromatic heterocyclyloxy, or pharmaceutically acceptable salt thereof. (f-16) The compound of any one of the above (f-1) to (f-1.5), wherein p1 is 1 or 2, or pharmaceutically acceptable salt thereof. (f-17) The compound of any one of the above (f-1) to (f-15), wherein p1 is 2, or pharmaceutically acceptable salt thereof. (f-18) The compound of any one of the above (f-1) to (f-15), wherein p1 is 1, or pharmaceutically acceptable salt thereof. (f-19) The compound of any one of the above (f-1) to (f-1.5), wherein p1 is 0, or pharmaceutically acceptable salt thereof. (f-20) The compound of any one of the above (f-1) to (f-9), wherein p2 is 1, or pharmaceutically acceptable salt thereof. (f-21) The compound of any one of the above (f-1) to (f-19), wherein p2 is 0, or pharmaceutically acceptable salt thereof. (g) A compound according to any one of the following (g-1) to (g-51) or a pharmaceutically acceptable salt thereof. (g-1) The compound of any one of Formula (I) and the above (a) to (f), wherein R.sup.3 is a group represented by the Formula:

(347) ##STR00053##
wherein R.sup.10aa, R.sup.10ab, and R.sup.10ac are each independently the same as R.sup.10a of the above (f-1),
or pharmaceutically acceptable salt thereof. (g-2) The compound of any one of Formula (I) and the above (a) to (f), wherein R.sup.3 is

(348) ##STR00054##
or pharmaceutically acceptable salt thereof. (g-3) The compound of any one of Formula (I) and the above (a) to (f), wherein R.sup.3 is

(349) ##STR00055##
or pharmaceutically acceptable salt thereof. (g-4) The compound of any one of Formula (I) and the above (a) to (f), wherein R.sup.3 is

(350) ##STR00056##
or pharmaceutically acceptable salt thereof. (g-5) The compound of any one of Formula (I) and the above (a) to (f), wherein R.sup.3 is

(351) ##STR00057##
or pharmaceutically acceptable salt thereof. (g-6) The compound of any one of Formula (I) and the above (a) to (f), wherein R.sup.3 is

(352) ##STR00058##
or pharmaceutically acceptable salt thereof. (g-7) The compound of any one of Formula (I) and the above (a) to (f), wherein R.sup.3 is

(353) ##STR00059##
or pharmaceutically acceptable salt thereof. (g-8) The compound of any one of Formula (I) and the above (a) to (f), wherein R.sup.3 is

(354) ##STR00060##
or pharmaceutically acceptable salt thereof. (g-9) The compound of any one of Formula (I) and the above (a) to (f), wherein R.sup.3 is

(355) ##STR00061##
or pharmaceutically acceptable salt thereof. (g-10) The compound of any one of the above (g-1) to (g-9), wherein R.sup.10aa is halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkenyloxy, substituted or unsubstituted alkynyloxy, substituted or unsubstituted alkylsulfanyl, substituted or unsubstituted alkenylsulfonyl, substituted or unsubstituted alkynylsulfanyl, substituted or unsubstituted alkylamino, substituted or unsubstituted alkenylamino, substituted or unsubstituted alkynylamino, substituted or unsubstituted alkyloxycarbonyl, substituted or unsubstituted alkenyloxycarbonyl, substituted or unsubstituted alkynyloxycarbonyl, substituted or unsubstituted aromatic carbocyclyl, substituted or unsubstituted non-aromatic carbocyclyl, substituted or unsubstituted aromatic heterocyclyl, substituted or unsubstituted non-aromatic heterocyclyl, substituted or unsubstituted aromatic carbocyclyloxy, substituted or unsubstituted non-aromatic carbocyclyloxy, substituted or unsubstituted aromatic heterocyclyloxy, or substituted or unsubstituted non-aromatic heterocyclyloxy, or pharmaceutically acceptable salt thereof. (g-11) The compound of any one of the above (g-1) to (g-9), wherein R.sup.10aa is halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkylsulfanyl, substituted or unsubstituted alkylamino, substituted or unsubstituted alkyloxycarbonyl, substituted or unsubstituted aromatic carbocyclyl, substituted or unsubstituted non-aromatic carbocyclyl, substituted or unsubstituted aromatic heterocyclyl, substituted or unsubstituted non-aromatic heterocyclyl, substituted or unsubstituted aromatic carbocyclyloxy, substituted or unsubstituted non-aromatic carbocyclyloxy, substituted or unsubstituted aromatic heterocyclyloxy, or substituted or unsubstituted non-aromatic heterocyclyloxy, or pharmaceutically acceptable salt thereof. (g-12) The compound of any one of the above (g-1) to (g-9), wherein R.sup.10aa is halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkylsulfanyl, substituted or unsubstituted alkylamino, substituted or unsubstituted alkyloxycarbonyl, substituted or unsubstituted aromatic heterocyclyl, or substituted or unsubstituted aromatic carbocyclyloxy, or pharmaceutically acceptable salt thereof. (g-13) The compound of any one of the above (g-1) to (g-9), wherein R.sup.10aa is halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkenyloxy, substituted or unsubstituted alkynyloxy, substituted or unsubstituted alkylsulfanyl, substituted or unsubstituted alkenylsulfanyl, substituted or unsubstituted alkynylsulfanyl, substituted or unsubstituted alkylamino, substituted or unsubstituted alkenylamino, or substituted or unsubstituted alkynylamino, or pharmaceutically acceptable salt thereof. (g-14) The compound of any one of the above (g-1) to (g-9), wherein R.sup.10aa is halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkylsulfanyl, or substituted or unsubstituted alkylamino, or pharmaceutically acceptable salt thereof. (g-15) The compound of any one of the above (g-1) to (g-9), wherein R.sup.10aa is halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy, or pharmaceutically acceptable salt thereof. (g-16) The compound of any one of the above (g-1) to (g-9), wherein R.sup.10aa is halogen, alkyl, haloalkyl, alkyloxy, or haloalkyloxy, or pharmaceutically acceptable salt thereof. (g-17) The compound of any one of the above (g-1) to (g-9), wherein R.sup.10aa is alkyl substituted with one or more group (s) selected from halogen, hydroxy, and alkyloxy; unsubstituted alkyl; alkyloxy substituted with one or more group(s) selected from halogen, hydroxy, and alkyloxy; unsubstituted alkyloxy; alkylamino substituted with one or more group(s) selected from halogen, hydroxy, and alkyloxy; unsubstituted alkylamino; alkylsulfanyl substituted with one or more group(s) selected from halogen, hydroxy, and alkyloxy; unsubstituted alkylsulfanyl; alkyloxycarbonyl substituted with one or more group(s) selected from halogen, hydroxy, and alkyloxy; unsubstituted alkyloxycarbonyl; unsubstituted aromatic heterocyclyl; or unsubstituted aromatic carbocyclyloxy, or pharmaceutically acceptable salt thereof. (g-18) The compound of any one of the above (g-1) to (g-9), wherein R.sup.10aa is alkyl substituted with one or more group(s) selected from halogen, hydroxy, and alkyloxy; unsubstituted alkyl; alkyloxy substituted with one or more group(s) selected from halogen; unsubstituted alkyloxy: unsubstituted alkylamino; unsubstituted alkylsulfanyl; unsubstituted alkyloxycarbonyl; unsubstituted aromatic heterocyclyl; or unsubstituted aromatic carbocyclyloxy,
or pharmaceutically acceptable salt thereof. (g-19) The compound of any one of the above (g-1) to (g-9), wherein R.sup.10aa is halogen, or pharmaceutically acceptable salt thereof. (g-20) The compound of any one of the above (g-1) to (g-19), wherein R.sup.10ab is halogen, hydroxy, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkenyloxy, substituted or unsubstituted alkynyloxy, substituted or unsubstituted alkylsulfanyl, substituted or unsubstituted alkenylsulfanyl, substituted or unsubstituted alkynylsulfanyl, substituted or unsubstituted alkylamino, substituted or unsubstituted alkenylamino, substituted or unsubstituted alkynylamino, substituted or unsubstituted aromatic carbocyclyl, substituted or unsubstituted non-aromatic carbocyclyl, substituted or unsubstituted aromatic heterocyclyl, substituted or unsubstituted non-aromatic heterocyclyl, substituted or unsubstituted aromatic carbocyclyloxy, substituted or unsubstituted non-aromatic carbocyclyloxy, substituted or unsubstituted aromatic heterocyclyloxy, or substituted or unsubstituted non-aromatic heterocyclyloxy, or pharmaceutically acceptable salt, thereof. (g-21) The compound of any one of the above (g-1) to (g-19), wherein R.sup.10ab is halogen, hydroxy, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkylsulfanyl, substituted or unsubstituted alkylamino, substituted or unsubstituted aromatic carbocyclyl, substituted or unsubstituted non-aromatic carbocyclyl, substituted or unsubstituted aromatic heterocyclyl, substituted or unsubstituted non-aromatic heterocyclyl, substituted or unsubstituted aromatic carbocyclyloxy, substituted or unsubstituted non-aromatic carbocyclyloxy, substituted or unsubstituted aromatic heterocyclyloxy, or substituted or unsubstituted non-aromatic heterocyclyloxy, or pharmaceutically acceptable salt thereof. (g-22) The compound of any one of the above (g-1) to (g-19), wherein R.sup.10ab is halogen, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted non-aromatic heterocyclyl, or substituted or unsubstituted aromatic heterocyclyloxy, or pharmaceutically acceptable salt thereof. (g-23) The compound of any one of the above (g-1) to (g-19), wherein R.sup.10ab is halogen, hydroxy, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkenyloxy, substituted or unsubstituted alkynyloxy, substituted or unsubstituted alkylsulfanyl, substituted or unsubstituted alkenylsulfanyl, substituted or unsubstituted alkynylsulfanyl, substituted or unsubstituted alkylamino, substituted or unsubstituted alkenylamino, or substituted or unsubstituted alkynylamino, or pharmaceutically acceptable salt thereof. (g-24) The compound of any one of the above (g-1) to (g-19), wherein R.sup.10ab is halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkylsulfanyl, or substituted or unsubstituted alkylamino, or pharmaceutically acceptable salt thereof. (g-25) The compound of any one of the above (g-1) to (g-19), wherein R.sup.10ab is halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy, or pharmaceutically acceptable salt, thereof. (g-26) The compound of any one of the above (g-1) to (g-19), wherein R.sup.10ab is halogen, alkyl, haloalkyl, alkyloxy, or haloalkyloxy, or pharmaceutically acceptable salt thereof. (g-27) The compound of any one of the above (g-1) to (g-19), wherein R.sup.10ab is halogen; cyano; alkyl substituted with one or more group(s) selected from halogen; unsubstituted alkyl; alkyloxy substituted with one or more group(s) selected from halogen; unsubstituted alkyloxy; alkylamino substituted with one or more group(s) selected from halogen; unsubstituted alkyloxy; non-aromatic heterocyclyl substituted with one or more group(s) selected from halogen; unsubstituted non-aromatic heterocyclyl; aromatic heterocyclyloxy substituted with one or more group(s) selected from halogen; or unsubstituted aromatic heterocyclyloxy,
or pharmaceutically acceptable salt thereof. (g-28) The compound of any one of the above (g-1) to (g-19), wherein R.sup.10ab is halogen; cyano; unsubstituted alkyl; alkyloxy substituted with one or more groups(s) selected from halogen; unsubstituted alkyloxy; unsubstituted alkylamino; unsubstituted non-aromatic heterocyclyl; or aromatic heterocyclyloxy substituted with one or more group(s) selected from halogen,
or pharmaceutically acceptable salt thereof. (g-29) The compound of any one of the above (g-1) to (g-19), wherein R.sup.10ab is halogen or pharmaceutically acceptable salt thereof. (g-30) The compound of any one of the above (g-1) to (g-19), wherein R.sup.10ab is a fluorine atom or a chlorine atom, or pharmaceutically acceptable salt thereof. (g-31) The compound of any one of the above (g-1) to (g-19), wherein R.sup.10ab is substituted or unsubstituted alkyl, or pharmaceutically acceptable salt thereof. (g-32) The compound of any one of the above (g-1) to (g-19), wherein R.sup.10ab is alkyl or haloalkyl, or pharmaceutically acceptable salt thereof. (g-33) The compound of any one of the above (g-1) to (g-19), wherein R.sup.10ab is substituted or unsubstituted alkyloxy, or pharmaceutically acceptable salt thereof. (g-34) The compound of any one of the above (g-1) to (g-19), wherein R.sup.10ab is alkyloxy or haloalkyloxy, or pharmaceutically acceptable salt thereof. (g-35) The compound of any one of the above (g-1) to (g-34), wherein R.sup.10ac is halogen, hydroxy, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkenyloxy, substituted or unsubstituted alkynyloxy, substituted or unsubstituted alkylsulfanyl, substituted or unsubstituted alkenylsulfonyl, substituted or unsubstituted alkynylsulfanyl, substituted or unsubstituted alkylamino, substituted or unsubstituted alkenylamino, substituted or unsubstituted alkynylamino, substituted or unsubstituted alkylcarbonyl, substituted or unsubstituted alkenylcarbonyl, substituted or unsubstituted alkynylcarbonyl, substituted or unsubstituted alkylsulfonyl, substituted or unsubstituted alkenylsulfonyl, substituted or unsubstituted alkynylsulfinyl, substituted or unsubstituted alkyloxycarbonyl, substituted or unsubstituted alkenyloxycarbonyl, substituted or unsubstituted alkynyloxycarbonyl, substituted or unsubstituted aryloxysulfonyl, substituted or unsubstituted alkenyloxysulfonyl, substituted or unsubstituted alkynyloxysulfonyl, substituted or unsubstituted aromatic carbocyclyl, substituted or unsubstituted non-aromatic carbocyclyl, substituted or unsubstituted aromatic heterocyclyl, substituted or unsubstituted non-aromatic heterocyclyl, substituted or unsubstituted aromatic carbocyclyloxy, substituted or unsubstituted non-aromatic carbocyclyloxy, substituted or unsubstituted aromatic heterocyclyloxy, substituted or unsubstituted non-aromatic heterocyclyloxy, substituted or unsubstituted aromatic carbocyclyl amino, substituted or unsubstituted non-aromatic carbocyclylamino, substituted or unsubstituted aromatic heterocyclylamino, substituted or unsubstituted non-aromatic heterocyclylamino, substituted or unsubstituted aromatic carbocyclylsulfanyl, substituted or unsubstituted non-aromatic carbocyclylsulfanyl, substituted or unsubstituted aromatic heterocyclylsulfanyl, or substituted or unsubstituted non-aromatic heterocyclyl sulfanyl, or pharmaceutically acceptable salt thereof. (g-36) The compound of any one of the above (g-1) to (g-34), wherein R.sup.10ac is halogen, hydroxy, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkylsulfanyl, substituted or unsubstituted alkylamino, substituted or unsubstituted alkylcarbonyl, substituted or unsubstituted alkylsulfonyl, substituted or unsubstituted alkyloxycarbonyl, substituted or unsubstituted aryloxysulfonyl, substituted or unsubstituted aromatic carbocyclyl, substituted or unsubstituted non-aromatic carbocyclyl, substituted or unsubstituted aromatic heterocyclyl, substituted or unsubstituted non-aromatic heterocyclyl, substituted or unsubstituted aromatic carbocyclyloxy, substituted or unsubstituted non-aromatic carbocyclyloxy, substituted or unsubstituted aromatic heterocyclyloxy, substituted or unsubstituted non-aromatic heterocyclyloxy, substituted or unsubstituted aromatic carbocyclylamino, substituted or unsubstituted non-aromatic carbocyclylamino, substituted or unsubstituted aromatic heterocyclylamino, substituted or unsubstituted non-aromatic heterocyclylamino, substituted or unsubstituted aromatic carbocyclylsulfanyl, substituted or unsubstituted non-aromatic carbocyclylsulfanyl, substituted or unsubstituted aromatic heterocyclylsulfanyl, or substituted or unsubstituted non-aromatic heterocyclylsulfanyl, or pharmaceutically acceptable salt thereof. (g-37) The compound of any one of the above (g-1) to (g-34), wherein R.sup.10ac is halogen, hydroxy, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkylsulfanyl, substituted or unsubstituted alkylamino, substituted or unsubstituted alkylcarbonyl, substituted or unsubstituted alkylsulfonyl, substituted or unsubstituted alkyloxycarbonyl, substituted or unsubstituted alkyloxysulfonyl, substituted or unsubstituted aromatic carbocyclyl, substituted or unsubstituted non-aromatic carbocyclyl, substituted or unsubstituted aromatic heterocyclyl, substituted or unsubstituted non-aromatic heterocyclyl, substituted or unsubstituted aromatic carbocyclyloxy, substituted or unsubstituted non-aromatic carbocyclyloxy, substituted or unsubstituted aromatic heterocyclyloxy, or substituted or unsubstituted non-aromatic heterocyclyloxy, or pharmaceutically acceptable salt thereof. (g-38) The compound of any one of the above (g-1) to (g-34), wherein R.sup.10ac is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkylsulfanyl, substituted or unsubstituted alkylsulfonyl, substituted or unsubstituted alkyloxycarbonyl, substituted or unsubstituted aromatic carbocyclyl, substituted or unsubstituted aromatic heterocyclyl, substituted or unsubstituted non-aromatic heterocyclyl, substituted or unsubstituted non-aromatic carbocyclyloxy, or substituted or unsubstituted aromatic heterocyclyloxy, or pharmaceutically acceptable salt thereof. (g-39)

(356) The compound of any one of the above (g-11 to (g-34), wherein R.sup.10ac is alkyl substituted with one or more group(s) selected from halogen, hydroxy, and non-aromatic heterocyclyl; unsubstituted alkyl; alkyl substituted with one or more group(s) selected from halogen, hydroxy, and non-aromatic heterocyclyl; unsubstituted alkenyl; alkyl substituted with one or more group(s) selected from halogen, hydroxy, and non-aromatic heterocyclyl; unsubstituted alkynyl: unsubstituted alkynyl; alkyloxy substituted with one or more group(s) selected from halogen, hydroxy, and non-aromatic heterocyclyl; unsubstituted alkyloxy: alkylsulfanyl substituted with one or more group(s) selected from halogen, hydroxy, and non-aromatic heterocyclyl; unsubstituted alkylsulfanyl; alkylsulfonyl substituted with one or more group(s) selected from halogen, hydroxy, and non-aromatic heterocyclyl; unsubstituted alkylsulfonyl: alkyloxycarbonyl substituted with one or more group(s) selected from halogen, hydroxy, and non-aromatic heterocyclyl; unsubstituted alkyloxycarbonyl; aromatic carbocyclyl substituted with one or more group (a) selected from alkyl, alkyloxy, and alkyloxycarbonyl; unsubstituted aromatic carbocyclyl: aromatic heterocyclyl substituted with one or more group(s) selected from alkyl, alkyloxy, and alkyloxycarbonyl; unsubstituted aromatic heterocyclyl; non-aromatic heterocyclyl substituted with one or more group(s) selected from alkyl, alkyloxy, and alkyloxycarbonyl; unsubstituted non-aromatic heterocyclyl; non-aromatic carbocyclyloxy substituted with one or more group(s) selected from alkyl, alkyloxy, and alkyloxycarbonyl; unsubstituted non-aromatic carbocyclyloxy; aromatic heterocyclyloxy substituted with one or more group(s) selected from alkyl, alkyloxy, and alkyloxycarbonyl; or unsubstituted aromatic heterocyclyloxy, or pharmaceutically acceptable salt thereof. (g-40) The compound of any one of the above (g-1) to (g-34), wherein R.sup.10ac is alkyl substituted with one or more group(s) selected from halogen, hydroxy, and non-aromatic heterocyclyl; unsubstituted alkyl; unsubstituted alkenyl; unsubstituted alkynyl; alkyloxy substituted with one or more group(s) selected from halogen; unsubstituted alkyloxy; alkylsulfanyl substituted with one or more group(s) selected from halogen; unsubstituted alkylsulfonyl; unsubstituted alkyloxycarbonyl: unsubstituted aromatic carbocyclyl; aromatic heterocyclyl substituted with one or more group(s) selected from alkyl and alkyloxy; unsubstituted aromatic heterocyclyl; non-aromatic heterocyclyl substituted with one or more group(s) selected from alkyl and alkyloxycarbonyl; unsubstituted non-aromatic heterocyclyl; unsubstituted non-aromatic carbocyclyloxy: or unsubstituted aromatic heterocyclyloxy,
or pharmaceutically acceptable salt thereof. (g-41) The compound of any one of the above (g-1) to (g-34), wherein R is halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkylsulfanyl, substituted or unsubstituted alkylamino, substituted or unsubstituted aromatic carbocyclyl, substituted or unsubstituted non-aromatic carbocyclyl, substituted or unsubstituted aromatic heterocyclyl, substituted or unsubstituted non-aromatic heterocyclyl, substituted or unsubstituted aromatic carbocyclyloxy, substituted or unsubstituted non-aromatic carbocyclyloxy, substituted or unsubstituted aromatic heterocyclyloxy, or substituted or unsubstituted non-aromatic heterocyclyloxy, or pharmaceutically acceptable salt thereof. (g-42) The compound of any one of the above (g-1) to (g-34), wherein R.sup.10ac is halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted aromatic heterocyclyl, substituted or unsubstituted non-aromatic heterocyclyl, substituted or unsubstituted aromatic heterocyclyloxy, or substituted or unsubstituted non-aromatic heterocyclyloxy, or pharmaceutically acceptable salt, thereof. (g-43) The compound of any one of the above (g-1) to (g-34), wherein R.sup.10ac is halogen; alkyl; haloalkyl; alkyloxy; haloaryloxy; aromatic heterocyclyl substituted with one or more group(s) selected from halogen, alkyl, haloalkyl, alkyloxy, and haloaryloxy; unsubstituted aromatic heterocyclyl; non-aromatic heterocyclyl substituted with one or more group(s) selected from halogen, alkyl, haloalkyl, alkyloxy, and haloaryloxy; unsubstituted non-aromatic heterocyclyl; aromatic heterocyclyloxy substituted with one or more group(s) selected from halogen, alkyl, haloalkyl, alkyloxy, and haloaryloxy; or unsubstituted aromatic heterocyclyloxy, or pharmaceutically acceptable salt thereof. (g-44) The compound of any one of the above (g-1) to (g-34), wherein R.sup.10ac is halogen, or pharmaceutically acceptable salt thereof. (g-45) The compound of any one of the above (g-1) to (g-34), wherein R.sup.10ac is a fluorine atom or a chlorine atom, or pharmaceutically acceptable salt thereof. (g-46) The compound of any one of the above (g-1) to (g-34), wherein R.sup.10ac is substituted or unsubstituted alkyl, or pharmaceutically acceptable salt thereof. (g-47) The compound of any one of the above (g-1) to (g-34), wherein R.sup.10ac is alkyl or haloalkyl, or pharmaceutically acceptable salt thereof. (g-48) The compound of any one of the above (g-1) to (g-34), wherein R.sup.10ac is substituted or unsubstituted alkyloxy, or pharmaceutically acceptable salt thereof. (g-49) The compound of any one of the above (g-1) to (g-34), wherein R.sup.10ac is alkyloxy or haloaryloxy, or pharmaceutically acceptable salt thereof. (g-50) The compound of any one of the above (g-1) to (g-34), wherein R.sup.10ac is substituted or unsubstituted aromatic heterocyclyl or substituted or unsubstituted nonaromatic heterocyclyl, or pharmaceutically acceptable salt thereof. (g-51) The compound of any one of the above (g-1) to (g-34), wherein R.sup.10ac is substituted or unsubstituted aromatic heterocyclyloxy or substituted or unsubstituted non-aromatic heterocyclyloxy, or pharmaceutically acceptable salt thereof. (h) A compound according to any one of the following (h-1) to (h-34) or a pharmaceutically acceptable salt thereof. (h-1) The compound of any one of Formula (I) and the above (a) to (e), wherein R.sup.3 is a group represented by the formula:

(357) ##STR00062##
wherein Ring F1 and Ring F2 are each independently a substituted or unsubstituted 5-membered non-aromatic carbocycle, a substituted or unsubstituted 5-membered aromatic heterocycle, or a substituted or unsubstituted 5-membered non-aromatic heterocycle; Ring G1 and Ring G2 are each independently a substituted or unsubstituted 6-membered aromatic carbocycle, a substituted or unsubstituted 6-membered non-aromatic carbocycle, a substituted or unsubstituted 6-membered aromatic heterocycle, or a substituted or unsubstituted 6-membered non-aromatic heterocycle: Ring H1 is a substituted or unsubstituted 6-membered aromatic carbocycle, a substituted or unsubstituted 6-membered non-aromatic carbocycle, a substituted or unsubstituted 6-membered aromatic heterocycle, or a substituted or unsubstituted 6-membered non-aromatic heterocycle: p1b and p1c are each independently 0 or 1; R.sup.9a and R.sup.9b are the same as the above (f-1); and R.sup.10a1 is the same as R.sup.10a of the above (f-1),
or pharmaceutically acceptable salt thereof.

(358) The above definition of R.sup.3 means that R.sup.10a1 is a substituent on Ring B. (h-2) The compound of any one of Formula (I) and the above (a) to (e), wherein R.sup.3 is

(359) ##STR00063##
or pharmaceutically acceptable salt thereof. (h-3) The compound of any one of Formula (I) and the above (a) to (e), wherein R.sup.3 is

(360) ##STR00064##
or pharmaceutically acceptable salt thereof. (h-4) The compound of any one of Formula (I) and the above (a) to (e), wherein R.sup.3 is

(361) ##STR00065##
or pharmaceutically acceptable salt thereof. (h-5) The compound of any one of Formula (I) and the above (a) to (e), wherein R.sup.3 is

(362) ##STR00066##
or pharmaceutically acceptable salt thereof. (h-6) The compound of any one of Formula (I) and the above (a) to (e), wherein R.sup.3 is

(363) ##STR00067##
or pharmaceutically acceptable salt thereof. (h-7) The compound of any one of Formula (I) and the above (a) to (e), wherein R.sup.3 is

(364) ##STR00068##
or pharmaceutically acceptable salt, thereof. (h-8) The compound of any one of the above (h-1) to (h-7), wherein Ring F1 is substituted or unsubstituted cyclopentane, substituted or unsubstituted furan, substituted or unsubstituted thiophene, substituted or unsubstituted pyrrole, substituted or unsubstituted pyrazole, substituted or unsubstituted imidazole, substituted or unsubstituted thiazole, substituted or unsubstituted oxazole, substituted or unsubstituted dihydrofuran, substituted or unsubstituted dihydrothiophene, substituted or unsubstituted dihydropyrrole, or substituted or unsubstituted dioxolo, or pharmaceutically acceptable salt thereof. (h-9) The compound of any one of the above (h-1) to (h-7), wherein Ring F1 is substituted or unsubstituted cyclopentane, substituted or unsubstituted furan, substituted or unsubstituted pyrrole, substituted or unsubstituted pyrazole, substituted or unsubstituted thiazole, substituted or unsubstituted oxazole, substituted or unsubstituted dihydrofuran, or substituted or unsubstituted dioxole, or pharmaceutically acceptable salt thereof. (h-10) The compound of any one of the above (h-1) to (h-7), wherein Ring F1 is cyclopentane substituted with one or more group(s) selected from halogen and alkyl; unsubstituted cyclopentane; furan substituted with one or more group(s) selected from halogen and alkyl; unsubstituted furan; pyrrole substituted with one or more group(s) selected from halogen and alkyl; unsubstituted pyrrole; pyrazole substituted with one or more group(s) selected from halogen and alkyl; unsubstituted pyrazole; thiazole substituted with one or more group(s) selected from halogen and alkyl; unsubstituted thiazole; oxazole substituted with one or more group(s) selected from halogen and alkyl; unsubstituted oxazole; dihydrofuran substituted with one or more group(s) selected from halogen and alkyl; unsubstituted dihydrofuran; dioxole substituted with one or more group(s) selected from halogen and alkyl; or unsubstituted dioxole,
or pharmaceutically acceptable salt thereof. (b-11) The compound of any one of the above (h-1) to (h-7), wherein Ring F1 is unsubstituted cyclopentane; furan substituted with one or more group(s) selected from alkyl; unsubstituted pyrrole; unsubstituted pyrazole; thiazole substituted with one or more group(s) selected from alkyl; unsubstituted oxazole; unsubstituted dihydrofuran; dioxole substituted with one or more group(s) selected from halogen; or unsubstituted dioxole, or pharmaceutically acceptable salt thereof. (h-12) The compound of any one of the above (h-1) to (h-7), wherein Ring F2 is substituted or unsubstituted cyclopentane, substituted or unsubstituted furan, substituted or unsubstituted thiophene, substituted or unsubstituted pyrrole, substituted or unsubstituted pyrazole, substituted or unsubstituted imidazole, substituted or unsubstituted thiazole, substituted or unsubstituted oxazole, substituted or unsubstituted dihydrofuran, substituted or unsubstituted dihydrothiophene, or substituted or unsubstituted dihydropyrrole, or pharmaceutically acceptable salt thereof. (h-13) The compound of any one of the above (h-1) to (h-7), wherein Ring F2 is substituted or unsubstituted furan, substituted or unsubstituted pyrrole, substituted or unsubstituted thiazole, or substituted or unsubstituted dihydrofuran, or pharmaceutically acceptable salt, thereof. (h-4) The compound of any one of the above (h-1) to (h-7), wherein Ring F2 is furan substituted with one or more group(s) selected from alkyl and alkyloxy; unsubstituted furan; pyrrole substituted with one or more group(s) selected from alkyl and alkyloxy; unsubstituted pyrrole; thiazole substituted with one or more group(s) selected from alkyl and alkyloxy; unsubstituted thiazole; dihydrofuran substituted with one or more group(s) selected from alkyl and alkyloxy; or unsubstituted dihydrofuran,
or pharmaceutically acceptable salt thereof. (h-15) The compound of any one of the above (h-1) to (h-7), wherein Ring F2 is furan substituted with one or more group(s) selected from alkyl; unsubstituted furan; unsubstituted pyrrole; thiazole substituted with one or more group(s) selected from alkyl and alkyloxy; unsubstituted thiazole; or unsubstituted dihydrofuran, or pharmaceutically acceptable salt thereof. (h-16) The compound of any one of the above (h-1) to (e-15), wherein Ring G1, and Ring G2 are each independently substituted or unsubstituted benzene, substituted or unsubstituted cyclohexane, substituted or unsubstituted pyridine, substituted or unsubstituted pyrazine, substituted or unsubstituted pyrimidine, substituted or unsubstituted pyran, substituted or unsubstituted dihydropyran, substituted or unsubstituted dihydropyridine, substituted or unsubstituted tetrahydropyridine, substituted or unsubstituted dihydropyrazine, substituted or unsubstituted tetrahydropyrazine, substituted or unsubstituted oxazine, substituted or unsubstituted dihydrooxazine, substituted or unsubstituted dioxin, or substituted or unsubstituted dihydrodioxin, or pharmaceutically acceptable salt thereof. (h-17) The compound of any one of the above (h-1) to (h-15), wherein Ring G1 and Ring G2 are each independently substituted or unsubstituted pyridine, substituted or unsubstituted pyrazine, substituted or unsubstituted pyrimidine, substituted or unsubstituted pyran, substituted or unsubstituted dihydropyran, or substituted or unsubstituted dihydrodioxin, or pharmaceutically acceptable salt thereof. (h-18) The compound of any one of the above (h-1) to (h-15), wherein Ring G1 and Ring (12 are each independently substituted or unsubstituted pyridine, substituted or unsubstituted pyran, substituted or unsubstituted dihydropyran, or substituted or unsubstituted dihydrodioxin, or pharmaceutically acceptable salt thereof. (h-19) The compound of any one of the above (h-1) to (h-15), wherein Ring G1 and Ring G2 are each independently pyridine substituted with one or more group(s) selected from halogen; unsubstituted pyridine: pyran substituted with one or more group(s) selected from halogen; unsubstituted pyran; dihydropyran substituted with one or more group(s) selected from halogen; unsubstituted dihydropyran; dihydrodioxin substituted with one or more group(s) selected from halogen; or unsubstituted dihydrodioxin,
or pharmaceutically acceptable salt thereof. (h-20) The compound of any one of the above (h-1) to (h-15), wherein Ring G1 and Ring G2 are each independently unsubstituted pyridine; unsubstituted pyran; unsubstituted dihydropyran; dihydrodioxin substituted with one or more group(s) selected from halogen; or unsubstituted dihydrodioxin, or pharmaceutically acceptable salt thereof. (h-21) The compound of any one of the above (h-1) to (h-20), wherein Ring H1 is substituted or unsubstituted benzene, substituted or unsubstituted cyclohexane, substituted or unsubstituted pyridine, substituted or unsubstituted pyrazine, substituted or unsubstituted pyrimidine, or pharmaceutically acceptable salt thereof. (h-22) The compound of any one of the above (h-1) to (h-20), wherein Ring H1 is each independently substituted or unsubstituted benzene, or pharmaceutically acceptable salt thereof. (h-23) The compound of any one of the above (h-1) to (h-20), wherein Ring H1 is benzene substituted with one or more group(s) selected from halogen, or pharmaceutically acceptable salt thereof. (h-24) The compound of any one of the above (h-1) to (h-20), wherein Ring H1 is unsubstituted benzene, or pharmaceutically acceptable salt thereof. (h-25) The compound of any one of the above (h-1) to (h-24), wherein p1b is 0, or pharmaceutically acceptable salt thereof. (h-26) The compound of any one of the above (h-1) to (h-24), wherein p1b is 1, or pharmaceutically acceptable salt thereof. (h-27) The compound of any one of the above (h-1) to (h-26), wherein p1c is 0, or pharmaceutically acceptable salt thereof. (h-28) The compound of any one of the above (h-1) to (h-26), wherein p1c is 1, or pharmaceutically acceptable salt thereof.

(365) (h-29) The compound of any one of the above (h-1) to (h-28), wherein R.sup.10a1 is halogen, hydroxy, amino, carbamoyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkenyloxy, substituted or unsubstituted alkynyloxy, substituted or unsubstituted alkylsulfanyl, substituted or unsubstituted alkenylsulfonyl, substituted or unsubstituted alkynylsulfanyl, substituted or unsubstituted alkylamino, substituted or unsubstituted alkenylamino, or substituted or unsubstituted alkynylamino, or pharmaceutically acceptable salt thereof. (h-80) The compound of any one of the above (h-1) to (h-28), wherein R.sup.10a1 is halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkylsulfanyl, or substituted or unsubstituted alkylamino, or pharmaceutically acceptable salt thereof. (h-31) The compound of any one of the above (h-1) to (h-28), wherein R.sup.10a halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy, or pharmaceutically acceptable salt thereof. (h-32) The compound of any one of the above (h-1) to (h-28), wherein R.sup.10a1 is halogen, alkyl, haloalkyl, alkyloxy, or haloalkyloxy, or pharmaceutically acceptable salt thereof. (h-33) The compound of any one of the above (h-1) to (h-28), wherein R.sup.10a1 is unsubstituted or unsubstituted alkyl, or pharmaceutically acceptable salt thereof. (h-34) The compound of any one of the above (h-1) to (h-28), wherein R.sup.10a1 is unsubstituted alkyl, or pharmaceutically acceptable salt thereof. (i) A compound according to any one of the following (i-1) to (i-16) or a pharmaceutically acceptable salt thereof. (i-1) The compound of any one of Formula (I) and the above (a) to (h), wherein R.sup.9a and R.sup.9b are each independently halogen, hydroxy, amino, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkenyloxy, substituted or unsubstituted alkynyloxy, substituted or unsubstituted alkylsulfanyl, substituted or unsubstituted alkenylsulfanyl, substituted or unsubstituted alkynylsulfanyl, substituted or unsubstituted alkylamino, substituted or unsubstituted alkenylamino, substituted or unsubstituted alkynylamino, substituted or unsubstituted aromatic carbocyclyl, substituted or unsubstituted non-aromatic carbocyclyl, substituted or unsubstituted aromatic heterocyclyl, substituted or unsubstituted non-aromatic heterocyclyl, substituted or unsubstituted aromatic carbocyclyloxy, substituted nr unsubstituted non-aromatic carbocyclyloxy, substituted or unsubstituted aromatic heterocyclyloxy, or substituted or unsubstituted non-aromatic heterocyclyloxy, or pharmaceutically acceptable salt thereof. (i-2) The compound of any one of Formula (I) and the above (a) to (h), wherein R.sup.9a and R.sup.9b are each independently halogen, hydroxy, amino, substituted or unsubstituted alkyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkylsulfanyl, substituted or unsubstituted alkylamino, substituted or unsubstituted aromatic carbocyclyl, substituted or unsubstituted non-aromatic carbocyclyl, substituted or unsubstituted aromatic heterocyclyl, substituted or unsubstituted non-aromatic heterocyclyl, substituted or unsubstituted aromatic carbocyclyloxy, substituted or unsubstituted non-aromatic carbocyclyloxy, substituted or unsubstituted aromatic heterocyclyloxy, or substituted or unsubstituted non-aromatic heterocyclyloxy, or pharmaceutically acceptable salt thereof. (i-3) The compound of any one of Formula (I) and the above (a) to (h), wherein R.sup.9a and R.sup.9b are each independently halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkylsulfanyl, substituted or unsubstituted alkylamino, substituted or unsubstituted aromatic carbocyclyl, or substituted or unsubstituted aromatic carbocyclyloxy, or pharmaceutically acceptable salt thereof. (i-4) The compound of any one of Formula (I) and the above (a) to (h), wherein R.sup.9a and R.sup.9b are each independently halogen; alkyl substituted with one or more group(s) selected from halogen, alkyloxy, aromatic carbocyclyl, and aromatic heterocyclyl; unsubstituted alkyl; alkyloxy substituted with one or more group(s) selected from halogen, alkyloxy, aromatic carbocyclyl, and aromatic heterocyclyl; unsubstituted alkyloxy; alkylsulfanyl substituted with one or more group (a) selected from halogen, alkyloxy, aromatic carbocyclyl, and aromatic heterocyclyl; unsubstituted alkylsulfanyl; alkylamino substituted with one or more group(s) selected from halogen, alkyloxy, aromatic carbocyclyl, and aromatic heterocyclyl; unsubstituted alkylamino; aromatic carbocyclyl substituted with one or more group(s) selected from halogen, alkyl, and alkyloxy; unsubstituted aromatic carbocyclyl; aromatic carbocyclyloxy substituted with one or more group(s) selected from halogen, alkyl, and alkyloxy; or unsubstituted aromatic carbocyclyloxy,
or pharmaceutically acceptable salt thereof. (i-5) The compound of any one of Formula (I) and the above (a) to (h), wherein R.sup.9a and R.sup.9b are each independently halogen; alkyl substituted with one or more group(s) selected from halogen, alkyloxy, aromatic carbocyclyl, and aromatic heterocyclyl; unsubstituted alkyl; alkyloxy substituted with one or more group(s) selected from halogen; unsubstituted alkyloxy; unsubstituted alkylsulfanyl; unsubstituted alkylamino; unsubstituted aromatic carbocyclyl: aromatic carbocyclyloxy substituted with one or more group(s) selected from alkyl; or unsubstituted aromatic carbocyclyloxy,
or pharmaceutically acceptable salt thereof. (i-6) The compound of any one of Formula U) and the above (a) to (h), wherein R.sup.9a and R.sup.9b are each independently halogen; alkyl substituted with one or more group(s) selected from halogen, alkyloxy, aromatic carbocyclyl, and aromatic heterocyclyl; or unsubstituted alkyl, or pharmaceutically acceptable salt thereof. (i-7) The compound of any one of Formula (I) and the above (a) to (h), wherein R.sup.9a and R.sup.9b are each independently halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkenyloxy, substituted or unsubstituted alkynyloxy, substituted or unsubstituted alkylsulfanyl, substituted or unsubstituted alkenylsulfonyl, substituted or unsubstituted alkynylsulfanyl, substituted or unsubstituted alkylamino, substituted or unsubstituted alkenylamino, or substituted or unsubstituted alkynylamino, or pharmaceutically acceptable salt thereof. (i-8) The compound of any one of Formula (L) and the above (a) to (h), wherein R.sup.9a and R.sup.9b are each independently halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkylsulfanyl, or substituted or unsubstituted alkylamino, or pharmaceutically acceptable salt thereof. (i-9) The compound of any one of Formula (I) and the above (a) to (h), wherein R.sup.9a and R.sup.9b are each independently halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted alkylsulfanyl, or pharmaceutically acceptable salt thereof. (i-10) The compound of any one of Formula (I) and the above (a) to (h), wherein R.sup.9a and R.sup.9b are each independently halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, or substituted or unsubstituted alkynyl, or pharmaceutically acceptable salt thereof. (i-11) The compound of any one of Formula (I) and the above (a) to (h), wherein R.sup.9a and R.sup.9b are each independently halogen, or substituted or unsubstituted alkyl, or pharmaceutically acceptable salt thereof. (i-12) The compound of any one of Formula (I) and the above (a) to (h), wherein R.sup.9a and R.sup.9b are each independently halogen, or substituted or unsubstituted alkyl, or pharmaceutically acceptable salt thereof. (i-13) The compound of any one of Formula (I) and the above (a) to (h), wherein R.sup.9a and R.sup.9b are each independently halogen, alkyl, or haloalkyl, or pharmaceutically acceptable salt thereof. (i-14) The compound of any one of Formula (I) and the above (a) to (h), wherein R.sup.9a and R.sup.9b are each independently substituted or unsubstituted C1 to C3 alkyl, or pharmaceutically acceptable salt thereof. (i-1.5) The compound of any one of Formula (I) and the above (a) to (h), wherein R.sup.9a and R.sup.9b are each independently unsubstituted C1 to C3 alkyl, or pharmaceutically acceptable salt thereof. (i-16) The compound of any one of Formula (I) and the above (a) to (h), wherein R.sup.9a and R.sup.9b are each independently unsubstituted methyl or unsubstituted ethyl, or pharmaceutically acceptable salt, thereof. (j) A compound according to any one of the following (j-1) to (j-30) or a pharmaceutically acceptable salt thereof. (j-1) The compound of any one of Formula (I) and the above (a) to (e), wherein R.sup.3 is a group represented by the Formula:

(366) ##STR00069##
wherein Ring F3 is a substituted or unsubstituted 5-membered non-aromatic carbocycle, a substituted or unsubstituted 5-membered aromatic heterocycle, or a substituted or unsubstituted 5-membered non-aromatic heterocycle: Ring G3 is a substituted or unsubstituted 6-membered aromatic carbocycle, a substituted or unsubstituted 6-membered non-aromatic carbocycle, a substituted or unsubstituted 6-membered aromatic heterocycle, or a substituted or unsubstituted (i-membered non-aromatic heterocycle-. Ring H2 is a substituted or unsubstituted 6-membered aromatic carbocycle, a substituted or unsubstituted 6-membered non-aromatic carbocycle, a substituted or unsubstituted 6-membered aromatic heterocycle, or a substituted or unsubstituted 6-membered non-aromatic heterocycle; p1d and p2b are each independently 0 or 1; and R.sup.10a2 and R.sup.10b1 are the same as R.sup.10a and R.sup.10b of the above (f-1),
or pharmaceutically acceptable salt thereof. (j-2) The compound of any one of Formula (I) and the above (a) to (e), wherein R.sup.3 is

(367) ##STR00070##
or pharmaceutically acceptable salt thereof. (j-3) The compound of any one of Formula (I) and the above (a) to (e), wherein R.sup.3 is

(368) ##STR00071##
or pharmaceutically acceptable salt thereof. (j-4) The compound of any one of Formula (I) and the above (a) to (e), wherein R.sup.3 is

(369) ##STR00072##
or pharmaceutically acceptable salt thereof. (j-5) The compound of any one of the above (j-1) to (j-4), wherein Ring F3 is substituted or unsubstituted cyclopentane, substituted or unsubstituted furan, substituted or unsubstituted thiophene, substituted or unsubstituted pyrrole, substituted or unsubstituted pyrazole, substituted or unsubstituted imidazole, substituted or unsubstituted thiazole, substituted or unsubstituted oxazole, substituted or unsubstituted dihydrofuran, substituted or unsubstituted dihydrothiophene, substituted or unsubstituted dihydropyrrole, or substituted or unsubstituted dioxole, or pharmaceutically acceptable salt thereof. (j-6) The compound of any one of the above (j-1) to (j-4), wherein Ring F3 is cyclopentane substituted with one or more group(s) selected from alkyl; unsubstituted cyclopentane; furan substituted with one or more group(s) selected from alkyl; unsubstituted furan; thiophene substituted with one or more group(s) selected from alkyl; unsubstituted thiophene; pyrrole substituted with one or more group(s) selected from alkyl; unsubstituted pyrrole: imidazole substituted with one or more group(s) selected from alkyl; unsubstituted imidazole; thiazole substituted with one or more group(s) selected from alkyl; unsubstituted thiazole: oxazole substituted with one or more group(s) selected from alkyl; unsubstituted oxazole; dihydrofuran substituted with one or more group(s) selected from alkyl; unsubstituted dihydrofuran; dioxole substituted with one or more group(s) selected from alkyl; or unsubstituted dioxole,
or pharmaceutically acceptable salt thereof. (j-7) The compound of any one of the above (j-1) to (j-4), wherein Ring F3 is unsubstituted cyclopentane; unsubstituted furan: unsubstituted thiophene; pyrrole substituted with one or more group(s) selected from alkyl and an aromatic carbocycle; unsubstituted pyrrole; unsubstituted imidazole; unsubstituted thiazole; unsubstituted oxazole; unsubstituted dihydrofuran;
or unsubstituted dioxole, or pharmaceutically acceptable salt thereof. (j-8) The compound of any one of the above (j-1) to (j-4), wherein Ring F3 is substituted or unsubstituted cyclopentane, substituted or unsubstituted furan, substituted or unsubstituted thiophene, substituted or unsubstituted pyrrole, or substituted or unsubstituted dihydrofuran, or pharmaceutically acceptable salt thereof. (j-9) The compound of any one of the above (j-1) to (j-4), wherein Ring F3 is substituted or unsubstituted furan, substituted or unsubstituted thiophene, or substituted or unsubstituted pyrrole, or pharmaceutically acceptable salt thereof. (j-10) The compound of any one of the above (j-1) to (j-4), wherein Ring F3 is furan substituted with one or more group(s) selected from alkyl; unsubstituted furan; thiophene substituted with one or more group(s) selected from alkyl; unsubstituted thiophene: pyrrole substituted with one or more group(s) selected from alkyl; or unsubstituted pyrrole, or pharmaceutically acceptable salt thereof. (j-11) The compound of any one of the above (j-1) to (j-4), wherein Ring F3 is substituted furan: unsubstituted thiophene; pyrrole substituted with one or more group(s) selected from alkyl; or unsubstituted pyrrole, or pharmaceutically acceptable salt thereof. (j-12) The compound of any one of the above (j-1) to (j-11), wherein Ring G3 is substituted or unsubstituted benzene, substituted or unsubstituted cyclohexane, substituted or unsubstituted pyridine, substituted or unsubstituted pyrazine, substituted or unsubstituted pyrimidine, substituted or unsubstituted pyran, substituted or unsubstituted dihydropyran, substituted or unsubstituted dihydropyridine, substituted or unsubstituted tetrahydropyridine, substituted or unsubstituted dihydropyrazine, substituted or unsubstituted tetrahydropyrazine, substituted or unsubstituted oxazine, substituted or unsubstituted dihydrooxazine, substituted or unsubstituted dioxin, or substituted or unsubstituted dihydrodioxin, or pharmaceutically acceptable salt thereof. (j-13) The compound of any one of the above (j-1) to (j-11), wherein Ring G3 is substituted or unsubstituted cyclohexane, substituted or unsubstituted dihydropyridine, substituted or unsubstituted tetrahydropyridine, or substituted or unsubstituted dihydrodioxin, or pharmaceutically acceptable salt thereof. (j-14) The compound of any one of the above (j-1) to (j-11), wherein Ring G3 is cyclohexane substituted with one or more group(s) selected from alkyl; unsubstituted cyclohexane; dihydropyridine substituted with one or more group(s) selected from alkyl; unsubstituted dihydropyridine; tetrahydropyridine substituted with one or more group(s) selected from alkyl; unsubstituted tetrahydropyridine: dihydrodioxin substituted with one or more group(s) selected from alkyl; or unsubstituted dihydrodioxin,
or pharmaceutically acceptable salt thereof. (j-15) The compound of any one of the above (j-1) to (j-11), wherein Ring (<3 is unsubstituted cyclohexane; dihydropyridine substituted with one or more group(s) selected from alkyl; unsubstituted dihydropyridine; unsubstituted tetrahydropyridine, or unsubstituted dihydrodioxin, or pharmaceutically acceptable salt thereof. (j-16) The compound of any one of the above (j-1) to (j-11), wherein Ring G3 is unsubstituted cyclohexane; dihydropyridine substituted with one or more group(s) selected from alkyl; or unsubstituted dihydropyridine, or pharmaceutically acceptable salt thereof. (j-17) The compound of any one of the above (j-1) to (j-16), wherein Ring H2 is substituted or unsubstituted benzene, substituted or unsubstituted cyclohexane, substituted or unsubstituted pyridine, substituted or unsubstituted pyrazine, substituted or unsubstituted pyrimidine, or pharmaceutically acceptable salt, thereof. (j-18) The compound of any one of the above (j-1) to (j-16), wherein Ring H2 is each independently substituted or unsubstituted benzene, or pharmaceutically acceptable salt thereof. (j-19) The compound of any one of the above (j-1) to (j-16), wherein Ring H2 is benzene substituted with one or more group(s) selected from halogen, or pharmaceutically acceptable salt, thereof. (j-20) The compound of any one of the above (j-1) to (j-16), wherein Ring H2 is unsubstituted benzene, or pharmaceutically acceptable salt thereof. (j-21) The compound of any one of the above (j-1) to (j-20), wherein p1d is 0, or pharmaceutically acceptable salt thereof. (j-22) The compound of any one of the above (j-1) to (j-20), wherein p1d is 1, or pharmaceutically acceptable salt thereof. (j-23) The compound of any one of the above (j-1) to (j-22), wherein p2b is 0, or pharmaceutically acceptable salt thereof. (j-24) The compound of any one of the above (j-1) to (j-22), wherein p2b is 1, or pharmaceutically acceptable salt thereof. (j-25) The compound of any one of the above (j-1) to (j-21), wherein R.sup.10a2 and R.sup.10b1 are each independently halogen, hydroxy, amino, carbamoyl, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkenyloxy, substituted or unsubstituted alkynyloxy, substituted or unsubstituted alkylsulfanyl, substituted or unsubstituted alkenylsulfanyl, substituted or unsubstituted alkynylsulfanyl, substituted or unsubstituted alkylamino, substituted or unsubstituted alkenylamino, or substituted or unsubstituted alkynylamino, or pharmaceutically acceptable salt thereof. (j-26) The compound of any one of the above (j-1) to (j-24), wherein R.sup.10a2 and R.sup.10b1 are each independently halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkylsulfanyl, or substituted or unsubstituted alkylamino, or pharmaceutically acceptable salt thereof. (j-27) The compound of any one of the above (j-1) to (j-24), wherein R.sup.10a1 and R.sup.10b1 are each independently halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy, or pharmaceutically acceptable salt thereof. (j-28) The compound of any one of the above (j-1) to (j-24), wherein R.sup.10a2 and R.sup.10b1 are each independently halogen, alkyl, haloalkyl, alkyloxy, or haloaryloxy, or pharmaceutically acceptable salt thereof. (j-29) The compound of any one of the above (j-1) to (j-24), wherein R.sup.10a2 and R.sup.10b1 are each independently halogen or unsubstituted or unsubstituted alkyl, or
pharmaceutically acceptable salt thereof. (j-30) The compound of any one of the above (j-1) to (j-24), wherein R.sup.10a2 and R.sup.10b1 are each independently halogen or unsubstituted alkyl, or pharmaceutically acceptable salt thereof. (k) A compound according to any one of the following (k-1) to (k-11) or a pharmaceutically acceptable salt thereof. (k 1) The compound of any one of Formula (I) and the above (a) to (e), wherein R.sup.3 is

(370) ##STR00073##
or pharmaceutically acceptable salt thereof.

(371) The above definition of R.sup.3 means that R.sup.10c is a substituent, on Ring B, and R.sup.10e is a substituent on Ring D. (k-2) The compound of any one of Formula (I) and the above (a) to (e), wherein R.sup.3 is

(372) ##STR00074##
or pharmaceutically acceptable salt thereof. (k-3) The compound of the above (k-1) or (k-2), wherein R.sup.10c and R.sup.10d are each independently halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkenyloxy, substituted or unsubstituted alkynyloxy, substituted or unsubstituted aromatic carbocyclyl, substituted or unsubstituted non-aromatic carbocyclyl, substituted or unsubstituted aromatic heterocyclyl, substituted or unsubstituted non-aromatic heterocyclyl, substituted or unsubstituted aromatic carbocyclyloxy, substituted or unsubstituted non-aromatic carbocyclyloxy, substituted or unsubstituted aromatic heterocyclyloxy, or substituted or unsubstituted non-aromatic heterocyclyloxy, or pharmaceutically acceptable salt thereof. (k-4) The compound of the above (k-1) or (k-2), wherein R.sup.10c and R.sup.10d are each independently halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted aromatic carbocyclyl, substituted or unsubstituted non-aromatic carbocyclyl, substituted or unsubstituted aromatic heterocyclyl, substituted or unsubstituted non-aromatic heterocyclyl, substituted or unsubstituted aromatic carbocyclyloxy, substituted or unsubstituted non-aromatic carbocyclyloxy, substituted or unsubstituted aromatic heterocyclyloxy, or substituted or unsubstituted non-aromatic heterocyclyloxy, or pharmaceutically acceptable salt thereof. (k-5) The compound of the above (k-1) or (k-2), wherein R.sup.10c and R.sup.10d are each independently halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkyloxy, or pharmaceutically acceptable salt thereof. (k-6) The compound of the above (k-1) or (k-2), wherein R.sup.10c and R.sup.10d are each independently halogen, alkyl, haloalkyl, alkyloxy, haloalkyloxy, or pharmaceutically acceptable salt thereof. (k-7) The compound of the above (k-1) or (k-2), wherein R.sup.10c and R.sup.10d are each independently halogen, or pharmaceutically acceptable salt thereof. (k-8) The compound of any one of the above (k-1) to (k-7), wherein R.sup.10e is each independently halogen, or substituted or unsubstituted alkyl, or pharmaceutically acceptable salt thereof. (k-9) The compound of any one of the above (k-1) to (k-7), wherein R.sup.10e is each independently halogen, alkyl, or haloalkyl, or pharmaceutically acceptable salt thereof. (k-10) The compound of any one of the above (k-1) to (k-7), wherein R.sup.10e is each independently halogen, or pharmaceutically acceptable salt thereof. (k-11) The compound of any one of the above (k-1) to (k-10), wherein p3 is 0, or pharmaceutically acceptable salt thereof. (l) A compound according to any one of the following (l-1) to (l-6) or a pharmaceutically acceptable salt thereof. (l-1) The compound of any one of Formula (I) and the above (a) to (k), wherein Ring B is benzene, cyclohexene, or a 6-membered aromatic heterocycle, or pharmaceutically acceptable salt thereof. (l-2) The compound of any one of Formula (I) and the above (a) to (k), wherein Ring B is benzene, or a 6-membered aromatic heterocycle, or pharmaceutically acceptable salt thereof. (l-3) The compound of any one of Formula (I) and the above (a) to (k), wherein Ring B is benzene, cyclohexene, pyridine, pyrimidine, or pyrazine, or pharmaceutically acceptable salt, thereof. (l-4) The compound of any one of Formula (I) and the above (a) to (k), wherein Ring B is benzene, pyridine, pyrimidine, or pyrazine, or pharmaceutically acceptable salt thereof. (l-5) The compound of any one of Formula (I) and the above (a) to (k), wherein Ring B is benzene, or pyridine, or pharmaceutically acceptable salt thereof. (l-6) The compound of any one of Formula (I) and the above (a) to (k), wherein Ring B is benzene, or pharmaceutically acceptable salt thereof. (m) A compound according to any one of the following (m-1) to (m-4) or a pharmaceutically acceptable salt thereof. (m-1) The compound of any one of Formula (I) and the above (a) to (l), wherein Ring C is cyclopentane, or a 5-membered aromatic heterocycle, or pharmaceutically acceptable; salt thereof. (m-2) The compound of any one of Formula (I) and the above (a) to (l), wherein Ring C is a 5-membered aromatic heterocycle, or pharmaceutically acceptable salt thereof. (m-3) The compound of any one of Formula (I) and the above (a) to (l), wherein Ring C is cyclopentane, pyrrole, imidazole, pyrazole, furan, thiophene, isoxazole, oxazole, isothiazole, or thiazole, or pharmaceutically acceptable salt thereof. (m-4) The compound of any one of Formula (I) and the above (a) to (l), wherein Ring C is thiophene, or pharmaceutically acceptable salt thereof. (n) A compound according to any one of the following (n-1) to (n-19) or a pharmaceutically acceptable salt thereof. (n-1) The compound of any one of Formula (I) and the above (a) to (m), wherein R.sup.5a is a hydrogen atom, halogen, hydroxy, carboxy, amino, carbamoyl, sulfamoyl, sulfo, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkylsulfanyl, substituted or unsubstituted alkylamino, substituted or unsubstituted alkylcarbonyl, substituted or unsubstituted alkylsulfonyl, substituted or unsubstituted alkylcarbamoyl, substituted or unsubstituted alkylsulfamoyl, substituted or unsubstituted alkylcarbonylamino, substituted or unsubstituted alkylsulfonylamino, substituted or unsubstituted alkyloxycarbonylamino, substituted or unsubstituted aromatic carbocyclyl, substituted or unsubstituted non-aromatic carbocyclyl, substituted or unsubstituted aromatic heterocyclyl, substituted or unsubstituted non-aromatic heterocyclyl, substituted or unsubstituted aromatic carbocyclyloxy, substituted or unsubstituted non-aromatic carbocyclyloxy, substituted or unsubstituted aromatic heterocyclyloxy, substituted or unsubstituted non-aromatic heterocyclyloxy, substituted or unsubstituted aromatic carbocyclylamino, substituted or unsubstituted non-aromatic carbocyclylamino, substituted or unsubstituted aromatic heterocyclylamino, substituted or unsubstituted non-aromatic heterocyclylamino, substituted or unsubstituted aromatic carbocyclylsulfanyl, substituted or unsubstituted non-aromatic carbocyclylsulfanyl, substituted or unsubstituted aromatic heterocyclylsulfanyl, substituted or unsubstituted non-aromatic heterocyclylsulfanyl, substituted or unsubstituted aromatic carbocyclylcarbonyl, substituted or unsubstituted non-aromatic carbocyclylcarbonyl, substituted or unsxdistituted aromatic heterocyclylcarbonyl, substituted or unsubstituted non-aromatic heterocyclylcarbonyl, substituted or unsubstituted aromatic carbocyclylsulfonyl, substituted or unsubstituted non-aromatic carbocyclylsulfonyl, substituted or unsubstituted aromatic heterocyclylsulfonyl, substituted or unsubstituted non-aromatic heterocyclylsulfonyl, substituted or unsubstituted aromatic carbocyclylcarbamoyl, substituted or unsubstituted non-aromatic carbocyclylcarbamoyl, substituted or unsubstituted aromatic heterocyclylcarbamoyl, substituted or unsubstituted non-aromatic heterocyclylcarbamoyl, substituted or unsubstituted aromatic carbocyclylsulfamoyl, substituted or unsubstituted non-aromatic carbocyclylsulfamoyl, substituted or unsubstituted aromatic heterocyclylsulfamoyl, substituted or unsubstituted non-aromatic heterocyclylsulfamoyl, substituted or unsubstituted aromatic carbocyclylcarbonylamino, substituted or unsubstituted non-aromatic carbocyclylcarbonylamino, substituted or unsubstituted aromatic heterocyclylcarbonylamino, substituted or unsubstituted non-aromatic heterocyclylcarbonyl amino, substituted or unsubstituted aromatic carbocyclylsulfonylamino, substituted or unsubstituted non-aromatic carbocyclylsulfonylamino, substituted or unsubstituted aromatic heterocyclylsulfonylamino, or substituted or unsubstituted non-aromatic heterocyclylsulfonylamino, or pharmaceutically acceptable salt thereof. (n-2) The compound of any one of Formula (I) and the above (a) to (m), wherein R.sup.5a is a hydrogen atom, halogen, hydroxy, amino, carbamoyl, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkylamino, substituted or unsubstituted alkylcarbonyl, substituted or unsubstituted alkylcarbamoyl, substituted or unsubstituted alkylcarbonylamino, substituted or unsubstituted alkyloxycarbonylamino, substituted or unsubstituted aromatic carbocyclyl, substituted or unsubstituted non-aromatic carbocyclyl, substituted or unsubstituted aromatic heterocyclyl, substituted or unsubstituted non-aromatic heterocyclyl, substituted or unsubstituted aromatic carbocyclyloxy, substituted or unsubstituted non aromatic carbocyclyloxy, substituted or unsubstituted aromatic heterocyclyloxy, substituted or unsubstituted non-aromatic heterocyclyloxy, substituted or unsubstituted aromatic carbocyclylamino, substituted or unsubstituted non-aromatic carbocyclylamino, substituted or unsubstituted aromatic heterocyclylamino, substituted or unsubstituted non-aromatic heterocyclylamino, substituted or unsubstituted aromatic carbocyclylcarbonyl, substituted or unsubstituted non-aromatic carbocyclylcarbonyl, substituted or unsubstituted aromatic heterocyclylcarbonyl, substituted or unsubstituted non-aromatic heterocyclylcarbonyl, substituted or unsubstituted aromatic carbocyclylcarbamoyl, substituted or unsubstituted non-aromatic carbocyclylcarbamoyl, substituted or unsubstituted aromatic heterocyclylcarbamoyl, substituted or unsubstituted non-aromatic heterocyclylcarbamoyl, substituted or unsubstituted aromatic carbocyclylcarbonylamino, substituted or unsubstituted non-aromatic carbocyclylcarbonylamino, substituted or unsubstituted aromatic heterocyclylcarbonylamino, or substituted or unsubstituted non-aromatic heterocyclylcarbonylamino, or pharmaceutically acceptable salt thereof. (n-8) The compound of any one of Formula (I) and the above (a) to (m), wherein R.sup.5a is a hydrogen atom, halogen, hydroxy, carboxy, amino, carbamoyl, sulfamoyl, sulfo, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkenyloxy, substituted or unsubstituted alkynyloxy, substituted or unsubstituted alkylamino, substituted or unsubstituted alkenylamino, substituted or unsubstituted alkynylamino, substituted or unsubstituted alkylsulfanyl, substituted or unsubstituted alkenylsulfonyl, substituted or unsubstituted alkynylsulfanyl, substituted or unsubstituted alkyloxycarbonyl, substituted or unsubstituted alkenyloxycarbonyl, substituted or unsubstituted alkynyl oxycarbonyl, substituted or unsubstituted alkylcarbamoyl, substituted or unsubstituted alkenylcarbamoyl, substituted or unsubstituted alky ylcarbamoyl, substituted or unsubstituted alkylcarbonylamino, substituted or unsubstituted alkenylcarbonylamino, substituted or unsubstituted alkynylcarbonylamino, substituted or unsubstituted alkyloxycarbonylamino, substituted or unsubstituted alkenyloxycarbonylamino, substituted or unsubstituted alkynyloxycarbonylamino, substituted or unsubstituted aromatic carbocyclyl, substituted or unsubstituted non-aromatic carbocyclyl, substituted or unsubstituted aromatic heterocyclyl, or substituted or unsubstituted non-aromatic heterocyclyl, or pharmaceutically acceptable salt thereof. (n-4) The compound of any one of Formula (I) and the above (a) to (m), wherein R.sup.5a is a hydrogen atom, halogen, hydroxy, carboxy, amino, carbamoyl, sulfamoyl, sulfo, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkylamino, substituted or unsubstituted alkyloxycarbonyl, substituted or unsubstituted alkylcarbamoyl, substituted or unsubstituted alkylcarbonylamino, substituted or unsubstituted alkyloxycarbonylamino, substituted or unsubstituted aromatic carbocyclyl, substituted or unsubstituted non-aromatic carbocyclyl, substituted or unsubstituted aromatic heterocyclyl, or substituted or unsubstituted non-aromatic heterocyclyl, or pharmaceutically acceptable salt thereof. (n-5) The compound of any one of Formula (I) and the above (a) to (m), wherein R.sup.5a is a hydrogen atom, halogen, hydroxy, carboxy, amino, carbamoyl, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkyloxycarbonyl, substituted or unsubstituted alkylcarbamoyl, substituted or unsubstituted alkyloxycarbonylamino, substituted or unsubstituted aromatic carbocyclyl, substituted or unsubstituted non-aromatic carbocyclyl, substituted or unsubstituted aromatic heterocyclyl, or substituted or unsubstituted non-aromatic heterocyclyl, or pharmaceutically acceptable salt thereof. (n-6) The compound of any one of Formula (I) and the above (a) to (m), wherein R.sup.5a is a hydrogen atom, halogen, hydroxy, carboxy, amino, carbamoyl, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkyloxycarbonyl, substituted or unsubstituted alkylcarbamoyl, substituted or unsubstituted alkyloxycarbonylamino, or substituted or unsubstituted aromatic carbocyclyl, or pharmaceutically acceptable salt, thereof. (n-7) The compound of any one of Formula (I) and the above (a) to (m), wherein R.sup.5a is a hydrogen atom; halogen; hydroxy; carboxy; amino; carbamoyl; cyano; alkyl substituted with one or more group(s) selected from halogen, hydroxy, carboxy, carbamoyl, alkylcarbamoyl optionally substituted with one or more group(s) selected from (hydroxy, cyano and alkyloxy), non-aromatic heterocyclylcarbonyl, aromatic carbocyclylcarbamoyl optionally substituted with one or more group(s) selected from (halogen and alkyl), and non-aromatic heterocyclyl carbamoyl; unsubstituted alkyl; alkyloxy substituted with one or more group(s) selected from halogen and an aromatic carbocycle; unsubstituted alkyloxy; unsubstituted alkyloxycarbonyl; alkylcarbamoyl substituted with one or more group(s) selected from halogen, cyano, alkyloxy, alkylcarbonyl, alkylsulfonyl, alkylcarbamoyl, and aromatic carbocyclyl; unsubstituted alkylcarbamoyl; unsubstituted alkyloxycarbonylamino; or unsubstituted aromatic carbocyclyl,
or pharmaceutically acceptable salt thereof. (N-8) The compound of any one of Formula (I) and the above (a) to (m), wherein R.sup.5A is a hydrogen atom; halogen; alkyl substituted with one or more group(s) selected from halogen, hydroxy, carboxy, carbamoyl, alkylcarbamoyl optionally substituted with one or more group(s) selected from (hydroxy, cyano and alkyloxy), non-aromatic heterocyclylcarbonyl, aromatic carbocyclylcarbamoyl optionally substituted with one or more group(s) selected from (halogen and alkyl), and non-aromatic heterocyclyl carbamoyl; unsubstituted alkyl; alkyloxy substituted with one or more group(s) selected from halogen and an aromatic carbocycle; or unsubstituted alkyloxy,
or pharmaceutically acceptable salt, thereof. (n-9) The compound of any one of Formula (I) and the above (a) to (m), wherein R.sup.5a is a hydrogen atom, halogen, amino, carbamoyl, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkylamino, substituted or unsubstituted aromatic carbocyclyl, substituted or unsubstituted non-aromatic carbocyclyl, substituted or unsubstituted aromatic heterocyclyl, or substituted or unsubstituted non-aromatic heterocyclyl, or pharmaceutically acceptable salt thereof. (n-10) The compound of any one of Formula (I) and the above (a) to (m), wherein R.sup.5a is a hydrogen atom, halogen, amino, carbamoyl, cyano, alkyl, haloalkyl, alkyloxy, haloaryloxy, alkylamino, haloalkylamino, substituted or unsubstituted aromatic carbocyclyl, substituted or unsubstituted non-aromatic carbocyclyl, substituted or unsubstituted aromatic heterocyclyl, or substituted or unsubstituted non-aromatic heterocyclyl, or pharmaceutically acceptable salt thereof. (n-11) The compound of any one of Formula (I) and the above (a) to (m), wherein R.sup.5a is a hydrogen atom, halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy, or pharmaceutically acceptable salt thereof. (n-12) The compound of any one of Formula (I) and the above (a) to (m), wherein R.sup.5a is a hydrogen atom, halogen, alkyl, haloalkyl, alkyloxy, or haloalkyloxy, or pharmaceutically acceptable salt thereof. (n-13) The compound of any one of Formula (I) and the above (a) to (m), wherein R.sup.5a is substituted or unsubstituted alkyloxy, or pharmaceutically acceptable salt thereof. (n-14) The compound of any one of Formula (I) and the above (a) to (m), wherein R.sup.5a is alkyloxy or haloalkyloxy, or pharmaceutically acceptable salt thereof. (n-15) The compound of any one of Formula (I) and the above (a) to (m), wherein R.sup.5a is substituted or unsubstituted alkyl, or pharmaceutically acceptable salt thereof. (n-10) The compound of any one of Formula (I) and the above (a) to (m), wherein R.sup.5a is alkyl or haloalkyl, or pharmaceutically acceptable salt thereof. (n-17) The compound of any one of Formula (I) and the above (a) to (m), wherein R.sup.5a is halogen, or pharmaceutically acceptable salt thereof. (n-18) The compound of any one of Formula (I) and the above (a) to (m), wherein R.sup.5a is a fluorine atom or a chlorine atom, or pharmaceutically acceptable salt thereof. (n-19) The compound of any one of Formula (I) and the above (a) to (m), wherein R.sup.5a is a fluorine atom, or pharmaceutically acceptable salt thereof. (o) A compound according to any one of the following (o-1) to (o-9) or a pharmaceutically acceptable salt thereof. (o-1) The compound of any one of Formula (I) and the above (a) to (n), wherein R.sup.5b is a hydrogen atom, carboxy, carbamoyl, sulfamoyl, sulfo, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted alkylcarbonyl, substituted or unsubstituted alkyloxycarbonyl, substituted or unsubstituted alkylcarbamoyl, substituted or unsubstituted aromatic carbocyclyl, substituted or unsubstituted non-aromatic carbocyclyl, substituted or unsubstituted aromatic heterocyclyl, substituted or unsubstituted non-aromatic heterocyclyl, substituted or unsubstituted aromatic carbocyclylcarbonyl, substituted or unsubstituted non-aromatic carbocyclylcarbonyl, substituted or unsubstituted aromatic heterocyclylcarbonyl, substituted or unsubstituted non-aromatic heterocyclylcarbonyl, substituted or unsubstituted aromatic carbocyclylcarbamoyl, substituted or unsubstituted non-aromatic carbocyclylcarbamoyl, substituted or unsubstituted aromatic heterocyclylcarbamoyl, or substituted or unsubstituted non-aromatic heterocyclylcarbamoyl, or pharmaceutically acceptable salt thereof. (o-2) The compound of any one of Formula (I) and the above (a) to (n), wherein R.sup.5b is a hydrogen atom, carboxy, carbamoyl, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted alkylcarbonyl, substituted or unsubstituted alkyloxycarbonyl, substituted or unsubstituted alkylcarbamoyl, substituted or unsubstituted aromatic carbocyclyl, substituted or unsubstituted non-aromatic carbocyclyl, substituted or unsubstituted aromatic heterocyclyl, substituted or unsubstituted non-aromatic heterocyclyl, substituted or unsubstituted aromatic carbocyclylcarbonyl, substituted or unsubstituted non-aromatic carbocyclylcarbonyl, substituted or unsubstituted aromatic heterocyclylcarbonyl, substituted or unsubstituted non-aromatic heterocyclylcarbonyl, substituted or unsubstituted aromatic carbocyclylcarbamoyl, substituted or unsubstituted non-aromatic carbocyclylcarbamoyl, substituted or unsubstituted aromatic heterocyclylcarbamoyl, or substituted or unsubstituted non-aromatic heterocyclylcarbamoyl, or pharmaceutically acceptable salt thereof. (o-3) The compound of any one of Formula (I) and the above (a) to (n), wherein R.sup.5b is a hydrogen atom, carboxy, carbamoyl, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkylcarbonyl, substituted or unsubstituted alkenylcarbonyl, substituted or unsubstituted alkynylcarbonyl, substituted or unsubstituted aromatic carbocyclyl, substituted or unsubstituted non-aromatic carbocyclyl, substituted or unsubstituted aromatic heterocyclyl, or substituted or unsubstituted non-aromatic heterocyclyl, or pharmaceutically acceptable salt thereof. (o-4) The compound of any one of Formula (L) and the above (a) to (n), wherein R.sup.5b is a hydrogen atom, substituted or unsubstituted alkyl, substituted or unsubstituted alkylcarbonyl, substituted or unsubstituted aromatic carbocyclyl, substituted or unsubstituted non-aromatic carbocyclyl, substituted or unsubstituted aromatic heterocyclyl, or substituted or unsubstituted non-aromatic heterocyclyl, or pharmaceutically acceptable salt thereof. (o-5) The compound of any one of Formula (I) and the above (a) to (n), wherein R.sup.5b is a hydrogen atom, or substituted or unsubstituted alkyl, or pharmaceutically acceptable salt thereof. (o-6) The compound of any one of Formula (I) and the above (a) to (n), wherein R.sup.5b is a hydrogen atom, alkyl, or haloalkyl, or pharmaceutically acceptable salt thereof. (o-7) The compound of any one of Formula (I) and the above (a) to (n), wherein R.sup.5b is unsubstituted alkyl, or pharmaceutically acceptable salt thereof. (o-8) The compound of any one of Formula (L) and the above (a) to (n), wherein R.sup.5b is a hydrogen atom; carboxyl carbamoyl; cyano; alkyl substituted with one or more group(s) selected from halogen, hydroxy, carboxy, carbamoyl, alkylcarbamoyl optionally substituted with one or more group(s) selected from (hydroxy, cyano and alkyloxy), non-aromatic heterocyclylcarbonyl, aromatic carbocyclylcarbamoyl optionally substituted with one or more group(s) selected from (halogen and alkyl), and non-aromatic heterocyclylcarbamoyl; unsubstituted alkyl; unsubstituted alkyloxycarbonyl; alkylcarbamoyl substituted with one or more group(s) selected from halogen, cyano, alkyloxy, alkylcarbonyl, alkylsulfonyl, alkylcarbamoyl, and aromatic carbocyclyl; unsubstituted alkylcarbamoyl; or unsubstituted aromatic carbocyclyl,
or pharmaceutically acceptable salt thereof. (o-9) The compound of any one of Formula ft) and the above (a) to (n), wherein R.sup.5b is a hydrogen atom; halogen; alkyl substituted with one or more group (a) selected from halogen, hydroxy, carboxy, carbamoyl, alkylcarbamoyl optionally substituted with one or more group(s) selected from (hydroxy, cyano and alkyloxy), non-aromatic heterocyclylcarbonyl, aromatic carbocyclylcarbamoyl optionally substituted with one or more group(s) selected from (halogen and alkyl), and non-aromatic heterocyclylcarbamoyl;
or unsubstituted alkyl, or pharmaceutically acceptable salt thereof. (p) A compound of any one of the following (p-1) to (p-3) or a pharmaceutically acceptable salt thereof. (p-1) The compound of any one of Formula (I) and the above (a) to (o), wherein n is an integer from 1 to 3, or pharmaceutically acceptable salt thereof. (p-2) The compound of any one of Formula (I) and the above (a) to (o), wherein n is 1 or 2, or pharmaceutically acceptable salt thereof. (p-3) The compound of any one of Formula (I) and the above (a) to (o), wherein n is 1, or pharmaceutically acceptable salt thereof. (q) A compound according to any one of the following (q-1) to (q-7) or a pharmaceutically acceptable salt thereof. (q-1) The compound of any one of Formula (I) and the above (a) to (p), wherein R.sup.2a is a hydrogen atom, halogen, or substituted or unsubstituted alkyl, or R.sup.2a and R.sup.2b which are attached to the same carbon atom are taken together to form oxo, or pharmaceutically acceptable salt thereof. (q-2) The compound of any one of Formula (I) and the above (a) to (p), wherein R.sup.2a is a hydrogen atom, or halogen, or R.sup.2a and R.sup.2b which are attached to the same carbon atom are taken together to form oxo, or pharmaceutically acceptable salt thereof. (q-3) The compound of any one of Formula (I) and the above (a) to (p), wherein R.sup.2a is a hydrogen atom, or R.sup.2a and R.sup.2b which are attached to the same carbon atom are taken together to form oxo, or pharmaceutically acceptable salt thereof. (q-4) The compound of any one of Formula (I) and the above (a) to (p), wherein R.sup.2a is a hydrogen atom, halogen, or substituted or unsubstituted alkyl, or pharmaceutically acceptable salt thereof. (q-5) The compound of any one of Formula (I) and the above (a) to (p), wherein R.sup.2a is a hydrogen atom, halogen, alkyl, or haloalkyl, or pharmaceutically acceptable salt thereof. (q-6) The compound of any one of Formula (I) and the above (a) to (p), wherein R.sup.2a is a hydrogen atom, or halogen, or pharmaceutically acceptable salt thereof. (q-7) The compound of any one of Formula (I) and the above (a) to (p), wherein R.sup.2a is a hydrogen atom, or pharmaceutically acceptable salt thereof. (r) A compound according to any one of the following (r-1) to (r-7) or a pharmaceutically acceptable salt thereof. (r-1) The compound of any one of Formula (I) and the above (a) to (q), wherein R.sup.2b is a hydrogen atom, halogen, or substituted or unsubstituted alkyl, or R.sup.2a and R.sup.2b which are attached to the same carbon atom are taken together to form oxo, or pharmaceutically acceptable salt thereof. (r-2) The compound of any one of Formula (I) and the above (a) to (q), wherein R.sup.2b is a hydrogen atom, or halogen, or R.sup.2a and R.sup.2b which are attached to the same carbon atom are taken together to form oxo, or pharmaceutically acceptable salt thereof. (r-3) The compound of any one of Formula (I) and the above (a) to (q), wherein R.sup.2b is a hydrogen atom, or R.sup.2a and R.sup.2b which are attached to the same carbon atom are taken together to form oxo, or pharmaceutically acceptable salt thereof. (r-4) The compound of any one of Formula (I) and the above (a) to (q), wherein R.sup.2b is a hydrogen atom, halogen, or substituted or unsubstituted alkyl, or pharmaceutically acceptable salt thereof. (r-5) The compound of any one of Formula (I) and the above (a) to (q), wherein R.sup.2b is a hydrogen atom, halogen, alkyl, or haloalkyl, or pharmaceutically acceptable salt, thereof. (r-6) The compound of any one of Formula (I) and the above (a) to (q), wherein R.sup.2b is a hydrogen atom, or halogen, or pharmaceutically acceptable salt thereof. (r-7) The compound of any one of Formula (I) and the above (a) to (q), wherein R.sup.2b is a hydrogen atom, or pharmaceutically acceptable salt thereof. (s) A compound according to any one of the following (s-1) to (s-3) or a pharmaceutically acceptable salt thereof. (s-1) The compound of any one of Formula (I) and the above (a) to (r), wherein m is an integer from 0 to 2, or pharmaceutically acceptable salt thereof. (s-2) The compound of any one of Formula (I) and the above (a) to (r), wherein m is 0 or 1, or pharmaceutically acceptable salt thereof. (a-3) The compound of any one of Formula (I) and the above (a) to (r), wherein m is 0, or pharmaceutically acceptable salt thereof. (t) A compound according to any one of the following (t-1) to (t-4) or a pharmaceutically acceptable salt, thereof. (t-1) The compound of any one of Formula (I) and the above (a) to (s), wherein R.sup.2c is a hydrogen atom, halogen, or substituted or unsubstituted alkyl, or pharmaceutically acceptable salt thereof. (t-2) The compound of any one of Formula (I) and the above (a) to (s), wherein R.sup.2c is a hydrogen atom, halogen, alkyl, or haloalkyl, or pharmaceutically acceptable salt thereof. (t-3) The compound of any one of Formula (I) and the above (a) to (s), wherein R.sup.2c is a hydrogen atom, or halogen, or pharmaceutically acceptable salt thereof. (t-4) The compound of any one of Formula (I) and the above (a) to (s), wherein R.sup.2c is a hydrogen atom, or pharmaceutically acceptable salt thereof. (u) A compound according to any one of the following (u-1) to (u-4) or a pharmaceutically acceptable salt thereof. (u-1) The compound of any one of Formula (I) and the above (a) to (t), wherein R.sup.2d is a hydrogen atom, halogen, or substituted or unsubstituted alkyl, or pharmaceutically acceptable salt thereof. (u-2) The compound of any one of Formula (I) and the above (a) to (t), wherein R.sup.2d is a hydrogen atom, halogen, alkyl, or haloalkyl, or pharmaceutically acceptable salt thereof. (u-3) The compound of any one of Formula (I) and the above (a) to (t), wherein R.sup.2d is a hydrogen atom, or halogen, or pharmaceutically acceptable salt thereof. (u-4) The compound of any one of Formula (I) and the above (a) to (t), wherein R.sup.2d is a hydrogen atom, or pharmaceutically acceptable salt thereof. (v) A compound according to any one of the following (v-1) to (v-4) or a pharmaceutically acceptable salt thereof. (v-1) The compound of any one of Formula (I) and the above (a) to (u), wherein Y.sup.1 is O, or pharmaceutically acceptable salt thereof. (v-2) The compound of any one of Formula (I) and the above (a) to (u), wherein Y.sup.2 is O, or pharmaceutically acceptable salt thereof. (v-3) The compound of any one of Formula (I) and the above (a) to (u), wherein each of Y.sup.1 and Y.sup.2 is O, or pharmaceutically acceptable salt thereof. (v-4) The compound of any one of Formula (I) and the above (a) to (u), wherein Y.sup.1 and Y.sup.2 are each independently O or S, or pharmaceutically acceptable salt, thereof. (w) A compound according to any one of the following (w-1) to (w-4) or a pharmaceutically acceptable salt thereof. (w-1) The compound of any one of Formula (I) and the above (a) to (v), wherein R.sup.4 is a hydrogen atom, halogen, or substituted or unsubstituted alkyl, or pharmaceutically acceptable salt thereof. (w-2) The compound of any one of Formula (I) and the above (a) to (v), wherein R.sup.4 is a hydrogen atom, halogen, alkyl, or haloalkyl, or pharmaceutically acceptable salt thereof. (w-3) The compound of any one of Formula (I) and the above (a) to (v), wherein R.sup.4 is a hydrogen atom, or halogen, or pharmaceutically acceptable salt thereof. (w-4) The compound of any one of Formula (I) and the above (a) to (v), wherein R.sup.4 is a hydrogen atom, or pharmaceutically acceptable salt thereof. (x) A compound according to any one of the following (x-1) to (x-4) or a pharmaceutically acceptable salt thereof. (x-1) The compound of any one of Formula (I) and the above (a) to (w), wherein R.sup.6 is a hydrogen atom, halogen, or substituted or unsubstituted alkyl, or pharmaceutically acceptable salt thereof. (x-2) The compound of any one of Formula (I) and the above (a) to (w), wherein R.sup.6 is a hydrogen atom, halogen, alkyl, or haloalkyl, or pharmaceutically acceptable salt thereof. (x-3) The compound of any one of Formula (I) and the above (a) to (w), wherein R.sup.6 is a hydrogen atom, or halogen, or pharmaceutically acceptable salt thereof. (x-4) The compound of any one of Formula (I) and the above (a) to (w), wherein R.sup.6 is a hydrogen atom, or pharmaceutically acceptable salt thereof. (y) A compound according to any one of the following (y-1) to (y-8) or a pharmaceutically acceptable salt thereof. (y-1) The compound of any one of Formula (I) and the above (a) to (x), wherein R.sup.5a′ is a hydrogen atom, halogen, hydroxy, carboxy, amino, carbamoyl, sulfamoyl, sulfo, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkenyloxy, substituted or unsubstituted alkynyloxy, substituted or unsubstituted alkylamino, substituted or unsubstituted alkenylamino, substituted or unsubstituted alkynylamino, substituted or unsubstituted alkylsulfanyl, substituted or unsubstituted alkenylsulfonyl, substituted or unsubstituted alkynylsulfanyl, substituted or unsubstituted alkyloxycarbonyl, substituted or unsubstituted alkenyloxycarbonyl, substituted or unsubstituted alkynyloxycarbonyl, substituted or unsubstituted alkylcarbamoyl, substituted or unsubstituted alkenylcarbamoyl, substituted or unsubstituted alkynylcarbamoyl, substituted or unsubstituted alkylcarbonylamino, substituted or unsubstituted alkenylcarbonylamino, substituted or unsubstituted alkynylcarbonylamino, substituted or unsubstituted alkyloxycarbonylamino, substituted or unsubstituted alkenyloxycarbonylamino, substituted or unsubstituted alkyloxycarbonylamino, substituted or unsubstituted aromatic carbocyclyl, substituted or unsubstituted non-aromatic carbocyclyl, substituted or unsubstituted aromatic heterocyclyl, or substituted or unsubstituted non-aromatic heterocyclyl, or pharmaceutically acceptable salt thereof. (y-2) The compound of any one of Formula (I) and the above (a) to (x), wherein R.sup.5a′ is a hydrogen atom, halogen, hydroxy, carboxy, amino, carbamoyl, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkyloxycarbonyl, substituted or unsubstituted alkylcarbamoyl, substituted or unsubstituted alkyloxycarbonylamino, substituted or unsubstituted aromatic carbocyclyl, substituted or unsubstituted non-aromatic carbocyclyl, substituted or unsubstituted aromatic heterocyclyl, or substituted or unsubstituted non-aromatic heterocyclyl, or pharmaceutically acceptable salt thereof. (y-3) The compound of any one of Formula (I) and the above (a) to (x), wherein R.sup.5a′ is a hydrogen atom, halogen, amino, carbamoyl, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkylamino, substituted or unsubstituted aromatic carbocyclyl, substituted or unsubstituted non-aromatic carbocyclyl, substituted or unsubstituted aromatic heterocyclyl, or substituted or unsubstituted non-aromatic heterocyclyl, or pharmaceutically acceptable salt thereof. (y-4) The compound of any one of Formula (I) and the above (a) to (x), wherein R.sup.5a′ is a hydrogen atom, halogen, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy, or pharmaceutically acceptable salt thereof. (y-5) The compound of any one of Formula (I) and the above (a) to (x), wherein R.sup.5a′ is a hydrogen atom, halogen, alkyl, haloalkyl, alkyloxy, or haloaryloxy, or pharmaceutically acceptable salt thereof. (y-6) The compound of any one of Formula (I) and the above (a) to (x), wherein R.sup.5a′ is a hydrogen atom, halogen, alkyl, or haloalkyl, or pharmaceutically acceptable salt thereof. (y-7) The compound of any one of Formula (I) and the above (a) to (x), wherein R.sup.5a′ is a hydrogen atom, or halogen, or pharmaceutically acceptable salt thereof. (y-8) The compound of any one of Formula (I) and the above (a) to (x), wherein R.sup.5a′ is a hydrogen atom, or pharmaceutically acceptable salt thereof. (z) A compound according to any one of the following (z-1) to (z-4) or a pharmaceutically acceptable salt thereof. (z-1) The compound of any one of Formula (I) and the above (a) to (y), wherein R.sup.Y is each independently a hydrogen atom, hydroxy, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkenyloxy, substituted or unsubstituted alkynyloxy, substituted or unsubstituted aromatic carbocyclyl, substituted or unsubstituted non-aromatic carbocyclyl, substituted or unsubstituted aromatic heterocyclyl, or substituted or unsubstituted non-aromatic heterocyclyl, or pharmaceutically acceptable salt thereof. (z-2) The compound of any one of Formula (I) and the above (a) to (y), wherein R.sup.Y is each independently a hydrogen atom, hydroxy, cyano, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted alkyloxy, substituted or unsubstituted alkenyloxy, or substituted or unsubstituted alkynyloxy, or pharmaceutically acceptable salt thereof. (z-3) The compound of any one of Formula (I) and the above (a) to (y), wherein R.sup.Y is each independently a hydrogen atom, hydroxy, cyano, substituted or unsubstituted alkyl, or substituted or unsubstituted alkyloxy, or pharmaceutically acceptable salt thereof. (z-4) The compound of any one of Formula (I) and the above (a) to (y), wherein R.sup.Y is each independently a hydrogen atom, hydroxy, cyano, alkyl, haloalkyl, alkyloxy, or haloaryloxy, or pharmaceutically acceptable salt thereof.

(373) The compounds represented by Formula (I) are not limited to specific isomers but include all possible isomers (e.g., keto-enol isomers, imine-enamine isomers, diastereoisomers, enantiomers, rotamers or the like), racemates or mixtures thereof.

(374) For example, a compound represented by Formula (I) wherein R.sup.7a is a hydrogen atom includes the following tautomer.

(375) ##STR00075##

(376) Likewise, a tautomer of the ring represented by the Formula:

(377) ##STR00076##
is included.

(378) In the present specification, in a group represented by the Formula:

(379) ##STR00077##
p1 hydrogen atom(s) which is attached to a ring-constituting atom on Ring B can be replaced with R.sup.10a and R.sup.10c.

(380) In the present specification, in a group represented by the Formula:

(381) ##STR00078##
p2 hydrogen atom(s) which is attached to a ring-constituting atom on Ring C can be replaced with R.sup.10b and R.sup.10d.

(382) In the present, specification, in a group represented by the Formula:

(383) ##STR00079##
p3 hydrogen atom(s) which is attached to a ring-constituting atom on Ring 1) can be replaced with R.sup.10e.

(384) In the present specification, in a group represented by the formula:

(385) ##STR00080##
p1a hydrogen atom(s) which is attached to a ring-constituting atom on Ring B can be replaced with R.sup.11a. Also, any hydrogen atom which is attached to a ring-constituting atom on Ring B can be replaced with R.sup.11c.

(386) In the present specification, in a group represented by the Formula:

(387) ##STR00081##
p2a hydrogen atom(s) which is attached to a ring-constituting atom on Ring C can be replaced with R.sup.11b. Also, any hydrogen atom which is attached to a ring-constituting atom on Ring C can be replaced with R.sup.11a.

(388) In the present specification, in a group represented by the Formula:

(389) ##STR00082##
q1 hydrogen atom(s) which is attached to a ring-constituting atom on Ring E can be replaced with R.sup.12. q2 hydrogen atom(s) which is attached to a ring-constituting atom on Ring E can be replaced with R.sup.13. q3 hydrogen atom(s) which is attached to a ring-constituting atom on Ring F can be replaced with R.sup.14.

(390) In the present specification, in a group represented by the Formula:

(391) ##STR00083##
p1b hydrogen atom(s) which is attached to a ring-constituting atom on Ring B can be replaced with R.sup.10a1.

(392) In the present, specification, in a group represented by the Formula:

(393) ##STR00084##
p1c hydrogen atom(s) which is attached to a ring constituting atom on Ring B can be replaced with R.sup.10a1.

(394) In the present specification, in a group represented by the Formula:

(395) ##STR00085##
p1d hydrogen atom(s) which is attached to a ring-constituting atom on Ring B can be replaced with R.sup.10a2. p2b hydrogen atom(s) which is attached to a ring-constituting atom on Ring C can be replaced with R.sup.10b1.

(396) One or more hydrogen, carbon and/or other atoms in the compounds represented by Formula (I) may be replaced with isotopes of hydrogen, carbon and/or other atoms respectively. Example s of isotopes include hydrogen, carbon, nitrogen, oxygen, phosphorus, sulfur, fluorine, iodine and chlorine, such as .sup.2H, .sup.3H, .sup.11C, .sup.13C, .sup.14C, .sup.15N, .sup.18O, .sup.17O, .sup.31P, .sup.32P, .sup.35S, .sup.18F, .sup.123I and .sup.36Cl respectively. The compounds represented by Formula (I) include the compounds replaced with these isotopes. The compounds replaced with the above isotopes are useful as medicines and include all of radiolabeled compounds of the compound of Formula (I). A “method of radiolabeling” in the manufacture of the “radiolabeled compounds” is encompassed by the present, invention, and the “radiolabeled compounds” are useful for studies on metabolized drug pharmacokinetics, studies on binding assay and/or diagnostic tools.

(397) A radiolabeled compound of the compounds represented by Formula (I) can be prepared using well-known methods in the art. For example, a tritium-labeled compound represented by Formula (I) can be prepared by introducing a tritium to a certain compound represented by Formula (I), through a catalytic dehalogenation reaction using a tritium. This method comprises reacting with an appropriately-halogenated precursor of the compound represented by Formula (I) with tritium gas in the presence of an appropriate catalyst, such as Pd/C, and in the presence or absent of a base. The other appropriate method of preparing a tritium-labeled compound can be referred to “Isotopes in the Physical and Biomedical Sciences, Vol. 1, Labeled Compounds (Part A), Chapter 6 (1987)”. A .sup.14C-labeled compound can be prepared by using a raw material having .sup.14C.

(398) The pharmaceutically acceptable salts of the compounds represented by Formula (D include, for example, salts with alkaline metal (e.g., lithium, sodium, potassium or the like), alkaline earth metal (e.g., calcium, barium or the like), magnesium, transition metal (e.g., zinc, iron or the like), ammonia, organic bases (e.g., trimethylamine, triethylamine, dicyclohexylamine, ethanolamine, diethanolamine, triethanolamine, meglumine, ethylenediamine, pyridine, picoline, quinoline or the like) or amino acids, or salts with inorganic acids (e.g., hydrochloric acid, sulfuric acid, nitric acid, carbonic acid, hydrobromic acid, phosphoric, acid, hydroiodic acid or the like) or organic acids (e.g., formic acid, acetic acid, propionic acid, trifluoroacetic acid, citric acid, lactic acid, tartaric acid, oxalic acid, maleic acid, fumaric acid, mandelic acid, glutaric acid, malic acid, benzoic acid, phthalic acid, ascorbic acid, benzenesulfonic acid, p-toluenesulfonic acid, methanesulfonic acid, ethanesulfonic acid or the like). Especially, salts with hydrochloric acid, sulfuric acid, phosphoric acid, tartaric acid, methanesulfonic acid and the like are included. These salts can be formed by the usual methods.

(399) The compounds represented by Formula (I) of the present invention or pharmaceutically acceptable salts thereof may form solvates (e.g., hydrates or the like) and/or crystal polymorphs. The present invention encompasses those various solvates and crystal polymorphs. “Solvates” may be those wherein any numbers of solvent molecules (e.g., water molecules or the like) are coordinated with the compounds represented by Formula (I). When the compounds represented by Formula (I) or pharmaceutically acceptable salts thereof are allowed to stand in the atmosphere, the compounds may absorb water, resulting in attachment of adsorbed water or formation of hydrates. Recrystallization of the compounds represented by Formula (I) or pharmaceutically acceptable salts thereof may produce crystal polymorphs.

(400) The compounds represented by Formula (I) of the present, invention or pharmaceutically acceptable salts thereof may form prodrugs. The present invention also encompasses such various prodrugs. Prodrugs are derivatives of the compounds of the present invention that have chemically or metabolically degradable groups, and compounds that are converted to the pharmaceutically active compounds of the present invention through solvolysis or under physiological conditions in vivo. Prodrugs include compounds that are converted to the compounds represented by Formula (I) through enzymatic oxidation, reduction, hydrolysis or the like under physiological conditions in vivo, compounds that are converted to the compounds represented by Formula (I) through hydrolysis by gastric acid etc., and the like. Methods for selecting and preparing suitable prodrug derivatives are described in, for example, “Design of Prodrugs, Elsevier. Amsrdam, 1985”. Prodrugs themselves may have some activity.

(401) When the compounds represented by Formula (I) or pharmaceutically acceptable salts thereof have hydroxyl group(s), prodrugs include acyloxy derivatives and sulfonyloxy derivatives that are prepared by, for example, reacting compounds having hydroxyl group(s) with suitable acyl halide, suitable acid anhydride, suitable sulfonyl chlorido, suitable sulfonyl anhydride and mixed anhydride, or with a condensing agent. For example, they include CH.sub.3COO—, C.sub.2H.sub.5COO—, tert-BuCOO—, C.sub.15H.sub.31COO—, PhCOO—, (m-NaOOCPh)COO—, NaOOCCH.sub.2CH.sub.2COO—, CH.sub.3CH(NH.sub.2)COO—, CH.sub.2N(CH.sub.3).sub.2COO—, CH.sub.3SO.sub.3—, CH.sub.3CH.sub.2SO.sub.3—, CF.sub.3SO.sub.3—, CH.sub.2FSO.sub.3—, CF.sub.3CH.sub.2SO.sub.3—, p-CH.sub.3O-PhSO.sub.3—, PhSO.sub.3— and p-CH.sub.3PhSO.sub.3—.

(402) The compounds of the present invention have an antagonistic activity for the P2X7 receptor, and therefore, are useful as a therapeutic and/or preventive agent for diseases associated with the P2X7 receptor. As the diseases associated with the P2X7 receptor, pain, central nervous system diseases, immune diseases and inflammatory diseases and the like, preferably pain are exemplified (Non-patent Document 7-8 and Patent Document 1 etc.).

(403) As pain, pain associated with zoster, postherpetic neuralgia, trigeminal neuralgia, thalamic pain, cancer pain, postoperative pain, menstrual pain, labor pain, chest pain, abdominal pain, colic pain, lumbar backache, headache, migraine, sciatica, sore muscle, orofacial pain, toothache, glossagra, shoulder pain, nociceptive pain, pain associated with deafferentation, psychogenic pain and the like; pain associated with the disease such as entrapment neuropathy, carpal canal syndrome, diabetes, Guillain-Barre syndrome, myofascial pain syndrome, fibromyalgia syndrome, complex regional pain syndrome, causalgia, Hansen's disease, spinal cord injury, stroke, multiple sclerosis, Parkinson's disease, endometriosis, hernia of intervertebral disk, arthritis, rheumatoid arthritis, osteoarthritis, cervical spondylosis deformans, spinal canal stenosis, thoracic outlet syndrome, traumatic brachial plexus injury syndrome, shoulder-hand syndrome, whiplash injury, cholelithiasis, pancreatitis, cystitis, urethritis, urinary calculosis, prostatitis, ulcerative colitis, Crohn's disease, irritable bowel syndrome, bone fracture, osteoporosis, gout, cauda equina syndrome, ankylosing spondylitis, painful spasm, ABC syndrome, skin disease, arteriosclerosis obliterans, Buerger's disease, Raynaud's phenomenon, gangrene, temporomandibular arthrosis, somatoform disorder, somatization disorder, depression and the like;

(404) pain associated with drug therapy, and pain associated with radiation therapy are exemplified.

(405) Additionally, effects for opioid tolerance can be expected.

(406) As central nervous system diseases, Alzheimer's disease, Cerebral amyloid angiopathy, Parkinson's disease, Creutzfeldt-Jakob disease, Huntington's chorea, depression, schizophrenia, attention deficit hyperactivity disorder, sleep disorder, autism spectrum disorder, epilepsy, stroke, multiple sclerosis, spinal cord injury, amyotrophic lateral sclerosis, opioid dependence, cocaine dependence, nicotine dependence and the like are exemplified.

(407) Preferably, as central nervous system diseases, Alzheimer's disease, Cerebral amyloid angiopathy, Parkinson's disease, depression, schizophrenia, attention deficit hyperactivity disorder, sleep disorder, autism spectrum disorder, epilepsy, stroke, multiple sclerosis, spinal cord injury, amyotrophic lateral sclerosis, opioid dependence, cocaine dependence, nicotine dependence and the like are exemplified.

(408) As immune diseases and inflammatory diseases, rheumatoid arthritis, osteoarthritis, asthma, bronchitis, chronic obstructive pulmonary disease, pulmonary emphysema, septic shock, hepatitis, hepatic fibrosis, hepatic cirrhosis, cholecystitis, glomerulonephritis, nephrotic syndrome, pancreatitis, cystitis, urethritis, prostatitis, ulcerative colitis, Crohn's disease, irritable bowel syndrome, psoriasis, atopic dermatitis, contact dermatitis, eczematous dermatitis, delayed-type hypersensitivity reaction, conjunctivitis, uveitis, growth and metastasis of malignant cell (prostate cancer, breast, cancer, lung cancer, uterine cancer, pancreatic cancer, colorectal cancer etc.), leukemia, meningitis, burn injury, glossitis, gingivitis, periodontal disease, esophagitis and the like are exemplified. It is possible that rejection associated with allograft or blood transfusion is involved in the P2X7 receptor. As the other diseases associated with the P2X7 receptor, circulatory diseases such as atherosclerosis, ischemic heart disease, diabetes and the like, bone diseases such as osteoporosis, bone Paget's disease, osteonecrosis, temporomandibular arthrosis and the like, and urologic diseases such as overactive bladder, stress urinary incontinence, prostatomegaly and the like are exemplified.

(409) Preferably, as immune diseases and inflammatory diseases, rheumatoid arthritis, arthritis, osteoarthritis, asthma, bronchitis, chronic obstructive pulmonary disease, cystitis, ulcerative colitis, Crohn's disease and the like are exemplified.

(410) (Synthetic Procedures for the Compound of the Present Invention)

(411) For example, the compounds represented by Formula (I) of the present invention can be prepared by the general procedures described below. The starting materials and reaction reagents used in such synthesis are commercially available or can be synthesized according to methods well known in the art using the compounds commercially available. The methods for extraction, purification and the like may be carried out by using the usual method for the experiments of organic chemistry.

(412) The compounds of the present invention can be synthesized by referring to the known methods in the art.

(413) In all the following steps, when a substituent which interferes with the reaction, e.g. hydroxy, mercapto, amino, formyl, carbonyl, carboxy, is possessed, the substituent is protected by the method such as those described in Protective Groups in Organic Synthesis, Theodora W Greene (John Wiley & Sons) in advance, and the protective group may be removed at a desirable step.

(414) During all the following steps, the order of the steps to be performed may be appropriately changed. In each step, an intermediate may be isolated and then used in the next step.

(415) In this description, meanings of each abbreviation are as follows: DIEA: N,N-diisopropylethylamine DMF: N,N-dimethylformamide DMSO: Dimethyl sulfoxide DPPA: Diphenylphosphoryl azide IPE: Diisopropyl ether NBS: N-bromosuccinimide NMP: N-methylpyrrolidone HATU: O-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate HOAt: 1-hydroxy-7-azabenzotriazole PdCl.sub.2(dppf): [1,1′-bis(diphenylphosphino)ferrocene]palladium (II) dichloride Xantphos: 4,5′-bis(diphenylphosphino)-9,9′-dimethylxanthene
[Method A]

(416) ##STR00086##
wherein G.sup.1, G.sup.2 and G.sup.3 are each independently a leaving group such as halogen, substituted or unsubstituted alkylsulfanyl, substituted or unsubstituted alkylsulfinyl, or substituted or unsubstituted alkylsulfonyl; and the other symbols are the same as the above (1).
Step 1

(417) A compound (A-2) can be synthesized by the reaction of a compound (A-1) with a basic aqueous solution.

(418) As the base, for example, metal hydroxide (e.g., sodium hydroxide, potassium hydroxide, lithium hydroxide etc.), metal carbonate (e.g., sodium carbonate, potassium carbonate, cesium carbonate etc.) and the like are exemplified. 1.0 or more mole equivalent(s), preferably 1.0 to 5.0 mole equivalent(s) can be used per an equivalent of the compound (A-1).

(419) As the reaction solvent, ethers (e.g., tetrahydrofuran, diethyl ether, dioxane, dimethoxyethane etc.), DMF, DMSO, NMP, water and a mixed solvent thereof and the like are exemplified.

(420) The reaction temperature is 0° C. to 40° C., preferably 0° C. to 20° C.

(421) The reaction time is 0.5 to 48 hours, preferably 1 to 16 hours.

(422) The obtained desired compound (A-2) can be purified as necessary by the methods which are usually used (e.g., column chromatography, recrystallization etc.).

(423) Step 2

(424) A compound (A-4) can be synthesized by the reaction of the compound (A-2) with a compound (A-3) in the presence of a base in the appropriate solvent.

(425) In this reaction, 1.0 or more mole equivalent(s) of the compound (A-3), preferably 1.0 to 5.0 mole equivalent(s) can be used per an equivalent of the compound (A-2).

(426) As the base, for example, metal hydroxide (e.g., sodium hydroxide, potassium hydroxide, tripotassium phosphate etc.), metal hydride (e.g., sodium hydride, lithium hydride etc.), metal carbonate (e.g., sodium carbonate, potassium carbonate, cesium carbonate etc.), metal alkoxide (e.g., sodium methoxide, sodium ethoxide, potassium tert-butoxide etc.), metal alkyl (e.g., butyllithium etc.), pyridine, triethylamine. DIEA and the like are exemplified. 1.0 or more mole equivalent(s), preferably 1.0 to 5.0 mole equivalent(s) can be used per an equivalent, of the compound (A-2).

(427) As the reaction solvent, aromatic hydrocarbons (e.g., toluene, benzene, xylene etc.), saturated hydrocarbons (e.g., cyclohexane, hexane etc.), ethers (e.g., tetrahydrofuran, diethyl ether, dioxane, dimethoxyethane etc.), halogenated hydrocarbons (e.g., chloroform, dichloromethane etc.), DMF, DMSO, NMP, acetonitrile, pyridine, water and the like are exemplified. The reaction solvent may be used alone or in combination.

(428) The reaction temperature is 0 to 200° C., under microwave irradiation as necessary, preferably 0 to 150° C.

(429) The reaction time is 0.1 to 72 hours, preferably 0.0 hours to 18 hours.

(430) The obtained desired compound (A-4) can be purified as necessary by the methods which are usually used (e.g., column chromatography, recrystallization etc.).

(431) Step 3

(432) A compound (1α) can be synthesized by the reaction of the compound (A-4) with a compound (A-5) in the presence of a palladium catalyst and a base or an acid without any solvent or in the appropriate solvent as necessary.

(433) In this reaction, 1.0 or more mole equivalent(s) of the compound (A-5), preferably 1.0 to 5.0 mole equivalent(s) can be used per an equivalent of the compound (A-4).

(434) As the base, for example, metal hydroxide (e.g., sodium hydroxide, potassium hydroxide, tripotassium phosphate etc.), metal hydride (e.g., sodium hydride, lithium hydride etc.), metal carbonate (e.g., sodium carbonate, potassium carbonate, cesium carbonate etc.), metal alkoxide (e.g., sodium methoxide, sodium ethoxide, potassium tert-butoxide etc.), metal alkyl (e.g., butyllithium etc.), pyridine, triethylamine, DIEA and the like are exemplified. 1.0 or more mole equivalent(s), preferably 1.0 to 5.0 mole equivalent(s) can be used per an equivalent of the compound (A-4).

(435) As the acid, for example, acetic acid, propionic acid and the like are exemplified. 1.0 or more mole equivalent(s), preferably 1.0 to 5.0 mole equivalent(s) can be used per an equivalent of the compound (A-4).

(436) As the palladium catalyst, palladium acetate, bis(dibenzylideneacetone)palladium, tetrakistriphenylphosphinepalladium, bis(triphenylphosphine)palladium(II) dichloride, bis(tri-tert-butylphosphine)palladium, PdCl.sub.2(dppf) CH.sub.2Cl.sub.2 and the like are exemplified. 0.001 to 0.5 mole equivalents can be used per an equivalent of the compound (A-4).

(437) As the reaction solvent, alcohols (e.g., tert-butanol, isopropanol etc.), aromatic hydrocarbons (e.g., toluene, benzene, xylene etc.), saturated hydrocarbons (e.g., cyclohexane, hexane etc.), ethers (e.g., tetrahydrofuran, diethyl ether, dioxane, dimethoxyethane etc.), halogenated hydrocarbons (e.g., chloroform, dichloromethane etc.), DMF, DMSO, NMP, acetonitrile, pyridine, water and the like are exemplified. The reaction solvent may be used alone or in combination.

(438) The reaction temperature is 0 to 200° C., under microwave irradiation as necessary, preferably 0 to 150° C.

(439) The reaction time is 0.1 to 72 hours, preferably 0.5 hours to 18 hours.

(440) The obtained desired compound (1α) can be purified as necessary by the methods which are usually used (e.g., column chromatography, recrystallization etc.).

(441) [Method B]

(442) ##STR00087##
wherein G.sup.1 and G.sup.3 are the same as the method A, and the other symbols are the same as the above (1).
Step 1

(443) A compound (B-2) can be synthesized by the reaction of a compound (B-1) with the compound (A-3) according to the synthetic procedures described in the step 2 of the method A.

(444) The obtained desired compound (B-2) can be purified as necessary by the methods which are usually used (e.g., column chromatography, recrystallization etc.).

(445) Step 2

(446) A compound (16) can be synthesized by the reaction of the compound (B-2) with the compound (A-5) according to the synthetic procedures described in the step 3 of the method A.

(447) The obtained desired compound (IB) can be purified as necessary by the methods which are usually used (e.g., column chromatography, recrystallization etc.).

(448) [Method C]

(449) ##STR00088##
wherein G.sup.1 and G.sup.3 are the same as the method A, and the other symbols are the same as the above (1).
Step 1

(450) A compound (C-2) can be synthesized by the reaction of a compound (C-1) with the compound (A-3) according to the synthetic procedures described in the step 2 of the method A.

(451) The obtained desired compound (C-2) can be purified as necessary by the methods which are usually used (e.g., column chromatography, recrystallization etc.).

(452) Step 2

(453) A compound (Iy) can be synthesized by the reaction of the compound (C-2) with the compound (A-5) according to the synthetic procedures described in the step 3 of the method A.

(454) The obtained desired compound (Iy) can be purified as necessary by the methods which are usually used (e.g., column chromatography, recrystallization etc.).

(455) [Method D]

(456) ##STR00089##
wherein PG.sup.1 is an appropriate protecting group of a hydroxy group; G.sup.1 and G.sup.3 are the same as the method A, and the other symbols are the same as the above (1).
Step 1

(457) A compound (D-2) can be synthesized by the reaction of a compound (A-1) with a compound (D-1) in the presence of a base in the appropriate solvent.

(458) In this reaction. 1.0 or more mole equivalents) of the compound (D-1), preferably 1.0 to 5.0 mole equivalent(s) can be used per an equivalent of the compound (A-1).

(459) As the base which can be used, for example, metal hydride (e.g., sodium hydrido, lithium hydrido etc.), molal carbonato (e.g., sodium carbonato, potassium bicarbonate, cesium carbonate etc.), metal alkoxide (e.g., sodium methoxide, sodium ethoxide, potassium tert-butoxide etc.), metal alkyl (e.g., butyllithium etc.) are exemplified. 1.0 or more mole equivalents), preferably 1.0 to 1.5 mole equivalents) can be used per an equivalent of the compound (A-1).

(460) As the reaction solvent, alcohols (e.g., tert-butanol, isopropanol etc.), aromatic hydrocarbons (e.g., toluene, benzene, xylene etc.), saturated hydrocarbons (e.g., cyclohexane, hexane etc.), ethers (e.g., tetrahydrofuran, diethyl ether, dioxane, dimethoxyethane etc.), DMF, DMSO, NMP, a mixed solvent thereof and the like are exemplified.

(461) As the reaction temperature, −20° C. to 200° C., preferably 0° C. to 30° C. are exemplified.

(462) As the reaction time, 0.1 to 80 hours, preferably 1 to 16 hours are exemplified.

(463) The obtained desired compound (D-2) can be purified as necessary by the methods which are usually used (e.g., column chromatography, recrystallization etc.).

(464) Step 2

(465) A compound (D-3) can be synthesized by the reaction of the compound (D-2) with the compound (A-5) according to the synthetic procedures described in the step 3 of the method A.

(466) The obtained desired compound (D-3) can be purified as necessary by the methods which are usually used (e.g., column chromatography, recrystallization etc.).

(467) Step 3

(468) A compound (D-4) can be synthesized by the deprotection of the compound (D-3) in the presence of an acid or a Lewis acid or a base in the appropriate solvent.

(469) As the acid, hydrochloric acid-ethyl acetate, hydrochloric acid-methanol, hydrochloric acid-dioxane, hydrobromic acid-acetic acid, hydrobromic acid, sulfuric acid, formic acid, trifluoroacetic acid and the like are exemplified. As the Lewis acid, trimethylsilyl iodide, BBr.sub.3, AlCl.sub.3, BF.sub.3.(Et.sub.2O) and the like are exemplified. As the base, tetrabutyl ammonium fluoride, hydrogen fluoride-pyridine and the like are exemplified. 0.01 or more mole equivalents, preferably 0.5 to 10.0 mole equivalents can be used per an equivalent of the compound (D-3).

(470) As the reaction solvent, alcohols (e.g., methanol, ethanol, isopropanol etc.), aromatic hydrocarbons (e.g., toluene, benzene, xylene etc.), saturated hydrocarbons (e.g., cyclohexane, hexane etc.), ethers (e.g., tetrahydrofuran, diethyl ether, dioxane, dimethoxyethane etc.), halogenated hydrocarbons (e.g., chloroform, dichloromethane etc.), DMF, DMSO, NMP, acetonitrile, DMA, pyridine, water and the like are exemplified. The reaction solvent may be used alone or in combination.

(471) The reaction temperature is 0 to 200° C., under microwave irradiation as necessary, preferably 0 to 150° C.

(472) The reaction time is 0.1 to 72 hours, preferably 0.5 hours to 18 hours.

(473) The obtained desired compound (D-4) can be purified as necessary by the methods which are usually used (e.g., column chromatography, recrystallization etc.).

(474) Step 4

(475) A compound (1α) can be synthesized by the reaction of the compound (D-4) with the compound (A-3) according to the synthetic procedures described in the step 2 of the method B.

(476) The obtained desired compound (1α) can be purified as necessary by the methods which are usually used (e.g., column chromatography, recrystallization etc.).

(477) [Method E]

(478) ##STR00090##
wherein R.sup.A and R.sup.B are each independently hydrogen, or substituted or unsubstituted alkyl, or are taken together to form a substituted or unsubstituted non-aromatic heterocycle) Hal is halogen; PG.sup.1 is an appropriate protecting group of a hydroxy group) G.sup.1 and G.sup.3 are the same as the method A, and the other symbols are the same as the above (1).
Step 1

(479) A compound (E-3) can be synthesized by the reaction of the compound (E-1) with boronic acid or boronate ester (E-2) in the presence of a metal catalyst and a base in the appropriate solvent.

(480) In this reaction, 1.0 or more mole equivalent(s) of boronic acid or boronate ester (E-2), preferably 1.0 to 5.0 mole equivalent(s) can be used per an equivalent of the compound (E-1).

(481) As the metal catalyst, palladium (II) acetate, bis(dibenzylideneacetone)palladium, Tetrakistriphenylphosphinepalladium, bis(triphenylphosphine)palladium (II) dichloride, bis(tri-tert-butylphosphine)palladium, PdCl.sub.2(dppF)CH.sub.2Cl.sub.2 and the like are exemplified. 0.001 to 1.0 mole equivalents) can be used per an equivalent of the compound (E-1).

(482) As the base, lithium hydroxide, sodium hydroxide, potassium hydroxide, potassium tert-butoxide, sodium tert-butoxide, sodium carbonate, cesium carbonate, potassium bicarbonate, sodium hydrogen carbonate, sodium phosphate, sodium hydrogen phosphate, potassium phosphate, potassium hydrogen phosphate and the like can be exemplified. 1.0 to 10.0 mole equivalent(s) can be used per an equivalent of the compound (E-1).

(483) As the reaction solvent, aromatic hydrocarbons (e.g., toluene, benzene, xylene etc.), saturated hydrocarbons (e.g., cyclohexane, hexane etc.), ethers (e.g., tetrahydrofuran, diethyl ether, dioxane, dimethoxyethane etc.). DMF, DMA, NMP, DMSO, water and a mixed solvent thereof and the like are exemplified.

(484) The reaction temperature is 20 to 250° C., under microwave irradiation as necessary, preferably 0 to 200° C.

(485) The reaction time is 0.1 to 48 hours, preferably 0.5 to 12 hours.

(486) The obtained desired compound (E-3) can be purified as necessary by the methods which are usually used (e.g., column chromatography, recrystallization etc.).

(487) Step 2

(488) A compound (E-4) can be synthesized by the reaction of the compound (E-3) with the compound (A-5) according to the synthetic procedures described in the step 2 of the method D.

(489) The obtained desired compound (E-4) can be purified as necessary by the methods which are usually used (e.g., column chromatography, recrystallization etc.).

(490) Step 3

(491) A compound (E-5) can be synthesized by the deprotection of the protecting group of the hydroxy group of the compound (E-4) according to the synthetic procedures described in the step 3 of the method D.

(492) The obtained desired compound (E-5) can be purified as necessary by the methods which are usually used (e.g., column chromatography, recrystallization etc.).

(493) Step 4

(494) A compound (Iα-1) can be synthesized by the reaction of the compound (E-5) with the compound (A-3) according to the synthetic procedures described in the step 2 of the method B.

(495) The obtained desired compound (Iα-1) can be purified as necessary by the methods which are usually used (e.g., column chromatography, recrystallization etc.).

(496) [Method F]

(497) ##STR00091##
wherein each symbol is the same as the above (1).
Step 1

(498) A compound (F-2) can be synthesized by the reaction of the compound (F-1) with 2,2,2,6-tetramethylpiperidino 1-oxyl in the presence of an oxidizing agent.

(499) As the oxidizing agent, for example, sodium hypochlorite, iodobenzene diacetate and the like are exemplified. 1.0 or more mole equivalents), preferably 1.0 to 5.0 mole equivalent(s) can be used per an equivalent of the compound (F-1).

(500) As the reaction solvent, ethers (e.g., tetrahydrofuran, diethyl ether, dioxane, dimethoxyethane etc.), halogenated hydrocarbons (e.g., chloroform, dichloromethane etc.), acetonitrile, water and the like are exemplified. The reaction solvent may be used alone or in combination.

(501) The reaction temperature is 0 to 100° C., preferably 0 to 60° C.

(502) The reaction time is 0.1 to 72 hours, preferably 0.5 hours to 18 hours.

(503) The obtained desired compound (F-2) can be purified as necessary by the methods which are usually used (e.g., column chromatography, recrystallization etc.).

(504) Step 2

(505) A compound (F-1) can be synthesized by the reaction of the compound (F-2) with a compound (F-3) in the presence of a base in the appropriate solvent.

(506) In this reaction, 1.0 or more mole equivalent(s) of the compound (F-3), preferably 1.0 to 5.0 mole equivalent(s) can be used per an equivalent of the compound (F-2).

(507) As the base, for example, metal hydroxide (e.g., sodium hydroxide, potassium hydroxide, tripotassium phosphate etc.), metal hydride (e.g., sodium hydride, lithium hydride etc.), metal carbonato (e.g., sodium carbonato, potassium carbonate, cesium carbonate etc.), metal alkoxide (e.g., sodium methoxide, sodium ethoxide, potassium tert-butoxide etc.), metal alkyl (e.g., butyllithium etc.), pyridine, triethylamine, DIEA and the like are exemplified. 1.0 or more mole equivalent(s), preferably 1.0 to 5.0 mole equivalent(s) can be need per an equivalent of the compound (F-2).

(508) As the reaction solvent, alcohols (e.g., tertbutanol, isopropanol etc.), aromatic hydrocarbons (e.g., toluene, benzene, xylene etc.), saturated hydrocarbons (e.g., cyclohexane, hexane etc.), ethers (e.g., tetrahydrofuran, diethyl ether, dioxane, dimethoxyethane etc.), halogenated hydrocarbons (e.g., chloroform, dichloromethane etc.), DMF, DMSO, NMP, acetonitrile, pyridine, water and the like are exemplified. The reaction solvent may be used alone or in combination.

(509) The reaction temperature is 0 to 200° C., under microwave irradiation as necessary, preferably 0 to 1.50° C.

(510) The reaction time is 0.1 to 72 hours, preferably 0.5 to 18 hours.

(511) The obtained desired compound (F-4) can lie purified as necessary by the methods which are usually used (e.g., column chromatography, recrystallization etc.).

(512) Step 3

(513) A compound (F-5) can be synthesized by the reaction of the compound (F-4) with iodine in a DMSO solution.

(514) The reaction temperature is −10° C. to 200° C., preferably 0° C. to 150° C.

(515) The reaction time is 0.1 to 72 hours, preferably 0.5 hours to 18 hours.

(516) The obtained desired compound (F-5) can be purified as necessary by the methods which are usually used (e.g., column chromatography, recrystallization etc.).

(517) Step 4

(518) A compound (Iα-2) can be synthesized by the reaction of the compound (F-5) with the compound (A-5) according to the synthetic procedures described in the step 3 of the method A.

(519) The obtained desired compound (Iα-2) can be purified os necessary by the methods which are usually used (e.g., column chromatography, recrystallization etc.).

(520) [Method G]

(521) ##STR00092##
wherein R.sup.D and R.sup.E are each independently substituted or unsubstituted alkyl; G.sup.3 is the same as the method A, and the other symbols are the same as the above (1).
Step 1

(522) A compound (G-1) can be synthesized by the reaction of the compound (A-5) with 1-amidinopyrazole hydrochloride.

(523) In this reaction, 1.0 or more mole equivalent(s) of the 1-amidinopyrazole hydrochloride, preferably 1.0 to 5.0 mole equivalent(s) can be used per an equivalent of the compound (A-5).

(524) As the base, for example, metal hydroxide (e.g., sodium hydroxide, potassium hydroxide, tripotassium phosphate etc.), metal hydride (e.g., sodium hydride, lithium hydride etc.), metal carbonate (e.g., sodium carbonate, potassium bicarbonate, cesium carbonate etc.), metal alkoxide (e.g., sodium methoxide, sodium ethoxide, potassium tertbutoxide etc.), metal alkyl (e.g., butyllithium etc.), pyridine, triethylamine, DIEA and the like are exemplified. 1.0 or more mole equivalent(s), preferably 1.0 to 5.0 mole equivalent(s) can be used per an equivalent of the compound (A-5).

(525) As the reaction solvent, aromatic hydrocarbons (e.g., toluene, benzene, xylene etc.), saturated hydrocarbons (e.g., cyclohexane, hexane etc.), ethers (e.g., tetrahydrofuran, diethyl ether, dioxane, dimethoxyethane etc.), halogenated hydrocarbons (e.g., chloroform, dichloromethane etc.), DMF, DMSO, NMP, acetonitrile, DMA and the like are exemplified. The reaction solvent may be used alone or in combination.

(526) The reaction temperature is 0 to 200° C., under microwave irradiation as necessary, preferably 0 to 150° C.

(527) The reaction time is 0.1 to 72 hours, preferably 0.5 to 18 hours.

(528) The obtained desired compound (G-1) can be purified as necessary by the methods which ore usually used (e.g., column chromatography, recrystallization etc.).

(529) Step 2

(530) A compound (G-3) can be synthesized by the reaction of the compound (G-1) with a compound (G-2) in the presence of a base in the appropriate solvent.

(531) In this reaction, 1.0 or more mole equivalent(s) of the compound (G-2), preferably 1.0 to 5.0 mole equivalent(s) can be used per an equivalent of the compound (G-1).

(532) As the base, for example, metal hydroxide (e.g., sodium hydroxide, potassium hydroxide, tripotassium phosphate etc.), metal hydride (e.g., sodium hydride, lithium hydride etc.), metal carbonate (e.g., sodium carbonate, potassium carbonate, cesium carbonate etc.), metal alkoxide (e.g., sodium methoxide, sodium ethoxide, potassium tertbutoxide etc.), metal alkyl (e.g., butyllithium etc.), triethylamine, DIEA, DBU and the like are exemplified. 1.0 or more mole equivalent(s), preferably 1.0 to 5.0 mole equivalent(s) can be used per an equivalent of the compound (G-1).

(533) As the reaction solvent, alcohols (e.g., tertbutanol, isopropanol etc.), aromatic hydrocarbons (e.g., toluene, benzene, xylene etc.), saturated hydrocarbons (e.g., cyclohexane, hexane etc.), ethers (e.g., tetrahydrofuran, diethyl ether, dioxane, dimethoxyethane etc.), DMF, NMP, acetonitrile. DMA and the like are exemplified. The reaction solvent can be used alone or in combination.

(534) The reaction temperature is 0 to 200° C., under microwave irradiation as necessary, preferably 0 to 150° C.

(535) The reaction time is 0.1 to 72 hours, preferably 0.5 hours to 18 hours.

(536) The obtained desired compound (G-3) can be purified as necessary by the methods which are usually used (e.g., column chromatography, recrystallization etc.).

(537) Step 3

(538) A compound (Iγ-1) can be synthesized by the reaction of the compound (G-3) and a compound (A-3) according to the synthetic procedures described in the step 2 of the method A.

(539) The obtained desired compound (Iγ-1) can be purified as necessary by the methods which are usually used (e.g., column chromatography, recrystallization etc.).

(540) The synthesis methods of methods H to N shown below can be used not only in the synthesis of a compound represented by formula (Iα) but also in the synthesis of compounds represented by formula (Iβ) and formula (Iγ).

(541) [Method H]

(542) ##STR00093##
wherein PC.sup.2 is an appropriate protecting group of a hydroxy group; G.sup.1 and G.sup.4 are each independently a leaving group such as halogen, substituted or unsubstituted alkylsulfanyl, substituted or unsubstituted alkylsulfinyl, or substituted or unsubstituted alkylsulfonyl; R.sup.5aa is a hydrogen atom, a hydrogen atom, a substituent selected from the substituent group B, or the like; and the other symbols are the same as the above (1).
Step 1

(543) A compound (H-2) can be synthesized by the deprotection of the protecting grovip of the hydroxy group of the compound (H-1) obtained by the method A according to the synthetic procedures described in the step 3 of the method D.

(544) The obtained desired compound (H-2) can be purified as necessary by the methods which are usually used (e.g., column chromatography, recrystallization etc.).

(545) Step 2

(546) A compound (H-4) can be synthesized by the reaction of the compound (H-2) and a compound (H-3) according to the synthetic procedures described in the step 2 of the method A.

(547) The obtained desired compound (H-4) can be purified as necessary by the methods which are usually used (e.g., column chromatography, recrystallization etc.).

(548) Step 3

(549) A compound represented by a compound (Iα-3) can be synthesized by the reaction of the compound (H-4) and a compound (A-5) according to the synthetic procedures described in the step 3 of the method A.

(550) The obtained desired compound (Iα-3) can be purified as necessary by the methods which are usually used (e.g., column chromatography, recrystallization etc.).

(551) [Method I]

(552) ##STR00094##
wherein R.sup.5ab is substituted or unsubstituted alkyl; and the other symbols are the same as the above (1>.

(553) A compound (Iα-5) can be synthesized by reduction using the compound (Iα-4) obtained by the method A in the appropriate solvent.

(554) As the reducing agent, sodium borohydride, lithium borohydride, lithium aluminum hydride and the like are exemplified. 1 or more mole equivalent(s), preferably 1.0 to 5.0 mole equivalent(s) can be used per an equivalent of the compound (Iα-4).

(555) As the reaction solvent, alcohols (e.g., methanol, ethanol, isopropanol etc.), ethers (e.g., tetrahydrofuran, diethyl ether, dioxane, dimethoxyethane etc.), dichloromethane, water and the like are exemplified. The reaction solvent may be used alone or in combination.

(556) The reaction temperature is −10 to 100° C., preferably 0 to 100° C.

(557) The reaction time is 0.1 to 72 hours, preferably 0.5 hours to 18 hours.

(558) The obtained desired compound (Iα-5) can be purified as necessary by the methods which are usually used (e.g., column chromatography, recrystallization etc.).

(559) [Method J]

(560) ##STR00095##
wherein R.sup.5ab is substituted or unsubstituted alkyl; R.sup.5ac and R.sup.5ad are each independently a hydrogen atom, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aromatic carbocyclyl, substituted or unsubstituted non-aromatic carbocyclyl, substituted or unsubstituted aromatic heterocyclyl, substituted or unsubstituted non-aromatic heterocyclyl or the like; and
the other symbols ore the same as the above (1).
Step 1

(561) A compound (Iα-6) can be synthesized by hydrolysis using the compound (Iα-4) obtained by the method A in the presence of an acid or a base.

(562) As the acid, hydrochloric acid, p-toluenesulfonic acid, sulfuric acid, formic acid, trifluoroacetic acid and the like are exemplified.

(563) As the base, lithium hydroxide, sodium hydroxide, potassium hydroxide, sodium carbonate, cesium carbonate, potassium carbonate, sodium hydrogen carbonate, sodium phosphate, sodium hydrogen phosphate, potassium phosphate, potassium hydrogen phosphato, tetrabutyl ammonium fluoride and the like are exemplified.

(564) 1 or more mole equivalent(s), preferably 5 mole equivalents can be used per an equivalent of the compound (Iα-4).

(565) As the reaction solvent, alcohols (e.g., methanol, ethanol, isopropanol etc.), aromatic hydrocarbons (e.g., toluene, benzene, xylene etc.), saturated hydrocarbons (e.g., cyclohexane, hexane etc.), ethers (e.g., tetrahydrofuran, diethyl ether, dioxane, dimethoxyethane etc.), DMF, DMSO, NMP, acetonitrile. DMA, water and the like are exemplified. The reaction solvent may be used alone or in combination.

(566) The reaction temperature is −10 to 200° C., preferably 0 to 150° C.

(567) The reaction time is 0.1 to 72 hours, preferably 0.5 hours to 18 hours.

(568) The obtained desired compound (Iα-7) can be purified as necessary by the methods which are usually used (e.g., column chromatography, recrystallization etc.).

(569) Step 2

(570) A compound (Iα-7) can be synthesized by the condensation of the compound (Iα-6) with the compound (J-1) in the appropriate solvent.

(571) As the condensing agent, condensing agents such as 1-hydroxybenzotriazole, HOAt, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride, HATU, and (benzotriazol-1-yloxy)tripyrrolidinophosphonium hexafluorophosphate, and bases such as triethylamine and diisopropylethylamine, and the like are exemplified. 1 or more mole equivalent(s), preferably 1 to 5 mole equivalent(s) can be used per an equivalent of the compound (Iα-6).

(572) As the reaction solvent, aromatic hydrocarbons (e.g., toluene, benzene, xylene etc.), saturated hydrocarbons (e.g., cyclohexane, hexane etc.), ethers (e.g., tetrahydrofuran, diethyl ether, dioxane, dimethoxyethane etc.), DMF, NMP, acetonitrile, DMA and the like are exemplified. The reaction solvent can be used alone or in combination.

(573) The reaction temperature is −10 to 200° C., preferably 0 to 150° C.

(574) The reaction time is 0.1 to 72 hours, preferably 0.0 hours to 18 hours.

(575) The obtained desired compound (Iα-7) can be purified as necessary by the methods which are usually used (e.g., column chromatography, recrystallization etc.).

(576) [Method K]

(577) ##STR00096##
wherein Hal is halogen; R.sup.A and R.sup.B are the same as the method E, and the other symbols are the same as the above (1).

(578) A compound (Iα-9) can be synthesized by the reaction of the compound (Iα-8) obtained by the method A with a boronic acid or a boronic acid ester (E-2) according to the synthetic procedures described in the method E.

(579) The obtained desired compound (Iα-9) can bo purified as necessary by the methods which are usually used (e.g., column chromatography, recrystallization etc.).

(580) [Method L]

(581) ##STR00097##
wherein R.sup.5ac is substituted or unsubstituted alkyl, and the other symbols are the same as the above (1).

(582) A compound (Iα-11) can be synthesized by the hydrolysis of the compound (Iα-10) obtained by the method A according to the synthetic procedures described in the step 1 of the method J.

(583) The obtained desired compound (Iα-11) can be purified as necessary by the methods which are usually used (e.g., column chromatography, recrystallization etc.).

(584) [Method M]

(585) ##STR00098##
wherein R.sup.5ac and R.sup.5ad are the same as the method J, and the other symbols are the same as the above (1).

(586) A compound (Iα-12) can be synthesized by the condensation of the compound (Iα-10) obtained by the method K with the compound (J-1) according to the synthetic procedures described in the step 2 of the method J.

(587) The obtained desired compound (Iα-12) can be purified as necessary by the methods which are usually used (e.g., column chromatography, recrystallization etc.).

(588) [Method N]

(589) ##STR00099##
wherein R.sup.5af is substituted or unsubstituted alkyl, substituted or unsubstituted aromatic carbocyclyl, or substituted or unsubstituted aromatic heterocyclyl, and the other symbols are the same as the above (1).

(590) A compound (Iα-13) can be synthesized by the reaction of the compound (Iα-11) obtained by the method K with an alcohol (N-1) in the presence of DPPA in the appropriate solvent.

(591) As the reaction solvent, aromatic hydrocarbons (e.g., toluene, benzene, xylene etc.), saturated hydrocarbons (e.g., cyclohexane, hexane etc.), ethers (e.g., tetrahydrofuran, diethyl ether, dioxane, dimethoxyethane etc.), DMF, DMSO, NMP, acetonitrile, DMA and the like are exemplified. The reaction solvent can be used alone or in combination.

(592) The reaction temperature is −10 to 200° C., preferably 0 to 150° C.

(593) The reaction time is 0.1 to 72 hours, preferably 0.5 hours to 18 hours.

(594) The obtained desired compound (Iα-13) can be purified as necessary by the methods which are usually used (e.g., column chromatography, recrystallization etc.).

(595) In the synthesis of the compound of the present invention, C═O can be appropriately converted to C═S at a desirable step on the basis of the synthesis method of method O shown below. [Method O]

(596) ##STR00100##
wherein each symbol is the same as the above (1).

(597) A compound (Iα′) can be synthesized by the reaction of the compound (Iα) obtained by the method A with 2,4-bis(4-methoxyphenyl)-1,3,2,4-dithiadiphosphethane-2,4-disulfide in the appropriate solvent.

(598) As the reaction solvent, aromatic hydrocarbons (e.g., toluene, benzene, xylene etc.), saturated hydrocarbons (e.g., cyclohexane, hexane etc.), ethers (e.g., tetrahydrofuran, diethyl ether, dioxane, dimethoxyethane etc.), acetonitrile and the like are exemplified. The reaction solvent can be used alone or in combination.

(599) The reaction temperature is −10 to 110° C., preferably 0 to 80° C.

(600) The reaction time is 0.1 to 72 hours, preferably 0.5 hours to 18 hours.

(601) The obtained desired compound (Iα′) can be purified as necessary by the methods which are usually used (e.g., column chromatography, recrystallization etc.).

(602) [Method P]

(603) ##STR00101##
wherein R.sup.5ag is substituted or unsubstituted alkyl, substituted or unsubstituted aromatic carbocyclyl, or substituted or unsubstituted aromatic heterocyclyl, G.sup.1 and G.sup.3 are the same as the method A, and the other symbols are the same as the above (1).
Step 1

(604) A compound (P-2) can be synthesized by the reaction of a compound (P-1) with an acid chloride in the presence of a base in the appropriate solvent.

(605) As the acid chloride, for example, phosphoryl chloride, thionyl chloride, oxalyl chloride and the like are exemplified. 1.0 or more mole equivalent(s), preferably 1.0 to 5.0 mole equivalent(s) can be used per an equivalent of the compound (P-1).

(606) As the base, for example, pyridine, triethylamine, DIEA and the like are exemplified.

(607) As the reaction solvent, aromatic hydrocarbons (e.g., toluene, benzene, xylene etc.), saturated hydrocarbons (e.g., cyclohexane, hexane etc.), ethers (e.g., tetrahydrofuran, diethyl ether, dioxane, dimethoxyethane etc.), halogenated hydrocarbons (e.g., chloroform, dichloromethane etc.) ethers (e.g., tetrahydrofuran, diethyl ether, dioxane, dimethoxyethane etc.), and a mixed solvent thereof and the like are exemplified.

(608) The reaction temperature is 0° C. to 100° C., preferably 0° C. to 20° C.

(609) The reaction time is 0.5 hours to 48 hours, preferably 1 hour to 12 hours.

(610) The obtained desired compound (P-2) can be purified as necessary by the methods which are usually used (e.g., column chromatography, recrystallization etc.).

(611) Step 2

(612) A compound (P-4) can be synthesized by the reaction of the compound (P-2) with a compound (P-3) in the appropriate solvent.

(613) In this reaction, 1.0 or more mole equivalent(s) of the compound (P-3), preferably 1.0 to 3.0 mole equivalent(s) can be used per an equivalent of the compound (P-2).

(614) As the reaction solvent, alcohols (e.g., methanol, ethanol, tert-butanol, isopropanol etc.), aromatic hydrocarbons (e.g., toluene, benzene, xylene etc.), saturated hydrocarbons (e.g., cyclohexane, hexane etc.), ethers (e.g., tetrahydrofuran, diethyl ether, dioxane, dimethoxyethane etc.), DMF, NMP, acetonitrile, DMA and the like are exemplified. The reaction solvent, can be used alone or in combination.

(615) The reaction temperature is 0 to 100° C., preferably 0 to 40° C.

(616) The reaction time is 0.5 to 48 hours, preferably 1 hour to 8 hours.

(617) The obtained desired compound (P-4) can be purified as necessary by the methods which are usually used (e.g., column chromatography, recrystallization etc.).

(618) Step 3

(619) A compound (P-5) can be synthesized by the reaction of the compound (P-4) with a basic aqueous solution according to the synthetic procedures described in the step 1 of the method A.

(620) The obtained desired compound (P-5) can be purified as necessary by the methods which are usually used (e.g., column chromatography, recrystallization etc.).

(621) Step 4

(622) A compound (P-6) can be synthesized by the reaction of the compound (P-5) with the compound (A-3) according to the synthetic procedures described in the step 2 of the method A.

(623) The obtained desired compound (P-6) can be purified as necessary by the methods which are usually used (e.g., column chromatography, recrystallization etc.).

(624) Step 5

(625) A compound (Iα-14) can be synthesized by the reaction of the compound (P-6) with the compound (A-5) according to the synthetic procedures described in the step 3 of the method A.

(626) The obtained desired compound (Iα-14) can be purified as necessary by the methods which are usually used (e.g., column chromatography, recrystallization etc.).

(627) [Method Q]

(628) ##STR00102##
wherein R.sup.F is substituted or unsubstituted alkyl; and the other symbols are the same as the above (1).
Step 1

(629) A compound (Q-3) can be synthesized by the reaction of a compound (Q-1) with a compound (Q-2) in the presence of an acid in the appropriate solvent.

(630) In this reaction, 1.0 or more mole equivalent(s) of the compound (Q-2), preferably 1.0 to 2.0 mole equivalent(s) can be used per an equivalent of the compound (Q-1).

(631) As the acid, for example, acetic acid, trifluoroacetic acid, p-toluenesulfonic acid and the like are exemplified. 0.05 or more mole equivalents, preferably 0.1 to 2.0 mole equivalents can be used per an equivalent of the compound (Q-1).

(632) As the reaction solvent, alcohols (e.g., methanol, ethanol, tert-butanol, isopropanol etc.), aromatic hydrocarbons (e.g., toluene, benzene, xylene etc.), saturated hydrocarbons (e.g., cyclohexane, hexane etc.), ethers (e.g., tetrahydrofuran, diethyl ether, dioxane, dimethoxyethane etc.), DMF, NMP, acetonitrile, DMA and the like are exemplified. The reaction solvent can be used alone or in combination.

(633) The reaction temperature is 0° C. to 100° C., preferably 0° C. to 20° C.

(634) The reaction time is 0.5 hours to 48 hours, preferably 1 hour to 12 hours.

(635) The obtained desired compound (Q-3) can be purified as necessary by the methods which are usually used (e.g., column chromatography, recrystallization etc.).

(636) Step 2

(637) A compound (Q-4) can be synthesized by the reaction of the compound (Q-3) with trimethylsilyl isothiocyanate in the appropriate solvent or without, any solvent.

(638) As the reaction solvent, alcohols (e.g., methanol, ethanol, tort-butanol, isopropanol etc.), aromatic hydrocarbons (e.g., toluene, benzene, xylene etc.), saturated hydrocarbons (e.g., cyclohexane, hexane etc.), ethers (e.g., tetrahydrofuran, diethyl ether, dioxane, dimethoxyethane etc.), DMF, NMP, acetonitrile, DMA and the like are exemplified. The reaction solvent can be used alone or in combination.

(639) The reaction temperature is 0° C. to 200° C., preferably 40° C. to 150° C.

(640) The reaction time is 0.5 hours to 48 hours, preferably 1 hour to 12 hours.

(641) The obtained desired compound (Q-4) can be purified as necessary by the methods which are usually used (e.g., column chromatography, recrystallization etc.).

(642) Step 3

(643) A compound (Q-5) can be synthesized by the reaction of the compound (Q-4) with methyl iodide in the presence of a base in the appropriate solvent.

(644) As the base, for example, metal hydroxide (e.g., sodium hydroxide, potassium hydroxide, tripotassium phosphate etc.), metal hydride (e.g., sodium hydride, lithium hydride etc.), metal carbonate (e.g., sodium carbonate, potassium carbonate, cesium carbonate etc.), metal alkoxide (e.g., sodium methoxide, sodium ethoxide, potassium tert-butoxide etc.), metal alkyl (e.g., butyllithium etc.), pyridine, triethylamine, DIEA and the like are exemplified. 1.0 or more mole equivalent(s), preferably 1.0 to 5.0 mole equivalent(s) can be used per an equivalent of the compound (Q-4).

(645) As the reaction solvent, aromatic hydrocarbons (e.g., toluene, benzene, xylene etc.), saturated hydrocarbons (e.g., cyclohexane, hexane etc.), ethers (e.g., tetrahydrofuran, diethyl ether, dioxane, dimethoxyethane etc.), DMF, NMP, acetonitrile. DMA and the like are exemplified. The reaction solvent can be used alone or in combination.

(646) The reaction temperature is 0° C. to 100° C., preferably 0° C. to 40° C.

(647) The reaction time is 0.5 hours to 48 hours, preferably 1 hour to 8 hours.

(648) The obtained desired compound (Q-5) can be purified as necessary by the methods which are usually used (e.g., column chromatography, recrystallization etc.).

(649) Step 4

(650) A compound (Iα-15) can be synthesized by the reaction of the compound (Q-5) with the compound (A-5) according to the synthetic procedures described in the step 3 of the method A.

(651) The obtained desired compound (Iα-15) can be purified as necessary by the methods which are usually used (e.g., column chromatography, recrystallization etc.).

(652) In the synthesis of the compound of the present invention, C═S can be appropriately converted to C═N(R.sup.Y) at a desirable step on the basis of the synthesis method of method ft shown below.

(653) [Method R]

(654) ##STR00103##
wherein Y.sup.1s is C═N(R.sup.Y), and the other symbols are the same as the above (1).

(655) A compound (Iα″) can be synthesized by the reaction of the compound (Iα′) obtained by the method Q with a compound (R-1) in the presence of an acid or a base in the appropriate solvent.

(656) In this reaction, 1.0 or more mole equivalent(s) of the compound (R-1), preferably 1.0 to 5.0 mole equivalent(s) can be used per an equivalent of the compound (Iα′).

(657) As the acid, for example, acetic acid, trifluoroacetic acid, p-toluenesulfonic acid and the like are exemplified. 0.05 or more mole equivalents, preferably 0.1 to 2.0 mole equivalents can be used per an equivalent of the compound (1α′).

(658) As the base, for example, pyridine, triethylamine, DIEA and the like are exemplified. 1.0 or more mole equivalent(s), preferably 1.0 to 20.0 mole equivalent(s) can be used per an equivalent of the compound (Iα′).

(659) As the reaction solvent, alcohols (e.g., methanol, ethanol, tert-butanol, isopropanol etc.), aromatic hydrocarbons (e.g., toluene, benzene, xylene etc.), saturated hydrocarbons (e.g., cyclohexane, hexane etc.), ethers (e.g., tetrahydrofuran, diethyl ether, dioxane, dimethoxyethane etc.), DMF, NMP, acetonitrile, DMA and the like are exemplified. The reaction solvent can be used alone or in combination.

(660) The reaction temperature is 0 to 150° C., preferably 0 to 80° C.

(661) The reaction time is 0.1 to 72 hours, preferably 0.5 hours to 18 hours.

(662) The obtained desired compound (Iα″) can be purified as necessary by the methods which are usually used (e.g., column chromatography, recrystallization etc.).

(663) An optically active form of the compound represented by Formula (I) can be produced by using an optically active starting material, synthesizing an optically active intermediate by asymmetric synthesis at an appropriate step, or optically resolving racemic intermediates or final products at an appropriate step. The approach for the optical resolution includes a method of resolving optical isomers using an optically active column, kinetic optical resolution using enzymatic reaction or the like, crystallization and resolution of diastereomers by salt formation using a chiral acid or a chiral base, preferential crystallization and the like.

(664) The preferred compound of the present invention not only has an antagonistic activity for the P2X7 receptor but also is useful as a medicine and has any or all of the following superior characteristics: a) The inhibitory activity for CYP enzymes (e.g., CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A4 and the like) is weak. b) The compound demonstrates good pharmacokinetics, such as a high bioavailability, moderate clearance and the like. c) The compound has a high metabolic stability. d) The compound has no irreversible inhibitory effect against CYP enzymes (e.g., CYP3A4) when the concentration is within the range described in the present description as the measurement conditions. e) The compound has no mutagenicity. f) The compound is associated with a low cardiovascular risk. g) The compound has a high solubility. h) The compound has a high selectivity for the P2X7 receptor (e.g., high selectivity in the other receptors of the P2X family). i) The compound has a high brain distribution.

(665) A pharmaceutical composition of the present invention can be administered orally or parenterally. Methods for parenteral administration include dermal, subcutaneous, intravenous, intraarterial, intramuscular, intraperitoneal, transmucosal, inhalation, transnasal, ophthalmic, inner ear or vaginal administration and the like.

(666) In case of oral administration, any forms, which are usually used, such as oral solid formulations (e.g., tablets, powders, granules, capsules, pills, films or the like), oral liquid formulations (e.g., suspension, emulsion, elixir, syrup, lemonade, spirit, aromatic water, extract, decoction, tincture or the like) and the like may prepared according to the usual method and administered. The tablets can be sugar-coated tablets, film-coated tablets, enteric-coating tablets, sustained-release tablets, troche tablets, sublingual tablets, buccal tablets, chewable tablets or orally dispersing tablets. Powders and granules can be dry syrups. Capsules can be soft capsules, micro capsules or sustained-release capsules.

(667) In case of parenteral administration, any forms, which are usually used, such as injections, drips, external preparations (e.g., ophthalmic drops, nasal drops, ear drops, aerosols, inhalations, lotion, infusion, liniment, mouthwash, enema, ointment, plaster, jelly, cream, patch, cataplasm, external powder, suppository or the like) and the like can be preferably administered. Injections can be emulsions whose type is O/W, W/O, O/W/O, W/O/W or the like.

(668) The pharmaceutical composition may be manufactured by mixing an effective amount of the compound of the present invention with various pharmaceutical additives suitable for the formulation, such as excipients, binders, moistening agents, disintegrants, lubricants, diluents and the like. Furthermore, the pharmaceutical composition can be for pediatric patients, geriatric patients, serious cases or operations by appropriately changing the effective amount of the compound of the present invention, formulation and/or various pharmaceutical additives. The pediatric pharmaceutical compositions are preferably administered to patients under 12 or 15 years old. In addition, the pediatric pharmaceutical compositions can be administered to patients who are under 27 days old after the birth, 28 days to 23 months old after the birth, 2 to 11 years old, 12 to 16 years old, or 18 years old. The geriatric pharmaceutical compositions are preferably administered to patients who are 65 years old or over.

(669) Although the dosage of a pharmaceutical composition of the present invention should be determined in consideration of the patient's age and body weight, the type and degree of diseases, the administration route and the like, a usual oral dosage is 0.05 to 100 and preferably 0.1 to 10 mg/kg/day. For parenteral administration, although the dosage highly varies with administration routes, a usual dosage is 0.005 to 10 and preferably 0.01 to 1 mg/kg/day. The dosage may be administered in one to several divisions per day.

(670) The present, invention will be described in more detail with reference to, hut not limited to, the following Examples, Reference Examples and Test Examples.

(671) NMR analysis of each example was performed by 400 MHz using DMSO-d.sub.6, or CDCl.sub.3.

(672) “RT” in tables means retention time in LC/MS: liquid column chromatography/mass analysis and these are measured under the conditions as below:

(673) Condition [1]

(674) Column: Shim-pack XR-ODS (2.2 μm, i.d. 50×3.0 mm) (Shimadzu) Flow rate: 1.6 mL/min UV detection wavelength: 254 nm Mobile phases: [A] is 0.1% formic acid solution, and [B] is 0.1% formic acid in acetonitrile solvent. Gradient: linear gradient of 10% to 100% solvent [B] for 3 minutes was performed, and 100% solvent [B] was maintained for 0.5 minute.
Condition [2] Column: ACQUITY HPLC (registered trademark BEH C18 (1.7 μm i.d.2.1×50 mm)(Waters) Flow rate: 0.8 mL/min UV detection wavelength: 254 nm Mobile phases: [A] is 10 mmol/L Ammonium Carbonate solution, and [B] is acetonitrile. Gradient: linear gradient of 5% to 100% solvent [B] for 3.5 minutes was performed, and 100% solvent [B] was maintained for 0.5 minute.
Condition [3] Column: ACQUITY UPLC (registered trademark) BEH C18 (1.7 μm i.d. 2.1×50 mm)(Waters) Flow rate: 0.8 mL/min UV detection wavelength: 254 nm Mobile phases: [A] is 0.1% formic acid solution, and [B] is 0.1% formic acid in acetonitrile solvent. Gradient: linear gradient of 5% to 100% solvent [B] for 3.5 minutes was performed, and 100% solvent [B] was maintained for 0.5 minute.

(675) In the structural formulas of the compounds described in Examples, the following bonding pattern means a double bond and represents that stereoscopic information on E-Z conformation is unknown. A compound having the bond represented by the following bonding pattern is only an E form, only a Z form, or a mixture of an E form and a Z form.

(676) ##STR00104##

Example 1

Synthesis of Compound I-0001

(677) ##STR00105##
Step 1

(678) Under nitrogen atmosphere, 2-(trimethylsilyl)ethanol (6.04 mL, 41.9 mmol) was dissolved in tetrahydrofuran (100 mL). Under ice cooling, sodium hydride (60% oil dispersion, 1.23 g, 30.7 mmol) was added to the solution. The mixture was stirred at room temperature for 30 minutes. Under ice cooling, the compound I (5.0 g, 27.9 mmol) in 50 mL of tetrahydrofuran solution was added dropwise to the mixture. The mixture was stirred at room temperature for 3 hours. 1 mol/L aqueous solution of hydrochloric acid was added to the mixture. The mixture was extracted with ethyl acetate. The organic layer was washed by the saturated aqueous solution of sodium hydrogen carbonate and brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by silica-gel column chromatography (hexane-ethyl acetate) to give the compound 2 (6.24 g, yield 85.7%).

(679) .sup.1H-NMR (CDCl.sup.3) δ: 0.09 (s, 9H), 1.20 (t, J=8.0 Hz, 2H), 3.91 (s, 3H), 4.54 (t, J=8.0 Hz, 2H), 7.86 (s, 1H).

(680) Step 2

(681) The compound 2 (1.0 g, 3.83 mmol) was dissolved in dioxane (10 mL). 3-chloro-2-methylaniline (760 mg, 5.37 mmol), bis(dibenzylideneacetone)palladium (220 mg, 0.383 mmol), Xantphos (333 mg, 0.575 mmol) and cesium carbonate (1.75 g, 5.37 mmol) were added to the solution. The mixture was stirred under reflux for 8 hours. Water was added to the mixture. The mixture was extracted with ethyl acetate. The organic layer was washed by brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by silica-gel column chromatography (hexane-ethyl acetate) to give the compound 3 (1.1.5 g, yield 82.0%).

(682) .sup.1H-NMR (CDCl.sub.3) δ: 0.07 (s, 9H), 1.19 (t, J=8.1 Hz, 2H), 2.38 (s, 3H), 3.84 (e, 3H), 4.47 (t, J=8.4 Hz, 2H), 6.58 (s, 1H), 7.08-7.10 (m, 2H), 7.79 (s, 1H), 7.87-7.95 (m, 1H).

(683) Step 3

(684) The compound 3 (1.14 g, 3.12 mmol) was dissolved in tetrahydrofuran (5 mL). Tetrabutyl ammonium fluoride (1 mol/L tetrahydrofuran solution. 6.2 mL, 6.2 mmol) was added to the solution. The mixture was stirred at room temperature for 3 days. The solvent was evaporated under reduced pressure. The obtained residue was purified by silica-gel column chromatography (chloroform-methanol) to give the compound 4 (828 mg, yield 100%).

(685) .sup.1H-NMR (DMSO-d.sub.6) δ: 2.25 (s, 3H), 3.64 (s, 3H), 7.13-7.40 (m, 3H), 7.67-7.82 (m, 1H), 7.90-8.11 (br, 1H), 11.20-11.06 (br, 1H).

(686) Step 4

(687) Under nitrogen atmosphere), the compound 4 (53 mg, 0.199 mmol) was dissolved in a mixed solution of DMF (0.3 mL) and dimethoxyethane (1.5 mL). Sodium hydride (60% oil dispersion, 9 mg, 0.225 mmol) was added to the solution. The mixture was stirred at room temperature for 5 minutes. Then, lithium bromide (35 mg, 0.403 mmol) was added to the mixture. The mixture was stirred for 10 minutes, p-Fluorobenzyl bromide (50 μL, 0.402 mmol) was added to the mixture. The mixture was stirred at room temperature for 2 days. A 2 mol/L aqueous solution of hydrochloric acid was added to the mixture. The mixture was extracted with ethyl acetate. The organic layer was washed by water, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by silica-gel column chromatography (chloroform-methanol) to give the compound I-0001 (12 mg, yield 16.0%).

(688) .sup.1H-NMR (CDCl.sub.3) δ: 2.06 (s, 3H), 3.71 (s, 3H), 5.01 (s, 2H), 6.66 (d, J=6.4 Hz, 1H), 6.80 (s, 1H), 7.04-7.15 (m, 4H), 7.32-7.40 (m, 2H), 7.63-7.61 (br, 1-H).

Example 2

Synthesis of Compound I-0002

(689) ##STR00106##
Step 1

(690) The compound I (40.0 g, 223 mmol) was dissolved in tetrahydrofuran (80 mL). A 1 mol/L aqueous solution of sodium hydroxide (447 mL, 447 mmol) was added to the solution. The mixture was stirred at room temperature for 4 hours. The reaction mixture was washed by ethyl ether. A 2 mol/L hydrochloric acid solution (230 mL, 400 mmol) was added to the aqueous layer. The mixture was stirred. The precipitates were filtered, washed by water, and dried to give the compound 5<30.8 g. yield 86%).

(691) .sup.1H-NMR (DMSO-d.sub.6) δ: 3.70 (s, 3H), 7.60 (s, 1H)

(692) Step 2

(693) The compound 5 (2.0 g, 12.46 mmol) was dissolved in dichloromethane (20 mL). DIEA (3.26 mL, 18.68 mmol) was added to the solution. The mixture was stirred until dissolved. Then, 3,5-difluorobenzyl bromide (1.91 mL, 14.95 mmol) was added to the mixture. The mixture was stirred at room temperature for 4 hours. After the mixture was left standing overnight, the precipited solids wore filtered, and dried to give the compound 6 (1.1 g, yield 31%).

(694) .sup.1H NMR (DMSO-d.sub.6) δ: 3.70 (s, 3H), 5.30 (s, 2H), 7.05-7.13 (m, 2H), 7.82 (m, 1H)

(695) Step 3

(696) The compound 6 (100 mg, 0.35 mmol) was dissolved in dioxane (2 mL). 3-chloro-2-methylaniline (74 mg, 0.52 mmol) was added to the solution. The mixture was stirred under microwave irradiation at 170° C. for 10 minutes. The solvent in the reaction mixture was evaporated under reduced pressure. The obtained residue was purified by silica-gel column chromatography (ethyl acetate-n-hexane) to give the compound I-0002 (33 mg, yield 24%).

(697) .sup.1H-NMR (CDCl.sub.3) δ: 2.05 (s, 3H), 3.73 (s, 3H), 5.01 (s, 2H), 6.65 (m, 1H), 6.75-6.95 (m, 4H), 7.05-7.15 (m, 2H), 7.59 (s, 1H)

Example 3

Synthesis of Compound I-0003

(698) ##STR00107##
Step 1

(699) The compound 7 (5 g, 41.6 mmol) was dissolved in concentrated sulfuric acid (35 mL). Under ice cooling, potassium nitrate (3.82 g, 37.8 mmol) dissolved in sulfuric acid (8 mL) was added to the solution. The mixture was stirred for 80 minutes. Water and ice were added to the reaction mixture. The precipited solids were filtered to give the compound 8 (5.68 g, yield 00%).

(700) .sup.1H-NMR (CDCl.sub.3) δ: 5.18 (s, 4H), 7.89 (d, J=8.2 Hz, 1H), 8.11 (s, 1H), 8.18 (dd, J=8.3, 1.8 Hz, 1H).

(701) Step 2

(702) The compound 8 (5.63 g, 34.1 mmol) was dissolved in ethanol (56 mL). Tin chloride dihydrate (23.1 g, 102 mmol) was added to the solution. The mixture was stirred at 70° C. for 1 hour. After cooled to room temperature, water and 2 mol/L aqueous solution of sodium hydroxide were added to the reaction mixture to adjust the pH to 7. The reaction mixture was extracted with ethyl acetate. The organic layer was washed by brine. The solvent was evaporated under reduced pressure to give the crude product of the compound 9 (4.6 g, yield 98%).

(703) .sup.1H-NMR (CDCl.sub.3) δ: 8.71 (br s, 2H), 6.02 (s, 4H), 6.57 (s, 1H), 6.60 (dd, J=7.9, 2.0 Hz, 1H), 7.01 (d, J=7.9 Hz, 1H).

(704) Step 3

(705) The compound 9 (7.5 g, 27.7 mmol) was dissolved in acetonitrile (90 mL). NBS (5.18 g, 29.1 mmol) was added to the solution at −10° C. The mixture was stirred at −10° C. for 30 minutes. Water was added to the reaction mixture. The mixture was extracted with ethyl acetate. The organic layer was washed by water and brine. The solvent was evaporated under reduced pressure. The obtained residue was purified by silica-gel column chromatography (hexane-ethyl acetate) to give the mixture 10 (5:1 mixture of the compound 10-a and the compound 10-b) (3.68 g, yield 62%).

(706) .sup.1H-NMR (CDCl.sub.3) δ: 4.08 (s, 2H), 4.98 (dd, J=7.8, 1.3 Hz, 4H), 6.61 (s, 1H), 7.28 (s, 1H).

(707) Step 4

(708) The mixture 10 (3.68 g, 17.2 mmol) was dissolved in dioxane (86 mL) and water (7.2 mL). Trimethylboroxine (2.88 mL, 20.6 mmol), PdCl.sub.2 (dppf) CH.sub.2Cl.sub.2 (1.40 g, 1.72 mmol) and potassium carbonate (7.13 g, 51.6 mmol) were added to the solution. The mixture was stirred under reflux for 3 hours. Water was added to the reaction mixture. The mixture was extracted with ethyl acetate. The organic layer was washed by water and brine. The solvent was evaporated under reduced pressure. The obtained residue was purified by silica-gel column chromatography (hexane-ethyl acetate). The obtained residue was solidified with ethyl acetate. The precipitated solids were filtered to afford the compound 11 (694 mg, yield 27%).

(709) .sup.1H-NMR (CDCl.sub.3) δ: 2.18 (s, 3H), 3.62 (s, 2H), 5.01 (s, 4H), 6.56 (s, 1H), 6.92 (s, 1H).

(710) Step 5

(711) The compound 11 (122 mg, 0.82 mmol) was dissolved in dioxane (4 mL). The compound 6 (21.3 mg, 0.74 mmol) was added to the solution. The mixture was stirred under microwave irradiation at 150° C. for 10 minutes. Water was added to the reaction mixture. The mixture was extracted with ethyl acetate. The organic layer was washed by brine. The solvent, was evaporated. The obtained residue was purified by amino column chromatography (chloroform-methanol) to give the compound I-0003 (17 mg, yield 5%).

(712) .sup.1H-NMR (DMSO.Math.D.sub.6) δ: 3.59 (s, 3H), 4.94 (s, 4H), 5.20 (s, 2H), 7.01-7.03 (m, 3H), 7.11 (s, 1H), 7.24 (t, J=9.0 Hz, 1H), 7.34 (s, 1H), 8.36 (s, 1H).

Example 4

Synthesis of Compound I-0004

(713) ##STR00108##
Step 1

(714) The compound 5 (0.5 g, 8.11 mmol) was dissolved in dichloromethane (5 mL). DIEA (0.82 mL, 4.67 mmol) was added to the solution. The mixture was stirred until dissolved. Then, 3,4,5-trifluorobenzyl bromide (0.50 mL, 1.67 mmol) was added to the mixture. The mixture was stirred al room temperature for 1 hour. After the mixture was left standing overnight, the precipitated solids were filtered, and dried to give, the compound 12 (0.2 g, yield 22%).

(715) .sup.1H-NMR (DMSO-d.sub.6) δ: 3.70 (s, 3H), 5.26 (s, 2H), 7.33-7.43 (m, 2H), 7.79 (s, 1H)

(716) Step 2

(717) The compound 12 (100 mg, 0.35 mmol) was dissolved in dioxane (2 mL). 3-chloro-2-methylaniline (70 mg, 0.49 mmol) was added to the solution. The mixture was stirred under microwave irradiation at 170° C. for 10 minutes. The solvent was evaporated under reduced pressure. The obtained residue was purified by silica-gel column chromatography (ethyl acetate-n-hexane, subsequently chloroform-methanol-water) to give the compound I-0004 (47 mg, yield 35%).

(718) .sup.1H-NMR (DMSO-d.sub.6) δ: 1.90 (s, 3H), 3.61 (s, 3H), 5.14 (brs, 2H), 6.90-7.60 (m, 7H)

Example 5

Synthesis of Compound I-0005

(719) ##STR00109##

(720) The compound 5 (5 g, 31.1 mmol) was dissolved in dichloromethane (50 mL). DIEA (8.2 mL, 40.7 mmol) was added to the solution. The mixture was stirred until dissolved. Then, 3-chloro-4-fluorobenzyl bromide (5.03 mL, 37.4 mmol) was added to the mixture. The mixture was stirred at room temperature for 8 hours. After the mixture was left standing overnight, the precipitated solids were filtered, and dried to give the compound 13 (3.0 g, yield 32%).

(721) .sup.1H-NMR (DMSO-d.sub.6) δ: 3.70 (s, 3H), 5.29 (s, 2H), 7.32-7.38 (m, 1H), 7.46 (t, 1H, J=8.9 Hz), 7.64 (1H, dd, J=7.0, 1.9 Hz), 7.84 (1H, s)

(722) Step 2

(723) The compound 13 (250 mg, 0.83 mmol) was dissolved in dioxane (4 mL). The compound 14 (191 mg, 1.07 mmol) was added to the solution. The mixture was stirred under microwave irradiation at 150° C. for 20 minutes. Water was added to the reaction mixture. The mixture was extracted with ethyl acetate. The organic layer was washed by brine. The solvent was evaporated under reduced pressure. The obtained residue was purified by silica-gel column chromatography (chloroform-methanol) to give the compound I-0005 (194 mg, yield 53%).

(724) .sup.1H-NMR (DMSO-D.sub.6) δ: 1.95<s, 3H), 2.77 (s, 3H), 3.60 (s, 5H), 5.20 (s, 2H), 7.37 (s, 3H), 7.48 (s, 1H), 7.58 (s, 1H), 7.74 (s, 1H), 8.49 (s, 1H).

Example 6

Synthesis of Compound I-0006

(725) ##STR00110##

(726) The compound 13 (100 mg, 0.330 mmol) was dissolved in dioxane (2.0 mL). 4-Chloro-2,5-dimethylaniline (103 mg, 0.660 mmol) was added to the solution. The mixture was stirred under microwave irradiation at 130° C. for 10 minutes. The solvent was evaporated under reduced pressure. The obtained residue was purified by reverse-phase silica-gel column chromatography (water-acetonitrile) to give the compound I-0006 (61.6 mg, yield 44%) as a white powder.

(727) LC-MS (Condition [3]): RT=2.07, 422 [M+H]

(728) 1H-NMR (DMSO-D6) δ: 1.79 (3H, s), 2.26 (3H, s), 3.60 (3H, s), 5.17 (2H, br s), 6.95-7.55 (6H, m), 8.38 (1H, s).

Example 7

Synthesis of Compound I-0007

(729) ##STR00111##
Step 1

(730) The compound 5 (10 g, 62.3 mmol) was dissolved in dichloromethane (100 mL). DIEA (16.32 mL, 93 mmol) was added to the solution. The mixture was stirred until dissolved. Then, benzyl bromide (8.89 mL, 74.7 mmol) was added to the mixture. The mixture was stirred at room temperature for 3 hours. After the mixture was left, standing overnight, 2 mol/L aqueous solution of hydrochloric acid was added to the reaction mixture. The mixture was extracted with chloroform. The organic layer was washed by the saturated aqueous solution of sodium hydrogen carbonate and brine, and dried over anhydrous sodium sulfate. The obtained residue was solidified with ethyl acetate. The precipitated solids were filtered, and dried to give the compound 15 (8.42 g, yield 54%).

(731) .sup.1H-NMR (DMSO-D.sub.6) δ: 1.95 (s, 3H), 2.77 (s, 8H), 3.60 (s, 5H), 5.20 (s, 2H), 7.37 (s, 3H), 7.48 (s, 1H), 7.58 (s, 1H), 7.74 (s, 1H), 8.49 (s, 1H).

(732) Step 2

(733) Under nitrogen atmosphere, the compound 2 (80 mg, 0.319 mmol) was dissolved in dioxane (1.6 mL). 2-methyl-3-methoxyaniline (52.5 mg, 0.383 mmol), palladium acetate (2.85 mg, 0.013 mmol), Xantphos (11.04 mg, 0.019 mmol) and cesium carbonate (104 mg, 0.318 mmol) were added to the solution. The mixture was stirred under reflux for 5 hours. Water was added to the reaction mixture. The mixture was extracted with dichloromethane. The organic layer was washed by the saturated aqueous solution of ammonium chloride and brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by silica-gel column chromatography (chloroform-methanol) to give the compound I-0007 (12.5 mg, yield 11%).

(734) LC-MS (Condition (31): RT=1.53, 352 [M+H].sup.+

(735) .sup.1H-NMR (DMSO-D.sub.6) δ: 1.67 (s, 3H), 3.62 (s, 3H), 3.74 (s, 3H), 5.21 (s, 2H), 6.68 (1H, d, d=7.8 Hz), 6.84 (1H, d, J=8.3 Hz), 7.33-7.44 (m, 7H), 8.37 (s, 1H).

Example 8

Synthesis of Compound I-0008

(736) ##STR00112##
Step 1

(737) The compound 5 (300 mg, 1.87 mmol) was dissolved in dichloromethane (3 mL). DIEA (0.359 mL, 2.06 mmol) was added to the solution. The mixture was stirred until dissolved. Then, 2-bromoethylbenzene (380 mg, 2.06 mmol) was added to the mixture. The mixture was stirred at room temperature for 1.5 hours. After the mixture was left standing overnight, the reaction mixture was poured into water. The mixture was extracted with ethyl acetate. The organic layer was washed by brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by silica-gel column chromatography (methanol-chloroform) to give the compound 16 (15.3 mg, yield 3%).

(738) .sup.1H-NMR (CDCl3) δ: 3.11 (t, 2H), 3.19 (s, 3H), 4.25 (t, 2H), 6.36 (s, 1H), 7.12-7.14 (m, 2H), 7.28-7.35 (m, 3H)

(739) Step 2

(740) The compound 2 (1.5.0 mg, 0.057 mmol) was dissolved in dioxane (0.75 mL). 3-Chloro-2-methylaniline (16.0 mg, 0.113 mmol) was added to the solution. The mixture was stirred under microwave irradiation at 130° C. for 10 minutes. The solvent was evaporated under reduced pressure. The obtained residue was purified by silica-gel column chromatography (ethyl acetate-n-hexane) to give the compound I-0008 (13.1 mg, yield 63%).

(741) .sup.1H-NMR (CDCl3) δ; 3.12 (t, 2H), 2.22 (s, 3H), 3.48 (s, 3H), 4.07 (t, 2H), 6.30 (s, 1H), 6.67-6.69 (d, 2H), 7.09-7.12 (m, 2H), 7.21-7.23 (m, 2H), 7.26-7.28 (m, 1H), 7.28-7.36 (m, 2H), 7.53 (m, 1H)

Example 9

Synthesis of Compound I-0009

(742) ##STR00113##
Step 1

(743) The compound 17 (500 mg, 3.52 mmol) was dissolved in dichloromethane (5 mL). DIEA (921 μL, 5.28 mmol) and benzyl bromide (501 μL, 4.22 mmol) were added to the solution. The mixture was stirred at room temperature for 1 day. A 2 mol/L aqueous solution of hydrochloric acid was added to the mixture. The mixture was extracted with ethyl acetate. The organic layer was washed by brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by silica-gel column chromatography (chloroform-methanol) to give the compound 18 (567 mg, yield (>9.4%).

(744) .sup.1H-NMR (CDCl.sub.3) δ: 2.60 (s, 3H), 5.03 (s, 2H), 6.07 (d, J=7.6 Hz, 1H), 7.16-7.29 (m, 3H), 7.35-7.49 (m, 3H).

(745) Step 2

(746) The compound 18 (0.100 mg, 0.430 mmol) was dissolved in tert-butanol (2 mL). Acetic acid (369 μL, 6.46 mmol) and 3-chloro-2-methylaniline (91 mg, 0.646 mmol) were added to the solution. The mixture was stirred under reflux for 33 hours. After cooled to room temperature, the mixture was diluted with ethyl acetate. The mixture was washed by the saturated aqueous solution of sodium hydrogen carbonate and brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by silica-gel column chromatography (hexane-ethyl acetate) to give the compound I-0009 (65 mg, yield 46.3%).

(747) .sup.1H NMR (CDCl.sub.3) δ: 2.03 (s, 3H), 5.07 (s, 2H), 5.43 (d, J=7.6 Hz, 1H), 6.68 (d, J=6.81 Hz, 1H), 7.05-7.13 (m, 2H), 7.20 (d, J=7.6 Hz, 1H), 7.32-7.49 (m, 6H).

Example 10

Synthesis of Compound I-0010

(748) ##STR00114##
Step 1

(749) The compound 19 (5.0 g, 29.9 mmol) was dissolved in tetrahydrofuran (10 mL). A 1 mol/L aqueous solution of sodium hydroxide (45 mL. 45.0 mmol) was added to the solution. The mixture was stirred at room temperature for 24 hours. The reaction mixture was washed by diethyl ether. Under ice cooling, 2 mol/L aqueous solution of hydrochloric acid was added to the mixture to adjust the pH to 3. The precipitated solids were filtered, and washed by cold water. The obtained solid was dried to give the compound 20 (2.5 g, yield 56.2%).

(750) .sup.1H-NMR (DMSO-d.sub.6) δ: 8.15 (s, 1H).

(751) Step 2

(752) The compound 20 (500 mg, 3.37 mmol) was dissolved in dichloromethane (5 mL). DIEA (882 μL, 5.05 mmol) and benzyl bromide (480 μL, 4.04 mmol) were added to the solution. The mixture was stirred al room temperature for 2 days. A 2 mol/L aqueous solution of hydrochloric acid was added to the mixture. The mixture was extracted with ethyl acetate. The organic layer was washed by brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by silica-gel column chromatography (chloroform-methanol) to afford the compound 21 (331 mg, yield 41.2%).

(753) .sup.1H-NMR (CDCl.sub.3) δ: 5.22 (s, 2H), 7.22-7.30 (m, 2H), 7.38-7.50 (m, 3H).

(754) Step 3

(755) The compound 21 (100 mg, 0.419 mmol) was dissolved in dioxane (3 mL). 3-Chloro-2-methylaniline (71 mg, 0.501 mmol), palladium acetate (9 mg, 0.04 mmol), Xantphos (36 mg, 0.062 mmol) and cesium carbonate (191 mg, 0.587 mmol) were added to the solution. The mixture was stirred under microwave irradiation at 1.30° C. for 90 minutes. Water was added to the reaction mixture. The mixture was extracted with ethyl acetate. The organic layer was washed by brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by silica-gel column chromatography (chloroform-methanol) to give the compound I-0010 (15 mg, yield 10.4%).

(756) .sup.1H-NMR (CDCl.sub.3) δ: 2.06 (s, 3H), 5.04 (s, 2H), 6.67 (d, J=6.8 Hz, 1H), 7.06-7.65 (m, 911).

Example 11

Synthesis of Compound I-0011

(757) ##STR00115##
Step 1

(758) The compound 22 (7.2 g, 39.3 mmol) was dissolved in tetrahydrofuran (28 mL). A 1 mol/L aqueous solution of sodium hydroxide (56 mL, 56 mmol) was added to the solution. The mixture was stirred at room temperature for 1.5 hours. A 2 mol/L hydrochloric acid solution (6 mL, 12 mmol) was added to the mixture. The mixture was extracted with ethyl acetate. The organic layer was washed by water and brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, Ethyl acetate-hexane was added to the obtained residue. The precipitated solids were filtered to give the compound 23 (3.4 g, yield 53%).

(759) .sup.1H-NMR (CDCl3) δ: 8.07 (s, 1H)

(760) Step 2

(761) The compound 23 (3.0 g, 18.18 mmol) was dissolved in dichloromethane (30 mL). DIEA (4.76 mL, 27.30 mmol) was added to the solution. The mixture was stirred until dissolved. Then, benzyl bromide (2.34 mL, 20.00 mmol) was added to the mixture. The mixture was stirred at room temperature for 1.5 hours. After the mixture was left standing overnight, the reaction mixture was poured into water. The mixture was extracted with ethyl acetate. The organic layer was washed by 5% aqueous solution of citric acid and water, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. Ethyl ether was added to the obtained residue. The obtained solid was filtered to give the compound 24 (1.5 g, yield 32%).

(762) .sup.1H-NMR (CDCl3) δ: 5.22 (s, 2H), 7.20-7.30 (m, 2H), 7.40-7.50 (m, 3H), 7.58 (s, 1H)

(763) Step 3

(764) The compound 24 (100 mg, 0.39 mmol) was dissolved in dioxane (2 mL). 3-Chloro-2-methylaniline (83 mg, 0.59 mmol) was added to the solution. The mixture was stirred under microwave irradiation at 130° C. for 10 minutes. The solvent was evaporated under reduced pressure. The obtained residue was purified by silica-gel column chromatography (ethyl acetate-n-hexane) to give the compound I-0011 (73 mg, yield 52%).

(765) .sup.1H-NMR (CDCl3) δ: 2.04 (s, 3H), 5.08 (s, 2H), 6.66 (d, J=7.2 Hz, 1H), 7.05-7.14 (m, 2H), 7.30-7.44 (m, 6H), 7.57 (s, 1H)

Example 12

Synthesis of Compound I-0012

(766) ##STR00116##
Step 1

(767) The compound 25 (5.0 g, 30.7 mmol) was dissolved in tetrahydrofuran (10 mL). A 1 mol/L aqueous solution of sodium hydroxide (46 mL, 46.0 mmol) was added to the solution. The mixture was stirred at room temperature for 24 hours. The reaction mixture was washed by diethyl ether. Under ice cooling, a 2 mol/L aqueous solution of hydrochloric acid was added to the mixture to adjust the pH to 3. The precipitated solids were filtered, and washed by cold water. The obtained solid was dried to give the compound 26 (1.9 g, yield 42.8%).

(768) .sup.1H-NMR (DMSO-d.sub.6) δ: 1.96 (s, 3H), 7.94 (s, 1H), 12.80-13.80 (br, 1H).

(769) Step 2

(770) The compound 26 (500 mg, 3.46 mmol) was dissolved in dichloromethane (5 mL). DIEA (904 μL, 0.19 mmol) and benzyl bromide (494 μL, 4.16 mmol) were added to the solution. The mixture was stirred at room temperature for 1 day. A 2 mol/L aqueous solution of hydrochloric acid was added to the mixture. The mixture was extracted with chloroform. The organic layer was washed by brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by silica-gel column chromatography (chloroform-methanol) to give the compound 27 (416 mg, yield 51.2%). 41 NMR (CDCl.sub.3) δ: 2.00 (s, 3H), 5.17 (s, 2H), 7.18-7.24 (m, 3H), 7.37-7.48 (m, 3H>.

(771) Step 3

(772) The compound 27 (50 mg, 0.213 mmol) was dissolved in dioxane (3 mL). 3-Chloro-2-methylaniline (151 mg, 1.07 mmol) was added to the solution. The mixture was stirred under microwave irradiation at 100° C. for 120 minutes. Insoluble materials were filtered off, and rinced by ethyl acetate. The filtrate was evaporated under reduced pressure. The obtained residue was purified by silica-gel column chromatography (hexane-ethyl acetate) to give the compound I-0012 (52 mg, yield 71.8%).

(773) .sup.1H-NMR (CDCl.sub.3) δ: 1.86 (s, 3H), 2.04 (s, 3H), 5.05 (s, 2H), 6.67 (d, J=6.0 Hz, 1H), 7.02-7.12 (m, 3H), 7.32-7.43 (m, 5H), 7.46-7.52 (br, 1H).

Example 13

Synthesis of Compound I-0013

(774) ##STR00117##
Step 1

(775) Under nitrogen atmosphere, 2-(trimethylsilyl)ethanol (2.5 mL, 17.3 mmol) was dissolved in tetrahydrofuran (25 mL). Under ice cooling, sodium hydride (60% oil dispersion, 506 mg, 12.6 mmol) was added to the solution. The mixture was stirred at room temperature for 1 hour. Under ice cooling, the tetrahydrofuran solution (5 mL) of the compound 28 (2.0 g, 11.5 mmol) was added dropwise to the mixture. The mixture was stirred at room temperature for 5.5 hours. A 2 mol/L aqueous solution of hydrochloric acid was added to the mixture. The mixture was extracted with ethyl acetate. The organic layer was washed by brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by silica-gel column chromatography (hexane-ethyl acetate) to give the compound 29<1.07 g, yield 36.4%).

(776) .sup.1H-NMR (CDCl.sub.3) δ: 0.11 (s, 9H), 1.18-1.26 (m, 2H), 4.63-4.67 (m, 2H), 8.59 (s, 1H).

(777) Step 2

(778) The compound 29 (693 mg, 2.71 mmol) was dissolved in dioxane (10 mL). 3-Chloro-2-methylaniline (537 mg, 3.79 mmol), palladium acetate (61 mg, 0.271 mmol), Xantphos (235 mg, 0.406 mmol) and cesium carbonate (1.24 g, 3.81 mmol) were added to the solution. The mixture was stirred under reflux for 1.5 hours. A 2 mol/L aqueous solution of hydrochloric acid was added to the mixture. The mixture was extracted with ethyl acetate. The organic layer was washed by the saturated aqueous solution of sodium hydrogen carbonate and brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by silica-gel column chromatography (hexane-ethyl acetate) to give the compound 30 (153 mg, yield 15.6%).

(779) .sup.1H-NMR (CDCl.sub.3) δ: 0.06 (s, 9H), 1.14 (t, J=8.4 Hz, 2H), 2.36 (s, 3H), 4.47 (t, J=8.4 Hz, 2H), 7.02-7.11 (br, 1H). 7.17 (t, J=8.0 Hz, 1H), 7.27 (d, J=8.0 Hz, 1H), 7.69 (d, J=8.0 Hz, 1H), 8.38 (s, 1H).

(780) Step 3

(781) The compound 30 (150 mg, 0.416 mmol) was dissolved in tetrahydrofuran (1 mL). Tetrabutyl ammonium fluoride (1 mol/L tetrahydrofuran solution, 831 μL, 0.831 mmol) was added to the solution. The mixture was stirred at room temperature for 1 day. The solvent was evaporated under reduced pressure. The obtained residue was purified by silica-gel column chromatography (chloroform-methanol) to give the compound 31 (92 mg, yield 84.9%).

(782) .sup.1H-NMR (DMSO-d.sub.6) δ: 2.22 (s, 3H), 7.24 (t, J=8.0 Hz, 1H), 7.37 (d, J=8.0 Hz, 2H), 8.25 (s, 1H), 9.25-9.90 (br, 1H), 11.70-12.60 (br, 1H).

(783) Step 4

(784) The compound 31 (45 mg, 0.173 mmol) was dissolved in dichloromethane (3 mL). DIEA (90 μL, 0.518 mmol) and benzyl bromide (41 μL, 0.345 mmol) were added to the solution. The mixture was stirred at room temperature for 2 days. The solvent was evaporated under reduced pressure. The obtained residue was purified by silica-gel column chromatography (hexane-ethyl acetate) to give the compound I-0013 (14 mg, yield 23.1%).

(785) .sup.1H-NMR (CDCl.sub.3) δ: 2.02 (s, 3H), 5.15 (s, 2H), 6.65 (d, J=8.0 Hz, 1H), 7.10-7.20 (m, 2H), 7.34-7.49 (m, 614), 7.55-7.61 (br, 1H), 7.79 (s, 1H).

Example 14

Synthesis of Compound I-0015

(786) ##STR00118##

(787) Under nitrogen atmosphere, the compound I-0014 (15 mg, 0.037 mmol) obtained by the similar synthesis of Example 2 was dissolved in dichloromethane (2 mL). A 1 mol/L boron tribromide (8.33 μL, 0.088 mmol) was added to the solution. The mixture was stirred at room temperature for 3 hours. The saturated aqueous solution of sodium hydrogen carbonate was added to the mixture. The mixture was extracted with ethyl acetate. The organic layer was washed by brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by silica-gel column chromatography (n-hexane-ethyl acetate) to give the compound I-0015 (8 mg, yield 55%). 1H-NMR (DMSO-D6) δ: 1.95 (3H, s). 4.80 (1H, d, J=15.8 Hz), 5.03 (1H, d, J=15.8 Hz), 6.82 (1H, d, J=7.5 Hz), 7.09-7.20 (3H, m), 7.64-7.61 (2H, m), 7.70 (1H, d, J=7.8 Hz), 7.97 (1H, d, J=7.8 Hz)

Example 15

Synthesis of Compound I-0016

(788) ##STR00119##
Step 1

(789) The compound 15 (2.0 g, 7.98 mmol) was dissolved in dichloromethane (40 mL). The solution was cooled to 0° C. Boron tribromide (dichloromethane solution, 1 mol/L) was added to the solution. The mixture was stirred at 0° C. for 1 hour. The saturated aqueous solution of sodium hydrogen carbonate and chloroform were added to the reaction mixture. The mixture was stirred at room temperature for 15 minutes. A 2 mol/L hydrochloric acid solution was added to the reaction mixture. The mixture was extracted with chloroform. The organic layer was dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. Ethyl acetate and hexane were added to the obtained residue. The resulting powder was filtered to give the compound 32 (2.0 g) as a crude product.

(790) LC-MS (Condition [1]): RT=1.07, 236 [M+H].sup.+

(791) Step 2

(792) The compound 32 (200 mg, 0.845 mmol) was dissolved in NMP (4.0 mL). 2,2,2-Trifluoroethyl trifluoromethanesulfonate (1960 mg, 8.45 mmol) and potassium carbonate (350 mg, 2.54 mmol) wore added to the solution. The mixture was stirred at 50° C. for 4 hours. Water was added to the reaction mixture. The mixture was extracted with chloroform. The organic layer was dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure.

(793) The obtained crude product was dissolved in NMP (4.0 mL). 3-Chloro-2-methylaniline (0.200 mL, 1.69 mmol) was added to the solution. The mixture was stirred under microwave irradiation at 130° C. for 1.0 minutes. Water was added to the reaction mixture. The mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by reverse-phase silica-gvl column chromatography (water-acetonitrile) to give the compound I-0016 (22 mg, yield 6%) as a white powder.

(794) LC-MS (Condition [1]): RT=2.03, 424 [M+H].sup.+

(795) .sup.1H-NMR (DMSO-D6) δ: 1.82 (3H, s), 4.69 (2H, q, J=9.0 Hz), 5.22 (2H, s), 7.05-7.44 (8H, m), 7.74 (1H, s), 8.73 (1H, s).

Example 16

Synthesis of Compound I-0018

(796) ##STR00120##
Step 1

(797) The compound 33 (1.0 g, 4.67 mmol) was dissolved in dichloromethane (10 mL). DIEA (1.22 mL, 7.00 mmol) and benzyl bromide (665 μL, 5.60 mmol) were added to the solution. The mixture was stirred at room temperature for 0.1 day. A 2 mol/L aqueous solution of hydrochloric acid was added to the mixture. The mixture was extracted with ethyl acetate. The organic layer was washed by brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by silica-gel column chromatography (chloroform-methanol) to give the compound 34 (1.09 g, yield 76.7%). .sup.1H-NMR (CDCl.sub.3) δ: 1.34 (t, J=6.8 Hz, 3H), 2.61 (s, 3H), 4.33 (q, J=6.8 Hz, 2H), 5.09 (s, 2H), 7.21-7.26 (m, 2H>. 7.38-7.47 (m, 3H), 8.06 (s, 1H).

(798) Step 2

(799) The compound 34 (927 mg, 3.05 mmol) was dissolved in tert-butanol (18 mL). Acetic acid (2.6 mL, 45.7 mmol) and 3-chloro-2-methyl anilino (647 mg, 4.57 mmol) were added to the solution. The mixture was stirred under reflux for 96 hours. After cooled to room temperature, the mixture was diluted with ethyl acetate. The mixture was washed by the saturated aqueous solution of sodium hydrogen carbonate and brine. The mixture was dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by silica-gel column chromatography (hexane-ethyl acetate) to give the compound I-0017 (770 mg, yield 63.5%).

(800) .sup.1H-NMR (CDCl.sub.3) δ: 1.33 (t, J=7.2 Hz, 3H), 1.96 (s, 3H), 4.31 (q, J=7.2 Hz, 2H), 5.16 (s, 2H), 6.64 (d, J=7.6 Hz, 1H), 7.06-7.17 (m, 2H), 7.35-7.47 (m, 6H), 8.32 (s, 1H).

(801) Step 3

(802) The compound I-0017 (757 mg, 1.90 mmol) was dissolved in a mixed solution of ethanol (5.7 mL) and tetrahydrofuran (5.7 mL). A 1 mol/L aqueous solution of lithium hydroxide (5.7 mL, 5.7 mmol) was added to the solution. The mixture was stirred at 50° C. for 2.5 hours. A 10% aqueous solution of citric acid was added to the mixture. The mixture was extracted with ethyl acetate. The organic layer was washed by brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The obtained solids were washed by IPE to give the compound I-0018 (631 mg, yield 89.7%).

(803) .sup.1H-NMR (CDCl.sub.3) δ: 1.99 (s, 3H), 5.19 (s, 2H), 6.66 (d, J=7.6 Hz, 1H), 7.10-7.21 (m, 2H), 7.35-7.49 (m, 511), 7.55-7.90 (br, 1H), 8.52 (s, 1H), 11.78-12.30 (br, 1H).

Example 17

Synthesis of Compound I-0019

(804) ##STR00121##

(805) 4-aminotetrahydro-2H-pyran hydrochloride (41 mg, 0.3 mmol), 1-hydroxybenzotriazole (41 mg, 0.3 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (58 mg, 0.3 mmol) were added to a mixed solution of the compound I-0018 (74 mg, 0.2 mmol) and DMF (2 mL). Then, triethylamine (0.042 mL, 0.3 mmol) was added to the mixture. The mixture was stirred at room temperature for 8 hours. Water was added to the reaction mixture. The mixture was extracted with ethyl acetate. The organic layer was washed by the saturated aqueous solution of sodium hydrogen carbonate and brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. Ethyl acetate and hexane were added to the obtained residue. The resulting powder was filtered to give the compound I-0019 (0.08 g, yield 88%) as a white powder.

(806) .sup.1H-NMR, (DMSO-d6) δ: 1.40-1.46 (211, m), 1.78-1.83 (5H, m), 3.35-3.44 (2H, m), 3.77-3.81 (2H, m), 3.93 (1H, m), 5.26 (2H, brs), 6.68 (1H, brs), 7.10 (2H, brs), 7.34-7.39 (5H, m), 8.59 (1H, brs), 10.43 (1H, brs).

Example 18

Synthesis of Compound I-0020

(807) ##STR00122##

(808) The compound I-0018 (50 mg, 0.135 mmol) was dissolved in toluene (5.0 mL). Methanol (55 μL, 1.35 mmol), triethylamine (22 μL, 0.162 mmol) and DPPA (32 μL, 0.149 mmol) were added to the solution. The mixture was stirred at 100° C. for 4 hours and then stirred under reflux for 1 hour. The saturated aqueous solution of sodium hydrogen carbonate was added to the mixture. The mixture was extracted with ethyl acetate. The organic layer was washed by brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by silica-gel column chromatography (hexane-ethyl acetate) to give the compound I-0020 (20 mg, yield 37.1%).

(809) .sup.1H-NMR (DMSO-d.sub.6) δ: 1.88 (s, 3H), 3.61 (s, 3H), 5.15-5.34 (br, 2H), 6.93-7.51 (m, 8H), 7.95-8.20 (br, 1H), 8.01 (s, 1H), 8.72-9.00 (br, 1H).

Example 19

Synthesis of Compound I-0021

(810) ##STR00123##

(811) DPPA (0.103 mL. 0.48 mmol) and triethylamine (0.067 mL, 0.48 mmol) were added to a mixed solution of the compound I-0018 (148 mg, 0.4 mmol), dioxane (1 mL) and tert-butanol (0.5 mL). The mixture was stirred under reflux for 2 hours. Water was added to the reaction mixture. The mixture was extracted with ethyl acetate. The organic layer was washed by brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by silica-gel column chromatography (ethyl acetate-hexane). Ethyl acetate and hexane were added to the obtained residue. The resulting powder was filtered to give the compound I-0021 (50 mg, yield 28%) as a white powder.

(812) .sup.1H-NMR (CDCl3) δ: 1.49 (1.51) (9H, s), 1.98 (1.75) (3H, s), 5.06 (5.03) (2H, a), 5.83-8.18 (10H, m).

Example 20

Synthesis of Compound I-0022

(813) ##STR00124##

(814) A 4 mol/L hydrochloric acid-dioxane solution (0.10 mL, 0.4 mmol) was added to a mixed solution of the compound I-0021 (35 mg, 0.08 mmol) and dioxane (1 mL). The mixture was stirred at 50° C. for 2 hours. The saturated aqueous solution of sodium hydrogen carbonate (20 mL) was added to the reaction mixture. The mixture was extracted with ethyl acetate (50 mL). The organic layer was washed by brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by silica-gel column chromatography (ethyl acetate-hexane) to give the compound I-0022 (23 mg, yield 84%) as a white powder.

(815) 1H-NMR (CDCl3) δ: 2.07 (2H, s), 3.24 (2H, brs), 5.01 (2H, s), 6.72 (2H, brs), 7.05-7.10 (2H, m), 7.34-7.42 (5H, m), 7.61 (1H, brs).

Example 21

Synthesis of Compound I-0023

(816) ##STR00125##
Step 1

(817) DIEA (11.5 mL, 65.7 mmol) and benzyl bromide (6.2 mL, 52.6 mmol) were added to a suspension of the compound 35 (10 g, 43.8 mmol) in dichloromethane (10 mL). The mixture was stirred at room temperature for 20 hours. A 2 mol/L hydrochloric acul solution was added to the reaction mixture. The mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. Hexane was added to the obtained residue. The resulting powder was filtered to give the compound 36 (12.3 g) as a crude product.

(818) LC-MS (Condition [1]): RT=1.46, 319 [M+H].sup.+

(819) Step 2

(820) 3-chloro-2-methylaniline (100 mg, 0.707 mmol) was added to an acetic acid (0.40 mL, 7.07 mmol) solution of the compound 36 (0.15 g, 0.471 mmol). The mixture was stirred under reflux for 4 hours. Water was added to the reaction mixture. The mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by reverse-phase silica-gel column chromatography (water-acetonitrile) to give the compound I-0023 (41.0 mg, yield 21%) as a white powder.

(821) LC-MS (Condition [3]): RT=2.33, 412 [M+H].sup.+

(822) 1H-NMR (DMSO-D6) δ: 1.17 (3H, t, J=7.2 Hz), 1.86 (3H, s), 3.20 (2H, s), 4.05 (2H, q, J=7.1 Hz), 5.06 (2H, br s), 6.55-7.45 (8H, m), 7.79 (1H, s), 9.93 (1H, s).

Example 22

Synthesis of Compound I-0024

(823) ##STR00126##

(824) Lithium borohydride (10.6 mg, 0.486 mmol) was added to a tetrahydrofuran (2.0 mL) solution of the compound I-0023 (1.00 mg, 0.243 mmol). The mixture was stirred at room temperature for 2 hours. Lithium borohydride (10.6 mg, 0.486 mmol) was further added to the mixture. The mixture was stirred at room temperature for 2 hours. The saturated aqueous solution of ammonium was added to the reaction mixture. The mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by reverse-phase silica-gel column chromatography (water-acetonitrile) to give the compound I-0024 (72.9 mg, yield 99%) as a white powder.

(825) LC-MS (Condition [3]): RT=1.87, 370 [M+H].sup.+

(826) 1H-NMR (DMSO-D6) δ: 1.85 (3H, s), 2.32 (2H, t, J=6.5 Hz), 3.46 (2H, q, J=6.1 Hz). 4.58 (1H, br s). 5.05 (2H, br s), 6.55-7.70 (9H, m), 9.66 (1H, s).

Example 23

Synthesis of Compound I-0026

(827) ##STR00127##
Step 1

(828) A 2 mol/L aqueous solution of sodium hydroxide (9.71 mL, 19.42 mmol) was added to a tetrahydrofuran (20 mL) and methanol (20 mL) solution of the compound I-0023 (2.0 g, 4.86 mmol). The mixture was stirred at room temperature for 0.1 hour. The solvent in the reaction mixture was evaporated under reduced pressure. A 2 mol/L hydrochloric acid solution was added to the mixture. The resulting powder was filtered to give the compound I-0025 (1.75 g, yield 94%) as a crude product.

(829) LC-MS (Condition [3]): RT=1.79, 384 [M+H]).sup.+

(830) .sup.1H-NMR (DMSO-D6) δ: 1.88 (3H, s), 3.17 (2H, s), 5.16 (2H, br s), 6.70-7.60 (8H, m), 7.83 (1H, s), 9.88 (1H, br s), 12.30 (1H, br s).

(831) Step 2

(832) HATU (149 mg, 0.391 mmol), ammonium chloride (20.9 mg, 0.391 mmol) and triethylamine (0.10 mL, 0.782 mmol) were added to a DMF (2.0 mL) solution of the compound I-0025 (100 mg, 0.261 mmol). The mixture was stirred at room temperature for 1.5 hours. The saturated aqueous solution of sodium hydrogen carbonate was added to the reaction mixture. The mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate. The solvent, was evaporated under reduced pressure. The obtained residue was purified by reverse-phase silica-gel column chromatography (water-acetonitrile) to give the compound I-0026 (100.0 mg, yield 96%) as a white powder.

(833) LC-MS (Condition [3]): RT=1.77, 383 [M+H].sub.+

(834) 1H-NMR (DMSO-D6) δ: 1.87<3H, s), 2.98 (2H, s), 5.08 (2H, s), 6.65-7.50 (10H, m), 7.69 (1H, s), 9.73 (1H, br s).

Example 24

Synthesis of Compound I-0028

(835) ##STR00128##
Step 1

(836) 3-Chloro-2-methylaniline (496 mg, 3.51 mmol) was added to a dioxane (15 mL) solution of the compound 37 (0.7 g, 2.33 mmol). The mixture was stirred under microwave irradiation at 1.30° C. for 1.0 minutes. The solvent in the reaction mixture was evaporated under reduced pressure. Ethyl acetate and hexane were added to the residue. The resulting powder was filtered to give the compound I-0027 (850 mg) as a crude product.

(837) LC-MS (Condition [1]): RT=1.96, 405 [M+H].sup.30

(838) Step 2

(839) Phenylboronic acid (36.2 mg, 0.297 mmol). [1,1′-bis(di-tert-butylphosphino)ferrocene]palladium(II) dichloride (8.0 mg, 0.012 mmol) and sodium carbonate (0.49 mL, 0.988 mmol) were added to a DMF (15 mL) solution of the compound I-0027 (100 mg, 0.247 mmol). The mixture was stirred at 100° C. for 3 hours. Water was added to the reaction mixture. The mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by reverse-phase silica-gel column chromatography (water-acetonitrile) to give the compound I-0028 (1.4.3 mg, yield 14%) as a white powder.

(840) LC-MS (Condition [3]): RT=2.73, 402 [M+H].sup.+

(841) 1H-NMR (DMSO-D6) δ: 1.93 (311, s), 4.92 (2H, dd, J=46.8, 14.9 Hz), 7.01-7.33 (13H, m), 7.61 (1H, s), 9.84 (1H, s).

Example 25

Synthesis of Compound I-0029

(842) ##STR00129##
Step 1

(843) Under nitrogen atmosphere, 2-(trimethylsilyl)ethanol (2.85 mL, 19.8 mmol) was dissolved in tetrahydrofuran (30 mL). Sodium hydride (00% oil dispersion, 032 mg, 15.8 mmol) was added to the solution under ice cooling. The mixture was stirred at room temperature for 1 hour. A 15 mL of tetrahydrofuran solution of the compound 38 (3.0 g, 13.2 mmol) was added dropwise to the mixture under ice cooling. The mixture was stirred at room temperature for 2.5 hours. A 2 mol/L aqueous solution of hydrochloric acid was added to the mixture. The mixture was extracted with ethyl acetate. The organic layer was washed by brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by silica-gel column chromatography (hexane-ethyl acetate) to give the compound 39 (3.81 g, yield 93.5%).

(844) 1H-NMR (CDCl.sub.3) δ: 0.10 (s, 9H), 1.12 (t, J=8.0 Hz, 2H), 4.57 (t, J=8.0 Hz, 2H), 8.41 (s, 1H).

(845) Step 2

(846) Under nitrogen atmosphere, the compound 39 (500 mg, 1.62 mmol) was dissolved in dioxane (15 mL). Phenylboronic acid (276 mg, 2.26 mmol), [1,1′-bis(diphenylphosphino)ferrocene]palladium(II) dichloride dichloromethane adduct (132 mg, 0.161 mmol) and a 2 mol/L aqueous solution of sodium carbonate (2.4 mL, 4.8 mmol) were added to the solution. The mixture was stirred under reflux for 4 hours. After cooled to room temperature, water was added to the mixture. The mixture was extracted with ethyl acetate. The organic layer was washed by brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by silica-gel column chromatography (hexane-ethyl acetate) to give the compound 40 (407 mg, yield 82.1%).

(847) Step 3

(848) The compound 40 (181 mg, 0.590 mmol) was dissolved in dioxane (4 mL). 2-Chloro-3-trifluoromethylphenol (1.51 mg, 0.767 mmol) and cesium carbonate (288 mg, 0.885 mmol) were added to the solution. The mixture was stirred under microwave irradiation at 100° C. for 4.5 hours. Water was added to the mixture. The mixture was washed by ethyl acetate. The organic layer was washed by brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by silica-gel column chromatography (hexane-ethyl acetate) to give the compound 41 (132 mg, yield 47.9%).

(849) .sup.1H-NMR (CDCl.sub.3) δ: −0.05 (s, 9H), 1.06 (t, J=8.0 Hz, 2H), 4.38 (t, J=8.0 Hz, 2H), 7.20-7.52 (m, 7H), 7.64 (d, J=7.6 Hz, 1H), 8.26 (s, 1H).

(850) Step 4

(851) The compound 41 (127 mg, 0.272 mmol) was dissolved in tetrahydrofuran (0.5 mL). Tetrabutyl ammonium fluoride (1 mol/L tetrahydrofuran solution, 408 μL, 0.408 mmol) was added to the solution. The mixture was stirred at room temperature for 4 days. The solvent was evaporated under reduced pressure. The obtained residue was purified by silica-gel column chromatography (chloroform-methanol) to give the compound 42 (77 mg, yield 77.2%).

(852) .sup.1H-NMR (DMSO-d.sub.6) δ: 7.30-7.43 (m, 3H), 7.58-7.72 (m, 3H), 7.82-8.06 (m, 3H), 13.20-13.65 (br, III).

(853) Step 5

(854) The compound 42 (75 mg, 0.205 mmol) was dissolved in dichloromethane (2 mL). DIEA (54 μL, 0.307 mmol) and benzyl bromide (32 μL, 0.266 mmol) were added to the solution. The mixture was stirred at room temperature for 1 day. A 2 mol/L aqueous solution of hydrochloric acid was added to the mixture. The mixture was extracted with chloroform. The organic layer was washed by brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by silica-gel column chromatography (chloroform-methanol) to give the compound I-0029 (78 mg, yield 83.5%).

(855) .sup.1H-NMR (DMSO-d.sub.6) δ: 5.35 (s, 2H), 7.31-7.51 (m, 8H), 7.61-7.78 (m, 4H), 7.87 (d, J=8.0 Hz, 1H), 8.34 (s, 1H).

Example 26

Synthesis of Compound I-0030

(856) ##STR00130##

(857) The compound 43 (200 mg, 0.66 mmol) obtained by the similar synthesis of Example 2 was dissolved in dioxane (6 mL). The compound 14 (117 mg, 0.66 mmol), palladium acetate (15 mg, 0.07 mmol), Xantphos (57 mg, 0.10 mmol) and cesium carbonate (209 mg, 0.92 mmol) were added to the solution. Under nitrogen atmosphere, the mixture was stirred under reflux for 1.5 hours. A 5% aqueous solution of citric acid was added to the mixture. The mixture was extracted with ethyl acetate. The organic layer was washed by the aqueous solution of sodium hydrogen carbonate, water and brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by silica-gel column chromatography (ethyl acetate-n-hexane) to give the compound I-0030 (70 mg, yield 24%).

(858) .sup.1H-NMR (CDCl3) δ: 2.01 (s, 3H), 2.83 (s, 3H), 3.35 (s, 3H), 4.65 (s, 1H), 5.30 (s, 2H), 5.87 (s, 1H), 6.95-7.05 (m, 2H>, 7.46 (s, 1H), 7.76 (s, 1H)

Example 27

Synthesis of Compound I-0031

(859) ##STR00131##
Step 1

(860) The compound 44 (3 g, 17.24 mmol) was dissolved in DMF (20 mL). DIEA (3.61 mL, 20.69 mmol) and 2-methylbenzyl bromide (2.43 mL, 18.10 mmol) were added to the solution. The mixture was stirred at room temperature for 7 hours. After the mixture was left standing overnight, water was added to the mixture. The mixture was extracted with ethyl acetate. The organic layer was washed by brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was solidified with ethyl acetate and IPE. The precipitated solids were filtered, and dried to give the compound 45 (812 mg, yield 15%).

(861) LC-MS (Condition [2]): RT=1.40, 278 [M+H].sup.30

(862) Step 2

(863) The compound 45 (30 mg, 0.095 mmol) was dissolved in DMF (1 mL). Cesium carbonate (93 mg, 0.286 mmol) and 2-chloro-3-trifluoromethyl-phenol (19 μL, 0.143 mmol) were added to the solution. The mixture was stirred at 70° C. for 5 hours. Then, the mixture was stirred at 100° C. for 16 hours. Water was added to the reaction mixture. The mixture was extracted with chloroform-methanol (9/1). The solvent was evaporated under reduced pressure. The obtained residue was purified by a preparative high performance liquid chromatography to give the compound I-0031 (9.4 mg, yield 25%).

(864) 1H-NMR (CDCl3) δ: 2.31 (311, s), 5.08 (1H, s), 5.31 (2H, s), 6.08 (1H, d, J=7.6 Hz), 6.94 (1H, s), 7.23 (3H, s), 7.62-7.67 (2H, m), 7.73 (1H, d, J=7.6 Hz), 7.85 (1H, d, J=7.3 Hz)

Example 28

Synthesis of Compound I-0032

(865) ##STR00132##

(866) Under nitrogen atmosphere, the compound 45 (40 mg, 0.127 mmol) was dissolved in dioxane (1 mL). 3′Chloro-2-methylaniline (34.8 mg, 0.178 mmol), palladium acetate (2.85 mg, 0.013 mmol), Xantphos (11.04 mg, 0.019 mmol) and cesium carbonate (104 mg, 0.318 mmol) were added to the solution. The mixture was stirred under reflux for 5 hours. Water was added to the reaction mixture. The mixture was extracted with ethyl acetate. The organic layer was washed by brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by a preparative high performance liquid chromatography to give the compound I-0032 (9.4 mg, yield 19%).

(867) LC-MS (Condition [2]): RT=1.99, 393 [M+H].sup.+

Example 29

Synthesis of Compound I-0033

(868) ##STR00133##
Step 1

(869) Dimethylsulfone acid (1.06 mL, 1.11 mmol) was added dropwise to a 10% aqueous solution of potassium hydroxide (651 mL) of the compound 46 (150 g, 1.06 mmol) at 3° C. to 5° C. The mixture was stirred at 0° C. to 5° C. for 4 hours. The precipitates were filtered, and washed by IPE. The obtained solids were dried under reduced pressure to give the compound 47 (1.065 g, yield 65%).

(870) Step 2

(871) 2,2,2,6-tetramethylpiperidine 1-oxyl (2.60 g, 16.7 mmol) and sodium hydrogen carbonate (14.0 g, 167 mmol) were added to a tetrahydrofuran solution (1.20 mL) of the compound 47 (52.0 g, 333 mmol) at 0° C. Then, a 5% aqueous solution of sodium hypochlorite (1.15 L, 833 mmol) was added dropwise to the mixture at 0° C. to 15° C. over 2.5 hours. The mixture was stirred at 5° C. for 45 minutes. Sodium sulfite (35 g) was added to the mixture. The reaction mixture was washed by ethyl acetate. Concentrated hydrochloric acid was added to the obtained aqueous layer. The white precipitated solids were filtered, and dried under reduced pressure to give the compound 48 (20.0 g, yield 35%).

(872) Step 3

(873) 3-Chloro-4-fluorobenzylamine (20 g, 125 mmol) and a 2 mol/L aqueous solution of sodium hydroxide (80 mL, 160 mmol) were added to an ethanol (80 mL) solution of the compound 48 (19.4 g, 114 mmol) at room temperature. The mixture was stirred at 90° C. for 1 hour. The reaction mixture was concentrated under reduced pressure. Water was added to the residue. The mixture was washed by chloroform. A 2 mol/L hydrochloric acid solution was added to the obtained aqueous layer. The yellow precipitated solids were filtered, and dried under reduced pressure to give the compound 49 (18.6 g, yield 62%).

(874) .sup.1H NMR (d.sub.6-DMSO) δ: 3.72 (s, 3H), 5.51 (s, 2H), 6.67 (s, 1H), 7.18 (ddd, J=8.5, 4.5, 1.8 Hz, 1H), 7.42 (dd, J=9.0, 8.5 Hz, 1H), 7.46 (dd, J=7.0, 1.8 Hz, 1H), 7.78 (s, 1H).

(875) Step 4

(876) Iodine (5.86 g, 23.1 mmol) was added to a dimethyl sulfoxide (40 mL) solution of the compound 49 (6.00 g, 1.14 mmol) at room temperature. The mixture was stirred at 120° C. for 3 hours. After cooled to room temperature, a 5% aqueous solution of sodium thiosulfate was added to the reaction mixture. The mixture was extracted with ethyl acetate. The organic layer was washed by brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by silica-gel column chromatography (chloroform-methanol) to give the compound 50 (3.10 g, yield 39%) as colorless foam.

(877) .sup.1H-NMR (d.sub.6-DMSO) δ: 3.65 (s, 3H), 5.36<s, 2H), 6.77 (s, 1H), 7.11 (ddd, J=8.5, 4.5, 2.3 Hz, 1H), 7.43 (dd, J=7.0, 2.3 Hz, 1H), 7.45 (dd, J=9.0, 8.5 Hz, 1H), 7.88 (s, 1H).

(878) Step 5

(879) The compound 14 (50 mg, 0.279 mmol), Xantphos (29 mg, 0.051 mmol), palladium acetate (8.6 mg, 0.038 mmol) and cesium carbonate (207 mg, 0.635 mmol) were added to a 1,4-dioxane (2 mL) solution of the compound 50 (100 mg, 0.254 mmol) at room temperature. The mixture was stirred at 80° C. for 5 hours. After cooled to room temperature, the reaction mixture was poured into brine. The mixture was extracted with ethyl acetate. The organic layer was washed by brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by silica-gel column chromatography (chloroform-methanol) to give the compound I-0033 (60 mg, yield 53%) as colorless solids.

(880) .sup.1H-NMR (CDCl.sub.3) δ: 2.05 (s, 3H), 2.80 (s, 3H), 3.79 (s, 3H), 6.04 (s, 2H), 5.37 (s, 1H), 5.83 (s, 1H), 6.81 (s, 1H), 7.05 (m, 1H), 7.20 (dd, J=8.5, 8.5 Hz, 1H), 7.25 (m, 1H), 7.29 (m, 1H), 7.72 (s, 1H).

Example 30

Synthesis of Compound I-1118

(881) ##STR00134##
Step 1

(882) The compound 51 (900 mg, 5.35 mmol) was dissolved in acetonitrile (10 mL). Silver(II) fluoride (2.34 g, 16.06 mmol) was added to the solution. The mixture was vigorously stirred at room temperature for 1.5 hours. The reaction mixture was warmed to 50° C., and vigorously stirred for 3 hours. Silver(II) fluoride (1.56 g, 10.70 mmol) was further added to the mixture. The mixture was vigorously stirred at 50° C. for 2.5 hours. Silver(II) fluoride (0.78 g, 5.35 mmol) was further added to the mixture. The mixture was vigorously stirred at 50° C. for 2 hours. Under ice cooling, the saturated aqueous solution of sodium hydrogen carbonate was added to the reaction mixture. Insoluble materials were filtered off. The filtrate was extracted with ethyl acetate. The organic layer was washed by water and brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by silica-gel column chromatography (ethyl acetate/hexane) to give the compound 52 (374 mg, yield 38%).

(883) LC-MS (Condition [3]): RT=1.60, 187 [M+H].sup.+

(884) Step 2

(885) The compound 52 (370 mg, 1.98 mmol) was dissolved in methanol (3 mL). A 10% palladium-carbon (containing 50% water, 423 mg, 0.199 mmol) was added to the solution. The mixture was stirred under stream of 1 atm hydrogen at room temperature for 52 hours. The reaction mixture was filtered through Celite. The solvent was evaporated under reduced pressure to give the crude product of the compound 53 (267 mg, yield 77%).

(886) 1H-NMR (DMSO-D6) δ: 2.09 (s, 3H), 3.74 (s, 3H), 4.94 (s, 2H), 6.86 (d, 1H)

(887) Step 3

(888) The crude product of the compound 3 (50 mg, 0.32 mmol) was dissolved in dioxane (1 mL). 2-Chloro-1-(3,5-difluorobenzyl)-5-fluoropyrimidin-4(1H)-one (88 mg, 0.32 mmol) was added to the solution. The mixture was stirred under microwave irradiation at 130° C. for 15 minutes. Water was added to the reaction mixture. The precipitated solids were filtered. The crude was resolidized by EtOAc. The obtained precipitated solids were filtered, and then dried to give the compound I-1118 (43.1 mg, yield 34%).

(889) LC-MS (Condition [2]): ET=1.47, 395 [M+H].sup.+

(890) 1H-NMR (DMSO-D6) δ: 8.82 (10.70) (1H, s), 8.09 (1H, s), 7.45 (7.11) (1H, s), 7.24 (1H, brs), 7.11 (2H, d, J=5.0 Hz), 5.20 (2H, brs), 3.81 (3H, s), 1.90 (3H, s).

Example 31

Synthesis of Compound I-1138

(891) ##STR00135##
Step 1

(892) The compound 54 (2 g, 14.1 mmol) was dissolved in phosphoryl chloride (2.62 mL, 28.1 mmol). Under ice cooling, DIEA (2.46 mL, 14.1 mmol) was added to the solution. The mixture was stirred at 125° C. for 5 hours. Under ice cooling, water was added to the reaction mixture. Water was added to the reaction mixture in an ice bath. The mixture was extracted with ethyl acetate. The organic layer was washed by brine, and dried over sodium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by silica-gel column chromatography (chloroform) to give the compound 55 (2.42 g, yield 87%).

(893) .sup.1H-NMR (CDCl.sub.3) δ: 4.58 (s, 2H), 8.61 (s, 1H).

(894) Step 2

(895) The compound 55 (2.42 g, 12.3 mmol) was dissolved in methanol (24.2 mL). Under ice cooling, NaOMe (28% MeOH solution, 2.37 g, 12.26 mmol) was slowly added to the solution. The mixture was stirred for 5 hours. Under ice cooling, 10% citric acid was added to the reaction mixture to render the reaction mixture acidic. The mixture was extracted with ethyl acetate. The organic layer was washed by brine, and dried over sodium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by silica-gel column chromatography (ethyl acetate-n-hexane) to give the compound 56 (1.41 g, yield 59%).

(896) Step 3

(897) The compound 56 (1.41 g, 7.110 mmol) was dissolved in tetrahydrofuran (14.1 mL). A 2 mol/L aqueous solution of sodium hydroxide (7.30 mL, 14.6 mmol) was added to the solution. The mixture was stirred for 8 hours. Under ice cooling, a 2 mol/L aqueous solution of hydrochloric acid was added to the reaction mixture to render the reaction mixture acidic. NaCl was added to the mixture until saturated. The mixture was extracted with chloroform. The organic layer was washed by brine, and dried over sodium sulfate. The solvent was evaporated under reduced pressure. The obtained solids were washed by a solvent of ethyl acetate:n-hexane=1:1 to give the compound 57 (0.75 g, yield 58%).

(898) Step 4

(899) The compound 57 (0.75 g, 4.30 mmol) was dissolved in dichloromethane (7.50 mL). DIEA (1.05 mL, 6.01 mmol) was added to the solution. The mixture was stirred for 15 hours. Water was added to the reaction mixture. The mixture was extracted with ethyl acetate. The organic layer was washed by brine, and dried over sodium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by silica-gel column chromatography (ethyl acetate-n-hexane) to give the compound 58 (0.361 mg, yield 26%).

(900) 1H-NMR (DMSO-D6) δ: 3.34 (m, 3H), 4.16 (s, 2H), 5.31 (s, 2H), 7.34 (dd, J=6.8 Hz. 2H), 7.97 (s, 1H).

(901) Step 5

(902) The compound 58 (70.0 mg, 0.22 mmol) and the compound 59 (39.0 mg, 0.286 mmol) were dissolved in dioxane (2 mL). The solution was stirred at 80° C. for 1.5 hours. Water was added to the reaction mixture. The mixture was extracted with ethyl acetate. The organic layer was washed by brine, and dried over sodium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by silica-gel column chromatography (ethyl acetate-n-hexane) to give the compound I-1138 (25.1 mg, yield 27%).

(903) .sup.1H-NMR (DMSO-D6) δ: 1.90 (s, 3H), 3.42 (s, 3H), 3.77 (s, 3H), 4.16 (s, 2H), 4.99 (s, 2H), 6.29 (s, 1H), 6.58 (d, J=8.4 Hz, 1H), 7.05 (dd, J=6.8 Hz, 2H), 7.10 (d, J=8.4 Hz, 1H), 7.26 (s, 1H), 7.58 (s, 1H).

Example 32

Synthesis of Compound I-1153

(904) ##STR00136##
Step 1

(905) The compound 60 (2.00 g, 12.4 mmol) was dissolved in ethanol (20 mL). Acetoacetic acid ethyl eater (1.60 mL, 12.4 mmol) and p-toluenesulfonic acid (0.24 g, 0.12 mmol) were added to the solution. The mixture was stirred at room temperature for 3.5 hours. The solvent was evaporated under reduced pressure. Water and the aqueous solution of sodium hydrogen carbonate were added to the residue. The mixture was extracted with ethyl acetate. The organic layer was washed by water, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The obtained light brown oil was purified by silica-gel column chromatography (hexane-ethyl acetate) to give the compound 61. (2.00 g, yield 59%).

(906) .sup.1H-NMR (CDCl.sub.3) δ: 1.27 (t, J=5.4 Hz, 3H), 1.87 (s, 3H), 4.12 (q, J=5.4 Hz, 2H), 4.36 (d, J=5.1 Hz, 2H), 4.59 (s, 1H), 6.89 (m, 2H), 8.95 (br s, 1H).

(907) Step 2

(908) The compound 61 (2.00 g, 7.32 mmol) and trimethylsilyl isothiocyanato (10.32 mL, 73.20 mmol) wore stirred at 150° C. for 1.5 hours. The reaction mixture was cooled to room temperature. Diethyl ether (10 mL) was added to the mixture. The obtained solids were filtered to give the compound 62 (1.53 g, yield 73%).

(909) .sup.1H-NMR (DMSO-D.sub.6) δ: 2.16 (s, 3H), 5.67 (s, 2H), 5.96 (s, 1H), 7.18-7.25 (m, 2H), 12.72 (s, 1H).

(910) Step 3

(911) The compound 62 (1.00 g, 3.49 mmol) was dissolved in acetonitrile (10 mL). DIEA (1.22 mL, 6.99 mmol) and methyl iodide (1.09 mL, 17.47 mmol) were added to the solution. The mixture was stirred at 50° C. for 1.5 hours. The reaction mixture was poured into ice water, and rendered the reaction mixture acidic with a 5% aqueous solution of citric acid. The mixture was extracted with ethyl acetate. The organic layer was washed by the aqueous solution of sodium hydrogen carbonato and water, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The obtained solid was solidified with hexane-ethyl acetate to give the compound 63 (0.66 g, yield 63%).

(912) .sup.1H-NMR (DMSO-D.sub.6) δ: 2.15 (s, 3H), 2.45 (s, 3H), 5.25 (s, 2H), 5.90 (s, 1H), 7.12-7.20 (m, 2H).

(913) Step 4

(914) The compound 63 (100 mg, 0.33 mmol) was dissolved in propionic acid (1 mL). 4,5-dimethoxy-2-methylaniline (223 mg, 1.33 mmol) was added to the solution. The mixture was stirred at 150° C. for 30 minutes. The reaction mixture was poured into ice water, and neutralized with the aqueous solution of sodium hydrogen carbonate. The mixture was extracted with ethyl acetate. The organic layer was washed by water and brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The obtained oil was purified by silica-gel column chromatography (hexane-ethyl acetate). The obtained residue was solidified with ethyl acetate-hexane to give the compound 5 (66 mg, yield 47%).

(915) .sup.1H-NMR (CDCl.sub.3) R: 1.91 (s, 3H), 2.20 (s, 3H), 3.81 (s, 3H), 3.85 (s, 3H), 5.24 (br s, 2H), 5.38 (s, 1H), 6.26 (s, 1H), 6.70 (s, 1H), 6.50-6.85<m, 2H), 7.52 (br s, 1H).

Example 33

Synthesis of Compound I-1248

(916) ##STR00137## ##STR00138##
Step 1

(917) The compound 67 (100 mg, 0.465 mmol) was dissolved in dichloromethane (0.5 mL). The compound 65 (0.082 mL, 0.604 mmol) and DIEA (0.105 mL, 0.604 mmol) were added to the solution. The mixture was stirred for 4 hours. Water was added to the reaction mixture. The mixture was extracted with ethyl acetate. The organic layer was washed by brine, and dried over sodium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was solidified with ethyl acetate to give the compound 68 (113 mg, yield 67%).

(918) 1H-NMR (DMSO-D6) δ: 1.40 (t, J=6.8 Hz, 3H), 2.61 (m, 3H), 4.44 (q, J=5.6, 13.6 Hz, 2H), 5.17 (s, 2H), 7.01 (dd, J=6.8 Hz, 2H), 7.27 (s, 1H).

(919) Step 2

(920) The compound 68 (150 mg, 0.415 mmol) was dissolved in acetic acid (0.75 mL). 4,5-dimethoxy-2-methylaniline (84 mg, 0.501 mmol) was added to the solution. The mixture was stirred at 100° C. for 3 hours. Water was added to the reaction mixture. The mixture was extracted with ethyl acetate. The organic layer was washed by brine, and dried over sodium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by silica-gel column chromatography (ethyl acetate-n-hexane) to give the compound I-252 (112 mg, yield 56%). 1H-NMR (DMSO-D6) δ: 1.24 (t, J=7.2 Hz, 3H), 1.98 (s, 3H), 3.69 (s, 3H), 3.74 (s, 3H), 4.26 (q, J=6.8, 14.0 Hz, 2H), 5.37 (s, 2H), 6.76 (s, 1H), 6.83 (s, 1H), 7.36 (dd, J=6.8 Hz, 2H), 9.05 (s, 1H).

(921) Step 3

(922) The compound I-1252 (200 mg, 0.418 mmol) was dissolved in tetrahydrofuran (1 mL). A 4 mol/L aqueous solution of lithium hydroxide (146 mL, 0.585 mmol) was added to the solution. The mixture was stirred for 30 minutes. The reaction mixture was washed by Diethyl ether. A 5% citric acid was added to the aqueous layer to render the aqueous layer acidic. The aqueous layer was extracted with ethyl acetate. The organic layer was washed by brine, and dried over sodium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was washed by ethyl acetate to give the compound I-1251 (169 mg, yield 89%).

(923) 1H-NMR (DMSO-D6) δ: 1.89 (s, 3H), 3.69 (s, 3H), 3.75 (s, 3H), 5.50 (s, 2H), 6.75 (s, 1H), 6.85 (s, 1H), 7.39 (dd, J=7.6 Hz, 2H), 9.41 (br, 1H), 14.9 (br, 1H).

(924) Step 4

(925) The compound I-1251 (650 mg, 1.44 mmol) was dissolved in tetrahydrofuran (6.5 mL). Triethylamine (0.30 mL, 2.17 mmol) and ethyl chloroformate (0.206 mL, 2.17 mmol) were added to the solution. The mixture was stirred at room temperature for 30 minutes. Insoluble materials were filtered off. Under ice cooling, the filtrate was added to the aqueous solution of sodium borohydride (mixture of sodium borohydride (82 rag, 2.17 mmol) and water (6.5 mL)). The mixture was stirred for 1 hour. Water was added to the reaction mixture. The mixture was extracted with ethyl acetate. The organic layer was washed by brine, and dried over sodium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by silica-gel column chromatography (ethyl acetate-n-hexane) to give the compound I-1256 (332 mg, yield 52%).

(926) 1H-NMR (DMSO-D6) δ: 1.88 (s, 3H), 3.69 (s, 3H), 3.75 (s, 3H), 4.03 (d, J=6.4 Hz, 2H), 4.98 (t, J=6.0 Hz, 1H), 5.33 (s, 2H), 6.73 (s, 1H), 6.82 (s, 1H), 7.34 (dd, 0.1=7.2 Hz, 2H), 8.74 (s, 1H).

(927) Step 5

(928) The compound I-1256 (51 mg, 0.117 mmol) was dissolved in dichloromethane (0.510 mL). N,N-diethylaminosulfur trifluoride (18.5 μL, 0.14 mmol) was added to the solution. The mixture was stirred at room temperature for 30 minutes. Under ice cooling, the saturated aqueous solution of sodium hydrogen carbonate was added to the mixture. The mixture was extracted with ethyl acetate. The organic layer was washed by brine, and dried over sodium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by silica-gel column chromatography (ethyl acetate-n-hexane) to afford the compound I-1248 (17 mg, yield 33%).

(929) 1H-NMR (DMSO-D6) δ: 1.90 (s, 3H), 3.70 (s, 3H), 3.75 (s, 3H), 5.33 (s, 2H), 6.75 (s, 1H), 6.83 (s, 1H), 7.33 (dd, J=8.0 Hz, 2H), 7.40 (s, 1H), 8.83 (s, 1H).

Example 34

Synthesis of Compound I-1204

(930) ##STR00139##
Step 1

(931) The compound 09 (300 mg, 1.91 mmol) was dissolved in DMF (6 mL). N-chlorosuccinimide (255 mg, 1.91 mmol) was added to the solution. The mixture was stirred for 3 hours. Water was added to the reaction mixture. The mixture was extracted with ethyl acetate. The organic layer was washed by brine, and dried over sodium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was solidified with ethyl acetate to give the compound 70 (321 mg, yield 87%).

(932) Step 2

(933) The compound 70 (100 mg, 0.522 mmol) was dissolved in dichloromethane (0.5 mL). The compound 65 (132 mg, 0.574 mmol) and DIEA (0.109 mL, 0.626 mmol) were added to the solution. The mixture was stirred for 3 hours. Water was added to the reaction mixture. The mixture was extracted with ethyl acetate. The organic layer was washed by brine, and dried over sodium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by silica-gel column chromatography (ethyl acetate-n-hexane) to give the compound 71 (98 mg, yield 55%).

(934) 1H-NMR (DMSO-D6) δ: 1.40 (t, J=7.2 Hz, 3H), 3.23 (q, J=7.2, 14.8 Hz, 2H), 5.07 (s, 2H), 6.99 (dd, J=6.8 Hz, 2H).

(935) Step 3

(936) The compound 71 (75 mg, 0.223 mmol) was dissolved in acetic acid (0.375 mL). 4,5-Dimethoxy-2-methylaniline (374 mg, 2.23 mmol) was added to the solution. The mixture was stirred at 100° C. for 3 hours. Water was added to the reaction mixture. The mixture was extracted with ethyl acetate. The organic layer was washed by brine, and dried over sodium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was purified by silica-gel column chromatography (ethyl acetate-n-hexane) to give the compound I-1264 (19.3 mg, yield 19%).

(937) 1H-NMR (DMSO-D6) δ: 1.92 (s, 3H), 3.68 (s, 3H), 3.74 (s, 3H), 5.31 (s, 2H), 6.74 (s, 1H), 6.81 (s, 1H), 7.36 (dd, J=7.2 Hz, 2H), 9.05 (br, 1H).

Example 35

Synthesis of Compound I-1281

(938) ##STR00140##
Step 1

(939) The compound 64 (231 mg, 1.61 mmol) was dissolved in dichloromethane (2.31 mL). The compound 65 (0.255 mL, 1.94 mmol) and DIEA (0.423 mL, 2.42 mmol) were added to the solution. The mixture was stirred for 3 hours. Water was added to the reaction mixture. The mixture was extracted with ethyl acetate. The organic layer was washed by brine, and dried over sodium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was solidified with ethyl acetate to give the compound 66 (104 mg, yield 22%).

(940) 1H-NMR (DMSO-6) δ: 2.60 fin, 3H), 5.12 (s, 2H), 7.00 (dd, J=6.8 Hz, 2H), 7.62 (s, 1H).

(941) Step 2

(942) The compound 66 (830 mg, 2.75 mmol) was dissolved in acetic acid (6.64 mL). 4,5-dimethoxy-2-methylaniline (2.30 g, 13.7 mmol) was added to the solution. The mixture was stirred at 100° C. for 3 hours. Water was added to the reaction mixture. The mixture was extracted with ethyl acetate. The organic layer was washed by brine, and dried over sodium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was solidified with ethyl acetate to give the compound I-1281 (450 mg, yield 40%).

(943) .sup.1H-NMR (DMSO-D6) δ: 1.90 (s, 3H), 3.70 (s, 3H), 3.75<s, 310, 5.33 (s, 2H), 6.75 (s, 1H), 6.83 (s, 1H), 7.33 (dd, J=8.0 Hz, 2H), 7.40 (s, 1H), 8.83 (s, 1H).

Example 36

Synthesis of Compound I-1286

(944) ##STR00141##

(945) The compound I-0937 (100 mg, 0.342 mmol) was dissolved in dioxane (2 mL). A Lawesson's reagent (180 mg, 0.444 mmol) was added to the solution. The mixture was stirred at 100° C. for 1 hour. Pyridine (541 mg, 6.85 mmol) and cyanamide (71.8 mg, 1.709 mmol) were added to the reaction mixture. The mixture was stirred at 60° C. for 1 hour. Ethyl acetate and 1 mol/L hydrochloric acid solution were added to the reaction mixture. The mixture was extracted with ethyl acetate. The organic layer was dried over sodium sulfate, and filtered. The Solvent, was evaporated under reduced pressure

(946) The obtained residue was purified by silica-gel column chromatography (ethyl acetate-n-hexane) to give the compound I-1286 (25.5 mg, yield 16%).

(947) .sup.1H-NMR (DMSO-D6) δ: 2.06 (s, 3H>, 2.77 (s, 3H), 5.26 (s, 3H), 7.41 (m, 2H), 7.75 (s, 1H), 7.91 (s, 1H), 8.19 (s, 1H), 9.16 (s, 1H).

(948) The following compounds were synthesised according to the general synthetic procedures and the procedures described in Examples. Their chemical structural formulas and physical properties (LC/MS data or NMR spectrum) are shown below.

(949) TABLE-US-00001 TABLE 1 Com- pound Retention LC/MS No. Chemical structure NMR [M + H] time (min) condition I-0001 1H-NMR (CDCl3) δ: 2.06 (s, 3H), 3.71 (s, 3H), 5.01 (s, 2H), 6.66 (d, J = 6.4 Hz, 1H), 6.80 (s, 1H), 7.04-7.15 (m, 4H), 7.32- 7.40 (m, 2H), 7.53-7.61 (br, 1H). 374 1.72 [1] I-0002 1H-NMR (CDCl3) δ: 2.05 (s, 3H), 3.73 (s, 3H), 5.01 (s, 2H), 6.65 (m, 1H), 6.75-6.95 (m, 4H), 7.05-7.15 (m, 2H), 7.59 (s, 1H) 392 1.77 [1] I-0003 1H-NMR (DMSO-D6) δ: 3.59 (s, 3H), 4.94 (s, 4H), 5.20 (s, 2H), 7.01-7.03 (m, 3H), 7.11 (s, 1H), 7.24 (t, J = 9.0 Hz, 1H), 7.34 (s, 1H), 8.36 (s, 1H). 400 1.44 [3] I-0004 1H-NMR (DMSO-d6) δ: 1.90 (s, 3H), 3.61 (s, 3H), 5.14 (brs, 2H), 6.90-7.60 (m, 7H) 409 1.88 [1] I-0005 1H-NMR (DMSO-D6) δ: 1.95 (s, 3H), 2.77 (s, 3H), 3.60 (s, 5H), 5.20 (s, 2H), 7.37 (s, 3H), 7.48 (s, 1H), 7.58 (s, 1H), 7.74 (s, 1H), 8.49 (s, 1H). 445 1.6  [3]

(950) TABLE-US-00002 TABLE 2 I-0006 1H-NMR (DMSO-D6) δ: 1.79 (3H, s), 2.26 (3H, s), 3.60 (3H, s), 5.17 (2H, br s), 6.95- 7.55 (6H, m), 8.38 (1H, s). 422 2.07 [3] I-0007 1H-NMR (DMSO-D6) δ: 1.67 (s, 3H), 3.62 (s, 3H), 3.74 (s, 3H), 5.21 (s, 2H), 6.68 (1H, d, J = 7.8 Hz), 6.84 (1H, d, J = 8.3 Hz), 7.33-7.44 (m, 7H), 8.37 (s, 1H). 352 1.53 [3] I-0008 1H-NMR (CDCl3) δ: 3.12 (t, 2H), 2.22 (s, 3H), 3.48 (s, 3H), 4.07 (t, 2H), 6.30 (s, 1H), 6.67-6.69 (d, 2H), 7.09- 7.12 (m, 2H), 7.21-7.23 (m, 2H), 7.26-7.28 (m, 1H), 7.28- 7.35 (m, 2H), 7.53 (m, 1H) 370 1.71 [1] I-0009 0 1H-NMR (CDCl3) δ: 2.03 (s, 3H), 5.07 (s, 2H), 5.43 (d, J = 7.6 Hz, 1H), 6.68 (d, J = 6.8 Hz, 1H), 7.05-7.13 (m, 2H), 7.20 (d, J = 7.6 Hz, 1H), 7.32-7.49 (m, 6H). 326 2   [1] I-0010 1H-NMR (CDCl3) δ: 2.06 (s, 3H), 5.04 (s, 2H), 6.67 (d, J = 6.8 Hz, 1H), 7.06-7.65 (m, 9H). 344 1.72 [1] I-0011 1H-NMR (CDCl3) δ: 2.04 (s, 3H), 5.08 (s, 2H), 6.66 (d, J = 7.2 Hz, 1H), 7.05-7.14 (m, 2H), 7.30-7.44 (m, 6H), 7.57 (s, 1H) 359 1.89 [1]

(951) TABLE-US-00003 TABLE 3 I-0012 1H-NMR (CDCl3) δ: 1.86 (s, 3H), 2.04 (s, 3H), 5.05 (s, 2H), 6.67 (d, J = 6.0 Hz, 1H), 7.02-7.12 (m, 3H), 7.32-7.43 (m, 5H), 7.46-7.52 (br, 1H). 340 2.03 [1] I-0013 1H-NMR (CDCl3) δ: 2.02 (s, 3H), 5.15 (s, 2H), 6.65 (d, J = 8.0 HZ, 1H), 7.10-7.20 (m, 2H), 7.34-7.49 (m, 5H), 7.55- 7.61 (br, 1H), 7.79 (s, 1H). 351 2.11 [1] I-0014 409 1.79 [1] I-0015 1H-NMR (DMSO-D6) δ: 1.95 (3H, s), 4.80 (1H, d, J = 15.8 Hz), 5.03 (1H, d, J = 15.8 Hz), 6.82 (1H, d, J = 7.5 Hz), 7.09- 7.20 (3H, m), 7.54-7.61 (2H, m), 7.70 (1H, d, J = 7.8 Hz), 7.97 (1H, d, J = 7.8 Hz). 395 1.81 [1] I-0016 1H-NMR (DMSO-D6) δ: 1.82 (3H, s), 4.59 (2H, q, J = 9.0 Hz), 5.22 (2H, s), 7.05-7.44 (8H, m), 7.74 (1H, s), 8.73 (1H, s). 424 2.03 [1] I-0017 1H-NMR (CDCl3) δ: 1.33 (t, J = 7.2 Hz, 3H), 1.96 (s, 3H), 4.31 (q, J = 7.2 Hz, 2H), 5.16 (s, 2H), 6.64 (d, J = 7.6 Hz, 1H), 7.06-7.17 (m, 2H), 7.35-7.47 (m, 6H), 8.32 (s, 1H)

(952) TABLE-US-00004 TABLE 4 I-0018 1H-NMR (CDCl3) δ: 1.99 (s, 3H), 5.19 (s, 2H), 6.66 (d, J = 7.6 Hz, 1H), 7.10-7.21 (m, 2H), 7.35-7.49 (m, 5H), 7.55- 7.90 (br, 1H), 8.52 (s, 1H), 11.78-12.30 (br, 1H). 370 1.96 [1] I-0019 0 1H-NMR (DMSO-d6) δ: 1.40- 1.46 (2H, m), 1.78-1.83 (5H, m), 3.35-3.44 (2H, m), 3.77- 3.81 (2H, m), 3.93 (1H, m), 5.26 (2H, brs), 6.68 (1H, brs), 7.10 (2H, brs), 7.34-7.39 (5H, m), 8.59 (1H, brs), 10.43 (1H, brs). 453 2.14 [1] I-0020 1H-NMR (DMSO-d6) δ: 1.88 (s, 3H), 3.61 (s, 3H), 5.15- 5.34 (br, 2H), 6.93-7.51 (m, 8H), 7.95-8.20 (br, 1H), 8.01 (s, 1H), 8.72-9.00 (br, 1H). 399 1.83 [1] I-0021 1H-NMR (CDCl3) δ: 1.49 (1.51) (9H, s), 1.98 (1.75) (3H, s), 5.06 (5.03) (2H, s), 5.83-8.18 (10H, m). 441 2.25 [1] I-0022 1H-NMR (CDCl3) δ: 2.07 (2H, s), 3.24 (2H, brs), 5.01 (2H, s), 6.72 (2H, brs), 7.05-7.10 (2H, m), 7.34-7.42 (5H, m), 7.61 (1H, brs). 341 1.44 [1] I-0023 1H-NMR (DMSO-D6) δ: 1.17 (3H, t, J = 7.2 Hz), 1.86 (3H, s), 3.20 (2H, s), 4.05 (2H, q, J = 7.1 Hz), 5.06 (2H, br s), 6.55-7.45 (8H, m), 7.79 (1H, s), 9.93 (1H, s). 412 2.33 [3]

(953) TABLE-US-00005 TABLE 5 I-0024 1H-NMR (DMSO-D6) δ: 1.85 (3H, s), 2.32 (2H, t, J = 6.5 Hz), 3.46 (2H, q, J = 6.1 Hz), 4.58 (1H, br s), 5.05 (2H, br s), 6.55-7.70 (9H, m), 9.66 (1H, s). 370 1.87 [3] I-0025 1H-NMR (DMSO-D6) δ: 1.88 (3H, s), 3.17 (2H, s), 5.16 (2H, br s), 6.70-7.60 (8H, m), 7.83 (1H, s), 9.88 (1H, br s), 12.30 (1H, br s). 384 1.79 [1] I-0026 1H-NMR (DMSO-D6) δ: 1.87 (3H, s), 2.98 (2H, s), 5.08 (2H, s), 6.65-7.50 (10H, m), 7.69 (1H, s), 9.73 (1H, br s). 383 1.77 [3] I-0027 405 1.96 [1] I-0028 1H-NMR (DMSO-D6) δ: 1.93 (3H, s), 4.92 (2H, dd, J = 46.8, 14.9 Hz), 7.01-7.33 (13H, m), 7.61 (1H, s), 9.84 (1H, s). 402 2.73 [3] I-0029 0 1H-NMR (DMSO-d6) δ: 5.35 (s, 2H), 7.31-7.51 (m, 8H), 7.61-7.78 (m, 4H), 7.87 (d, J = 8.0 Hz, 1H), 8.34 (s, 1H). 457 2.41 [1]

(954) TABLE-US-00006 TABLE 6 I-0030 1H-NMR (CDCl3) δ: 2.04 (s, 3H), 2.83 (s, 3H), 3.35 (s, 3H), 4.65 (s, 1H), 5.30 (s, 2H), 5.87 (s, 1H), 6.95-7.05 (m, 2H), 7.46 (s, 1H), 7.76 (s, 1H) 447 1.81 [1] I-0031 1H-NMR (CDCl3) δ: 2.31 (3H, s), 5.08 (1H, s), 5.31 (2H, s), 6.08 (1H, d, J = 7.6 Hz), 6.94 (1H, s), 7.23 (3H, s), 7.62- 7.67 (2H, m), 7.73 (1H, d, J = 7.6 Hz), 7.85 (1H, d, J = 7.3 Hz) 394 2.13 [2] I-0032 393 1.99 [2] I-0033 1H-NMR (CDCl3) δ: 2.05 (s, 3H), 2.80 (s, 3H), 3.79 (s, 3H), 5.04 (s, 2H), 5.37 (s, 1H), 5.83 (s, 1H), 6.81 (s, 1H), 7.05 (m, 1H), 7.20 (dd, J = 8.5, 8.5 Hz, 1H), 7.25 (m, 1H), 7.29 (m, 1H), 7.72 (s, 1H). 444 1.47 [1] I-0034 411 2.01 [1]

(955) TABLE-US-00007 TABLE 7 I-0035 424 1.8 [1] I-0036 410 1.94 [1] I-0037 428 1.61 [1] I-0038 428 1.94 [1] I-0039 0 374 1.72 [1] I-0040 374 1.73 [1]

(956) TABLE-US-00008 TABLE 8 I-0041 362 1.73 [1] I-0042 326 1.64 [3] I-0043 371 1.8 [1] I-0044 371 1.81 [1] I-0045 371 1.81 [1] I-0046 381 1.64 [1]

(957) TABLE-US-00009 TABLE 9 I-0047 381 1.55 [1] I-0048 381 1.54 [1] I-0049 0 463 1.86 [3] I-0050 363 0.87 [3] I-0051 357 1.44 [1] I-0052 386 1.64 [1]

(958) TABLE-US-00010 TABLE 10 I-0053 386 1.62 [1] I-0054 386 1.69 [1] I-0055 340 2.09 [1] I-0056 369 2.15 [1] I-0057 338 1.51 [3] I-0058 384 1.7 [3]

(959) TABLE-US-00011 TABLE 11 I-0059 00 326 1.32 [3] I-0060 01 342 1.48 [3] I-0061 02 322 1.45 [3] I-0062 03 348 1.56 [3] I-0063 04 400 1.81 [3] I-0064 05 340 1.52 [3]

(960) TABLE-US-00012 TABLE 12 I-0065 06 390 1.75 [3] I-0066 07 428 2.11 [3] I-0067 08 365 1.06 [3] I-0068 09 336 1.59 [3] I-0069 0 365 1.2 [3] I-0070 441 1.45 [3]

(961) TABLE-US-00013 TABLE 13 I-0071 376 1.87 [3] I-0072 356 1.69 [3] I-0073 348 1.67 [3] I-0074 352 1.51 [3] I-0075 408 2.1 [1] I-0076 427 2.12 [1]

(962) TABLE-US-00014 TABLE 14 I-0077 475 1.99 [1] I-0078 397 2.22 [1] I-0079 0 350 1.61 [1] I-0080 376 1.79 [1] I-0081 392 1.67 [1] I-0082 340 1.47 [1]

(963) TABLE-US-00015 TABLE 15 I-0083 376 1.79 [1] I-0084 336 1.6 [3] I-0085 390 1.74 [1] I-0086 388 1.7 [1] I-0087 352 1.31 [1] I-0088 380 1.42 [1]

(964) TABLE-US-00016 TABLE 16 I-0089 0 376 1.71 [1] I-0090 340 1.47 [1] I-0091 387 1.7 [1] I-0092 356 1.65 [1] I-0093 388 1.6 [1] I-0094 410 1.78 [1]

(965) TABLE-US-00017 TABLE 17 I-0095 336 1.47 [1] I-0096 376 1.77 [1] I-0097 390 1.72 [1] I-0098 451 2.37 [1] I-0099 0 384 1.83 [1] I-0100 397 1.82 [1]

(966) TABLE-US-00018 TABLE 18 I-0101 414 1.78 [1] I-0102 336 1.48 [1] I-0103 348 1.41 [1] I-0104 364 1.52 [1] I-0105 340 1.72 [1] I-0106 336 1.61 [3]

(967) TABLE-US-00019 TABLE 19 I-0107 384 1.78 [1] I-0108 384 1.74 [1] I-0109 0 350 1.63 [1] I-0110 352 1.1 [1] I-0111 426 2.5 [1] I-0112 356 1.64 [1]

(968) TABLE-US-00020 TABLE 20 I-0113 352 1.44 [1] I-0114 350 1.6 [1] I-0115 372 1.51 [1] I-0116 376 1.78 [1] I-0117 361 1.3 [1] I-0118 393 1.77 [1]

(969) TABLE-US-00021 TABLE 21 I-0119 0 365 1.58 [3] I-0120 350 1.42 [3] I-0121 370 1.79 [3] I-0122 366 1.45 [3] I-0123 344 1.47 [1] I-0124 350 1.6 [1]

(970) TABLE-US-00022 TABLE 22 I-0125 390 1.81 [1] I-0126 390 1.82 [1] I-0127 390 1.82 [1] I-0128 324 1.55 [1] I-0129 0 380 1.7 [1] I-0130 352 1.53 [1]

(971) TABLE-US-00023 TABLE 23 I-0131 350 1.61 [1] I-0132 410 2.03 [1] I-0133 408 1.72 [1] I-0134 361 1.3 [1] I-0135 362 0.80 [1] I-0136 364 1.75 [1]

(972) TABLE-US-00024 TABLE 24 I-0137 370 1.86 [1] I-0138 414 1.92 [1] I-0139 0 342 1.59 [1] I-0140 342 1.6 [1] I-0141 354 1.52 [1] I-0142 384 1.9 [1]

(973) TABLE-US-00025 TABLE 25 I-0143 364 1.76 [1] I-0144 420 1.84 [1] I-0145 410 2.16 [1] I-0146 356 1.64 [1] I-0147 352 1.36 [1] I-0148 429 1.39 [1]

(974) TABLE-US-00026 TABLE 26 I-0149 0 432 2.06 [1] I-0150 380 1.57 [3] I-0151 406 2.05 [3] I-0152 372 1.71 [3] I-0153 324 1.51 [1] I-0154 410 2.09 [1]

(975) TABLE-US-00027 TABLE 27 I-0155 367 1.62 [3] I-0156 358 1.53 [3] I-0157 324 1.57 [1] I-0158 340 1.69 [1] I-0159 00 363 1.23 [1] I-0160 01 381 1.2 [1]

(976) TABLE-US-00028 TABLE 28 I-0161 02 370 1.73 [1] I-0162 03 368 1.64 [1] I-0163 04 394 1.81 [1] I-0164 05 410 1.93 [1] I-0165 06 384 1.73 [1] I-0166 07 408 1.99 [3]

(977) TABLE-US-00029 TABLE 29 I-0167 08 383 1.89 [3] I-0168 09 388 1.89 [3] I-0169 0 388 1.76 [1] I-0170 404 2.03 [3] I-0171 404 2.05 [3]

(978) TABLE-US-00030 TABLE 30 I-0172 404 2.03 [3] I-0173 362 1.78 [3] I-0174 362 1.78 [3] I-0175 370 1.75 [1] I-0176 368 1.64 [1]

(979) TABLE-US-00031 TABLE 31 I-0177 368 163 [1] I-0178 394 1.8 [1] I-0179 0 394 1.82 [1] I-0180 352 1.29 [3] I-0181 385 1.36 [3] I-0182 582 1.29 [1]

(980) TABLE-US-00032 TABLE 32 I-0183 370 1.37 [1] I-0184 476 2.05 [1] I-0185 337 1.35 [1] I-0186 382 1.93 [1] I-0187 362 1.8. [3] I-0188 320 1.46 [3]

(981) TABLE-US-00033 TABLE 33 I-0189 0 348 1.69 [3] I-0190 362 1.65 [1] I-0191 380 1.81 [1] I-0192 384 1.77 [1] I-0193 384 1.78 [1] I-0194 410 1.99 [1]

(982) TABLE-US-00034 TABLE 34 I-0195 410 1.98 [1] I-0196 392 2.22 [1] I-0197 325 1.91 [1] I-0198 415 1.54 [1] I-0199 0 337 1.8 [1] I-0200 354 1.54 [1]

(983) TABLE-US-00035 TABLE 35 I-0201 348 1.56 [1] I-0202 406 1.88 [1] I-0203 342 1.59 [1] I-0204 407 1.25 [1] I-0205 364 1.89 [1] I-0206 380 1.65 [1]

(984) TABLE-US-00036 TABLE 36 I-0207 447 1.43 [1] I-0208 416 1.46 [1] I-0209 0 388 1.41 [1] I-0210 364 1.76 [1] I-0211 364 1.76 [1]

(985) TABLE-US-00037 TABLE 37 I-0212 366 1.57 [1] I-0213 384 1.61 [1] I-0214 400 1.78 [1] I-0215 370 1.78 [1] I-0216 394 2.49 [3] I-0217 365 0.81 [1]

(986) TABLE-US-00038 TABLE 38 I-0218 363 1.86 [1] I-0219 0 447 2.02 [1] I-0220 366 1.49 [1] I-0221 362 1.36 [3] I-0222 392 1.87 [3] I-0223 358 1.73 [1]

(987) TABLE-US-00039 TABLE 39 I-0224 358 1.72 [1] I-0225 288 1.72 [1] I-0226 448 1.85 [1] I-0227 404 1.57 [1] I-0228 416 2.09 [3]

(988) TABLE-US-00040 TABLE 40 I-0229 0 434 1.61 [3] I-0230 418 1.82 [3] I-0231 432 1.98 [3] I-0232 493 1.68 [3] I-0233 370 1.4 [1]

(989) TABLE-US-00041 TABLE 41 I-0234 386 1.53 [1] I-0235 369 1.48 [1] I-0236 366 1.56 [1] I-0237 402 1.67 [1] I-0238 507 2.4 [1]

(990) TABLE-US-00042 TABLE 42 I-0239 0 387 1.71 [1] I-0240 390 1.28 [1] I-0241 458 2.13 [3] I-0242 428 2.11 [3] I-0243 402 1.93 [3]

(991) TABLE-US-00043 TABLE 43 I-0244 454 2.01 [3] I-0245 418 1.8 [3] I-0246 418 1.89 [3] I-0247 418 1.62 [3] I-0248 417 1.24 [3]

(992) TABLE-US-00044 TABLE 44 I-0249 0 384 1.53 [1] I-0250 400 1.65 [1] I-0251 384 1.59 [1] I-0252 388 1.78 [1] I-0253 384 1.59 [1]

(993) TABLE-US-00045 TABLE 45 I-0254 400 1.72 [1] I-0255 402 1.66 [1] I-0256 396 1.41 [1] I-0257 398 1.81 [3] I-0258 398 1.82 [3]

(994) TABLE-US-00046 TABLE 46 I-0259 00 414 1.94 [3] I-0260 01 416 1.88 [3] I-0261 02 384 1.63 [3] I-0262 03 384 1.63 [3] I-0263 04 400 1.76 [3]

(995) TABLE-US-00047 TABLE 47 I-0264 05 402 1.69 [3] I-0265 06 364 172 [1] I-0266 07 384 1.49 [1] I-0267 08 402 1.52 [1] I-0268 09 436 1.67 [1]

(996) TABLE-US-00048 TABLE 48 I-0269 0 414 1.54 [3] I-0270 414 1.56 [3] I-0271 430 1.68 [3] I-0272 432 1.61 [3] I-0273 448 1.72 [3]

(997) TABLE-US-00049 TABLE 49 I-0274 400 1.42 [3] I-0275 400 1.43 [3] I-0276 418 1.5 [3] I-0277 386 1.82 [3] 1-0278 366 1.4 [3]

(998) TABLE-US-00050 TABLE 50 I-0279 0 406 1.96 [3] I-0280 408 1.89 [1] I-0281 366 1.62 [1] I-0282 384 1.54 [1] I-0283 402 1.59 [1]

(999) TABLE-US-00051 TABLE 51 I-0284 453 2.29 [1] I-0285 408 1.92 [1] I-0286 392 1.77 [1] I-0287 380 1.48 [3] I-0288 398 1.52 [3]

(1000) TABLE-US-00052 TABLE 52 I-0289 0 398 1.2 [3] I-0290 414 1.66 [3] I-0291 416 1.59 [3] I-0292 432 1.7 [3] I-0293 432 1.72 [3]

(1001) TABLE-US-00053 TABLE 53 I-0294 424 2.11 [3] I-0295 424 2.04 [3] I-0296 424 2.14 [3] I-0297 424 1.92 [1] 1-0298 350 1.64 [1]

(1002) TABLE-US-00054 TABLE 54 I-0299 0 436 1.83 [1] I-0300 420 1.71 [1] I-0301 420 1.71 [1] I-0302 438 1.77 [1] I-0303 440 1.99 [1]

(1003) TABLE-US-00055 TABLE 55 1-0304 440 1.99 [1] 1-0305 440 1.97 [1] I-0306 356 1.73 [1] I-0307 354 1.81 [1] I-0308 404 1.53 [1]

(1004) TABLE-US-00056 TABLE 56 I-0309 0 422 1.58 [1] I-0310 386 1.47 [1] I-0311 392 1.71 [1] I-0312 370 1.65 [1] I-0313 445 1.52 [1]

(1005) TABLE-US-00057 TABLE 57 I-0314 402 1.8 [1] I-0315 418 1.87 [1] I-0316 436 1.97 [1] I-0317 424 2.08 [1] I-0318 354 1.59 [1]

(1006) TABLE-US-00058 TABLE 58 I-0319 0 372 1.63 [1] I-0320 380 1.66 [1] I-0321 432 1.87 [1] I-0322 370 1.67 [1] I-0323 354 1.52 [1]

(1007) TABLE-US-00059 TABLE 59 I-0324 372 1.59 [1] I-0325 388 1.7 [1] I-0326 372 1.59 [1] I-0327 372 1.61 [1] I-0328 392 1.75 [1]

(1008) TABLE-US-00060 TABLE 60 I-0329 0 392 176 [1] I-0330 397 1.84 [3] I-0331 411 1.89 [3] I-0332 354 1.65 [3] I-0333 370 1.79 [3]

(1009) TABLE-US-00061 TABLE 61 I-0334 388 1.84 [3] I-0335 400 1.87 [3] I-0336 414 1.95 [3] I-0337 427 1.72 [3] I-0338 467 1.9 [3]

(1010) TABLE-US-00062 TABLE 62 I-0339 0 453 1.9 [3] I-0340 441 1.89 [3] 1-0341 473 2.29 [3] I-0342 439 2.28 [3] I-0343 422 1.87 [3]

(1011) TABLE-US-00063 TABLE 63 I-0344 422 1.81 [1] I-0345 436 1.7 [1] I-0346 420 1.65 [1] 1-0347 409 1.85 [1] I-0348 388 1.75 [1]

(1012) TABLE-US-00064 TABLE 64 I-0349 0 406 1.78 [1] I-0350 418 1.64 [1] I-0351 400 1.61 [1] I-0352 366 1.37 [1] I-0353 418 1.59 [1]

(1013) TABLE-US-00065 TABLE 65 I-0354 1H-NMR (DMSO-D6) δ: 1.74 (s, 3H), 3.60 (s, 3H), 3.70 (s, 3H), 5.17 (s, 2H), 6.65 (s, 1H), 6.72 (d, J = 6.4 Hz, 1H), 7.06 (d, J = 8.0 Hz, 2H), 7.30-7.40 (m, 2H), 7.47 (t, J = 9.6 Hz, 1H), 7.54 (d, J = 6.8 Hz, 1H), 8.32 (s, 1H). 404 1.74 [1] I-0355 438 1.78 [1] I-0356 404 1.64 [1] I-0357 351 1.99 [1] I-0358 403 2.34 [3]

(1014) TABLE-US-00066 TABLE 66 I-0359 00 358 1.63 [3] I-0360 01 410 1.77 [1] I-0361 02 396 1.77 [3] I-0362 03 430 1.94 [3] I-0363 04 448 1.98 [3]

(1015) TABLE-US-00067 TABLE 67 I-0364 05 388 1.7 [3] I-0365 06 1H-NMR (DMSO-D6) δ: 1.84 (s, 3H), 3.60 (s, 3H), 5.17 (br s, 2H), 6.88-7.20 (m, 4H), 7.25-7.40 (m, 2H), 7.48 (m, 1H), 7.56 (m, 1H), 8.38 (br s, 1H). 440 1.92 [1] I-0366 07 368 1.57 [3] I-0367 08 386 1.61 [3] I-0368 09 402 1.75 [3]

(1016) TABLE-US-00068 TABLE 68 I-0369 0 420 1.79 [3] I-0370 384 1.68 [3] I-0371 402 1.71 [3] I-0372 1H-NMR (DMSO-D6) δ: 1.83 (s, 3H), 2.08 (s, 3H), 3.59 (s, 3H), 3.75 (s, 3H), 5.19 (s, 2H), 6.74-6.79 (m, 2H), 6.97-7.02 (m, 2H), 7.24 (m, 1H), 7.30 (s, 1H), 8.18 (s, 1H). 402 1.59 [1] I-0373 352 1.41 [1]

(1017) TABLE-US-00069 TABLE 69 I-0374 370 1.67 [1] I-0375 354 1.59 [1] I-0376 388 1.76 [1] I-0377 386 1.7 [1] I-0378 406 1.84 [1]

(1018) TABLE-US-00070 TABLE 70 I-0379 0 442 1.57 [1] I-0380 354 1.55 [1] I-0381 402 1.83 [1] I-0382 354 1.52 [1] I-0383 416 1.75 [1]

(1019) TABLE-US-00071 TABLE 71 I-0384 432 1.86 [1] I-0385 422 2.11 [3] I-0386 400 1.76 [3] I-0387 405 2.01 [1] I-0388 525 1.87 [1]

(1020) TABLE-US-00072 TABLE 72 I-0389 0 422 2.06 [1] I-0390 361 1.37 [3] I-0391 375 1.07 [1] I-0392 375 1.05 [1] I-0393 405 1.36 [1]

(1021) TABLE-US-00073 TABLE 73 I-0394 418 1.71 [3] I-0395 418 1.81 [1] I-0396 413 1.54 [3] I-0397 427 1.33 [1] I-0398 427 1.35 [1]

(1022) TABLE-US-00074 TABLE 74 I-0399 0 457 1.52 [1] I-0400 354 1.55 [1] I-0401 383 0.87 [1] I-0402 417 1.11 [1] I-0403 388 1.73 [1]

(1023) TABLE-US-00075 TABLE 75 I-0404 402 1.68 [1] I-0405 384 1.61 [1] I-0406 403 1.52 [1] I-0407 388 1.54 [1] I-0408 388 1.64 [3]

(1024) TABLE-US-00076 TABLE 76 I-0409 0 404 1.67 [1] I-0410 366 1.48 [1] I-0411 506 1.82 [1] I-0412 558 2.06 [1]

(1025) TABLE-US-00077 TABLE 77 I-0413 495 1.29 [1] I-0414 547 1.41 [1] I-0415 495 1.67 [1] I-0416 440 1.49 [1]

(1026) TABLE-US-00078 TABLE 78 I- 0417 492 1.44 [1] I- 0418 547 1.94 [1] I- 0419 0 418 1.7  [1] I- 0420 406 1.79 [1]

(1027) TABLE-US-00079 TABLE 79 I- 0421 422 1.95 [3] I- 0422 422 1.93 [3] I- 0423 390 2   [3] I- 0424 418 1.77 [1] I- 0425 388 1.81 [1]

(1028) TABLE-US-00080 TABLE 80 I- 0426 442 2.1  [3] I- 0427 404 1.72 [1] I- 0428 400 1.73 [1] I- 0429 0 368 1.7  [3] I- 0430 420 1.92 [3]

(1029) TABLE-US-00081 TABLE 81 I- 0431 393 1.47 [3] I- 0432 399 1.02 [1] I- 0433 354 1.67 [3] I- 0434 372 1.73 [3] I- 0435 388 1.74 [1]

(1030) TABLE-US-00082 TABLE 82 I- 0436 372 1.73 [3] I- 0437 390 165 [1] I- 0438 388 1.67 [3] I- 0439 0 418 1.52 [3] I- 0440 402 1.7 [3]

(1031) TABLE-US-00083 TABLE 83 I-0441 400 1.86 [3] I-0442 372 1.71 [3] I-0443 372 1.71 [3] I-0444 424 1.58 [3] I-0445 388 1.87 [3]

(1032) TABLE-US-00084 TABLE 84 I- 0446 418 1.85 [3] I- 0447 418 1.85 [3] I- 0448 414 1.48 [3] I- 0449 0 466 1.71 [3] I- 0450 354 1.62 [1] I- 0451 422 1.95 [3]

(1033) TABLE-US-00085 TABLE 85 I- 0452 406 1.85 [3] I- 0453 402 1.93 [3] I- 0454 386 1.82 [3] I- 0455 366 1.56 [1] I- 0456 400 1.73 [1]

(1034) TABLE-US-00086 TABLE 86 I- 0457 402 1.67 [1] I- 0458 402 1.67 [1] I- 0459 00 418 1.77 [1] I- 0460 01 418 1.8  [1] I- 0461 02 372 1.63 [1]

(1035) TABLE-US-00087 TABLE 87 I- 0462 03 388 1.75 [1] I- 0463 04 372 1.66 [1] I- 0464 05 386 1.57 [1] I- 0465 06 438 1.75 [1] I- 0466 07 424 2.07 [3] I- 0467 08 426 2   [3]

(1036) TABLE-US-00088 TABLE 88 I- 0468 09 442 2.12 [3] I- 0469 0 434 1.64 [3] I- 0470 426 2.03 [3] I- 0471 380 1.94 [3] I- 0472 396 2.2  [3] I- 0473 386 1.77 [3]

(1037) TABLE-US-00089 TABLE 89 I- 0474 404 1.8  [3] I- 0475 404 1.8  [3] I- 0476 386 1.75 [3] I- 0477 388 1.67 [3] I- 0478 404 1.79 [3]

(1038) TABLE-US-00090 TABLE 90 I- 0479 0 422 1.92 [3] I- 0480 424 1.86 [3] I- 0481 390 1.95 [3] I- 0482 392 1.88 [3] I- 0483 408 2   [3]

(1039) TABLE-US-00091 TABLE 91 I- 0484 398 1.86 [3] I- 0485 400 1.79 [3] I- 0486 416 1.91 [3] I- 0487 395 1.59 [3] I- 0488 397 1.53 [3] I- 0489 0 413 1.64 [3]

(1040) TABLE-US-00092 TABLE 92 I- 0490 396 1.57 [3] I- 0491 398 1.49 [3] I- 0492 414 1.6  [3] I- 0493 420 1.73 [1] I- 0494 454 1.88 [1]

(1041) TABLE-US-00093 TABLE 93 1-0495 456 1.83 [1] 1-0496 456 1.83 [1] 1-0497 472 1.92 [1] 1-0498 472 1.96 [1]

(1042) TABLE-US-00094 TABLE 94 I-0499 0 366 1.5  [3] I-0500 378 1.88 [3] I-0501 430 2.04 [3] I-0502 402 1.39 [3] I-0503 390 1.79 [3]

(1043) TABLE-US-00095 TABLE 95 I-0504 424 1.86 [3] I-0505 392 1.89 [3] I-0506 388 1.83 [3] I-0507 406 1.9  [3] I-0508 406 1.92 [3]

(1044) TABLE-US-00096 TABLE 96 I-0509 0 404 1.82 [3] I-0510 422 1.88 [3] I-0511 440 1.97 [3] I-0512 422 2.04 [3] I-0513 400 1.39 [3]

(1045) TABLE-US-00097 TABLE 97 I-0514 416 1.82 [1] I-0515 432 1.92 [1] I-0516 424 1.72 [3] I-0517 402 1.72 [3] I-0518 426 2.13 [3]

(1046) TABLE-US-00098 TABLE 98 I-0519 0 443 1.47 [3] I-0520 388 1.81 [1] I-0521 384 1.91 [1] I-0522 405 1.09 [1] I-0523 426 1.41 [1]

(1047) TABLE-US-00099 TABLE 99 I-0524 457 1.41 [1] I-0525 415 1.92 [1] I-0526 467 2.13 [1] I-0527 423 1.67 [1]

(1048) TABLE-US-00100 TABLE 100 I-0528 476 1.81 [1] I-0529 0 454 1.9  [1] I-0530 416 1.71 [1] I-0531 416 1.71 [1] I-0532 432 1.81 [1]

(1049) TABLE-US-00101 TABLE 101 I-0533 426 2.13 [3] I-0534 420 2.01 [3] I-0535 422 1.95 [3] I-0536 438 2.06 [3] I-0537 438 2.1  [3]

(1050) TABLE-US-00102 TABLE 102 I-0538 388 1.74 [3] I-0539 0 424 1.97 [3] I-0540 402 1.85 [3] I-0541 426 2.28 [3] I-0542 406 2.13 [3]

(1051) TABLE-US-00103 TABLE 103 I-0543 408 1.98 [3] I-0544 424 1.95 [3] I-0545 422 2.08 [3] I-0546 474 2.25 [3] I-0547 452 1.62 [3]

(1052) TABLE-US-00104 TABLE 104 I-0548 459 1.56 [3] I-0549 0 441 1.76 [3] I-0550 404 1.8  [3] I-0551 450 1.58 [3] I-0552 477 1.57 [3]

(1053) TABLE-US-00105 TABLE 105 I-0553 429 1.56 [3] I-0554 425 1.55 [1] I-0555 416 1.77 [1] I-0556 416 1.77 [1] I-0557 432 1.91 [1]

(1054) TABLE-US-00106 TABLE 106 I-0558 389 1.45 [1] I-0559 00 411 1.49 [3] I-0560 01 384 1.73 [3] I-0561 02 411 1.5  [3] I-0562 03 427 1.63 [3]

(1055) TABLE-US-00107 TABLE 107 I-0563 04 392 1.72 [1] I-0564 05 408 1.82 [1] I-0565 06 372 1.66 [1] I-0566 07 388 1.81 [1] I-0567 08 406 1.86 [1]

(1056) TABLE-US-00108 TABLE 108 I-0568 09 390 1.71 [1] I-0569 0 390 1.69 [1] I-0570 390 1.69 [1] I-0571 390 1.71 [1] I-0572 406 1.65 [1]

(1057) TABLE-US-00109 TABLE 109 I-0573 420 1.66 [1] I-0574 404 1.79 [1] I-0575 424 1.94 [1] I-0576 440 1.98 [3] I-0577 408 2.01 [3]

(1058) TABLE-US-00110 TABLE 110 I-0578 418 1.63 [3] I-0579 0 413 1.63 [3] I-0580 414 1.6 [3] I-0581 406 1.56 [1] I-0582 442 2.01 [1]

(1059) TABLE-US-00111 TABLE 111 I-0583 361 1.3 [1] I-0584 413 1.5 [1] I-0585 366 1.57 [1] I-0586 418 1.77 [1] I-0587 429 1.37 [3]

(1060) TABLE-US-00112 TABLE 112 I-0588 481 1.58 [3] I-0589 0 465 1.48 [3] I-0590 447 1.37 [3] I-0591 499 1.59 [3]

(1061) TABLE-US-00113 TABLE 113 I-0592 483 1.48 [3] I-0593 392 1.75 [1] I-0594 408 1.85 [1] I-0595 451 1.3 [1] I-0596 460 1.98 [1]

(1062) TABLE-US-00114 TABLE 114 I-0597 398 1.47 [3] I-0598 397 1.39 [1] I-0599 0 426 1.49 [3] I-0600 402 1.5 [3] I-0601 420 1.76 [1]

(1063) TABLE-US-00115 TABLE 115 I-0602 429 1.33 [1] I-0603 429 1.29 [1] I-0604 425 1.63 [3] I-0605 450 1.56 [3] I-0606 404 1.79 [3]

(1064) TABLE-US-00116 TABLE 116 1-0607 456 1.86 [1] 1-0608 404 1.71 [3] 1-0609 0 458 2.16 [3] 1-0610 418 1.83 [3] 1-0611 422 2.13 [3]

(1065) TABLE-US-00117 TABLE 117 I-0612 459 1.57 [3] I-0613 440 1.93 [3] I-0614 404 1.67 [3] I-0615 404 1.68 [3] I-0616 422 1.74 [3]

(1066) TABLE-US-00118 TABLE 118 I-0617 422 1.74 [3] I-0618 361 1.52 [3] I-0619 0 413 1.74 [3] I-0620 397 1.63 [3] I-0621 414 1.91 [3] I-0622 365 0.94 [1]

(1067) TABLE-US-00119 TABLE 119 I-0623 436 1.49 [1] I-0624 434 1.83 [1] I-0625 406 1.64 [1] I-0626 418 1.78 [1] I-0627 386 1.59 [1]

(1068) TABLE-US-00120 TABLE 120 I-0628 406 1.78 [1] I-0629 0 442 1.89 [1] I-0630 452 2.02 [1] I-0631 468 2.1 [1] I-0632 420 1.67 [1]

(1069) TABLE-US-00121 TABLE 121 I-0633 434 1.86 [1] I-0634 442 1.99 [1] I-0635 442 1.97 [1] I-0636 400 1.65 [1] I-0637 402 1.78 [3]

(1070) TABLE-US-00122 TABLE 122 I-0638 408 1.73 [3] I-0639 0 408 1.88 [3] I-0640 384 1.64 [3] I-0641 406 1.76 [3] I-0642 370 1.58 [3]

(1071) TABLE-US-00123 TABLE 123 I-0643 374 1.78 [3] I-0644 354 1.64 [3] I-0645 397 1.44 [1] I-0646 441 1.49 [1] I-0647 457 1.61 [1]

(1072) TABLE-US-00124 TABLE 124 I-0648 441 1.48 [1] I-0649 0 413 1.55 [1] I-0650 397 1.43 [1] I-0651 427 1.31 [1] I-0652 411 1.18 [1]

(1073) TABLE-US-00125 TABLE 125 I-0653 423 1.88 [1] I-0654 439 2.03 [1] I-0655 423 1.88 [1] I-0656 468 2.26 [1] I-0657 418 2.03 [1]

(1074) TABLE-US-00126 TABLE 126 I-0658 402 1.89 [1] I-0659 00 454 2.08 [1] I-0660 01 406 1.76 [3] I-0661 02 370 1.58 [3] I-0662 03 374 1.79 [3]

(1075) TABLE-US-00127 TABLE 127 I-0663 04 400 1.46 [3] I-0664 05 452 1.68 [3] I-0665 06 429 1.56 [3] I-0666 07 442 2.28 [3] I-0667 08 442 1.64 [3]

(1076) TABLE-US-00128 TABLE 128 I-0668 09 441 1.78 [3] I-0669 0 445 1.7  [3] I-0670 416 1.91 [3] I-0671 420 1.8  [3] I-0672 438 1.87 [3]

(1077) TABLE-US-00129 TABLE 129 I-0673 420 1.91 [1] I-0674 372 1.7  [3] I-0675 374 1.6  [3] I-0676 366 1.61 [3] I-0677 400 1.78 [3]

(1078) TABLE-US-00130 TABLE 130 I-0678 402 1.72 [3] I-0679 0 418 1.82 [3] I-0680 402 1.71 [3] I-0681 418 1.84 [3] I-0682 420 1.94 [3]

(1079) TABLE-US-00131 TABLE 131 I-0683 424 1.85 [3] I-0684 436 1.56 [3] I-0685 358 1.58 [3] I-0686 422 1.67 [1] I-0687 380 1.48 [1]

(1080) TABLE-US-00132 TABLE 132 I-0688 432 1.67 [1] I-0689 0 411 1.19 [1] I-0690 399 1.09 [3] I-0691 406 1.91 [3] I-0692 458 2.15 [3]

(1081) TABLE-US-00133 TABLE 133 I-0693 442 2.03 [3] I-0694 458 2.2  [3] I-0695 442 2.05 [3] I-0696 451 1.35 [3] I-0697 447 1.59 [1]

(1082) TABLE-US-00134 TABLE 134 I-0698 404 1.67 [1] I-0699 0 430 1.68 [3] I-0700 429 1.5  [3] I-0701 445 1.66 [3] I-0702 1H-NMR (DMSO-D6) δ: 1.31 (t, J = 5.1 Hz, 3H), 1.85 (s, 3H), 3.59 (s, 3H), 3.99 (q, J = 5.4 Hz, 2H), 5.15 (s, 2H), 6.69- 6.78 (m, 2H), 6.94 (m, 1H), 7.23-7.34 (m, 3H), 8.39 (br s, 1H). 420 1.68 [1]

(1083) TABLE-US-00135 TABLE 135 I-0703 399 1.22 [3] I-0704 422 1.78 [1] I-0705 385 1.57 [3] I-0706 401 1.78 [3] I-0707 1H-NMR (DMSO-D6) δ: 1.88 (s, 3H), 3.60 (s, 3H), 5.17 (br s, 2H), 6.88-7.40 (m, 7H), 8.35 (br s, 1H). 442 1.76 [1]

(1084) TABLE-US-00136 TABLE 136 I-0708 434 1.56 [1] I-0709 0 1H-NMR (DMSO-D6) δ: 1.72 (s, 3H), 3.59 (s, 3H), 4.20 (s, 4H), 5.18 (s, 2H), 6.55 (s, 1H), 6.66 (s, 1H), 6.99 (d, J = 6.9 Hz, 2H), 7.24 (t, J = 9.7 Hz, 1H), 7.30 (s, 1H), 8.16 (s, 1H). 416 1.38 [3] I-0710 1H-NMR (DMSO-D6) δ: 1.73 (s, 3H), 3.59 (s, 3H), 4.20 (s, 4H), 5.17 (s, 2H), 6.54 (s, 1H), 6.67 (s, 1H), 7.11 (d, J = 9.3 Hz, 1H), 7.18 (s, 1H), 7.31 (s, 1H), 7.44 (d, J = 8.4 Hz, 1H), 8.17 (s, 1H). 432 1.67 [3] I-0711 1H-NMR (CDCl3) δ: 1.97 (s, 3H), 3.69 (s, 3H), 5.04 (s, 2H), 6.51 (s, 1H), 6.81 (s, 1H), 6.90 (s, 1H), 7.37-7.39 (m, 5H), 7.52 (s, 1H). 402 1.78 [3] I-0712 408 1.75 [1]

(1085) TABLE-US-00137 TABLE 137 I-0713 380 1.59 111 I-0714 432 1.78 [1] I-0715 420 1.77 [1] I-0716 432 1.87 [1] I-0717 380 1.66 [1] I-0718 370 1.43 [1]

(1086) TABLE-US-00138 TABLE 138 I-0719 0 422 1.64 [1] I-0720 1H-NMR (CDC13) δ: 1.92 (s, 3H), 3.68 (s, 3H), 5.05 (s, 2H), 5.90 (s, 2H), 6.29 (s, 1H), 6.68 (s, 1H), 6.79 (s, 1H), 7.37-7.39 (m, 5H), 7.62 (s, 1H). 366 1.78 [3] I-0721 406 1.53 [1] I-0722 362 1.8 [3] I-0723 414 203 [3] I-0724 336 1.49 [3]

(1087) TABLE-US-00139 TABLE 139 I-0726 1H-NMR (CDCl3) δ: 3.73 (s, 3H), 4.86 (s, 2H), 6.62 (s, 1H), 6.79-6.82 (m, 4H), 6.91 (s, 1H), 8.28 (s, 1H). 438 1.9 [3] I-0727 1H-NMR (CDCl3) δ: 3.73 (s, 3H), 4.97 (s, 2H), 6.79 (s, 1H), 6.91 (s, 1H), 7.15-7.19 (m, 2H), 7.36 (d, J = 6.8 Hz, 1H), 7.45 (d, J = 7.3 Hz, 1H), 7.53 (s, 1H). 454 2 [3] I-0728 1H-NMR (CDCl3) δ: 0.99 (t, J = 7.5 Hz, 3H), 2.30 (q, J = 7.5 Hz, 2H), 3.70 (s, 3H), 5.04 (s, 2H), 6.50 (s, 1H), 6.82 (s, 1H), 6.91 (s, 1H), 7.30-7.42 (m, 5H), 7.58 (s, 1H). 416 1.91 [3] I-0729 1H-NMR (CDCl3) δ: 0.98 (t, J = 7.5 Hz, 3H), 2.27 (q, J = 7.5 Hz, 2H), 3.74 (s, 3H), 5.00 (s, 2H), 6.48 (s, 1H), 6.78 (s, 1H), 6.81 (dd, J = 8.9, 2.3 Hz, 1H), 6.87 (d, J = 5.9 Hz, 2H), 6.92 (s, 1H), 7.60 (s, 1H). 452 2.02 [3] I-0730 0 1H-NMR (CDCl3) δ: 1.00 (t, J = 7.5 Hz, 3H), 2.29 (q, J = 7.5 Hz, 2H), 3.73 (s, 3H), 4.97 (s, 2H), 6.48 (s, 1H), 6.80 (s, 1H), 6.93 (s, 1H), 7.17 (t, J = 8.5 Hz, 1H), 7.22 (dd, J = 4.4, 2.0 Hz, 1H), 7.43 (dd, J = 6.8, 1.9 Hz, 1H), 7.58 (s, 1H). 468 2.14 [3]

(1088) TABLE-US-00140 TABLE 140 I-0731 380 1.46 [3] I-0732 416 1.56 [3] I-0733 454 1.73 [3] I-0734 454 1.75 [3] I-0735 459 1.61 [3]

(1089) TABLE-US-00141 TABLE 141 I-0736 443 1.49 [3] I-0737 459 1.63 [3] I-0738 356 1.54 [1] I-0739 370 1.4  [1] I-0740 0 407 1.37 [3]

(1090) TABLE-US-00142 TABLE 142 I-0741 402 1.51 [3] I-0742 418 1.64 [3] I-0743 416 1.64 [3] I-0744 393 1.49 [3] I-0745 429 1.59 [3] I-0746 445 1.71 [3]

(1091) TABLE-US-00143 TABLE 143 I-0747 398 1.59 [3] I-0748 414 2.02 [3] I-0749 398 1.87 [3] I-0750 0 405 1.54 [3] I-0751 441 1.64 [3] I-0752 458 1.76 [3]

(1092) TABLE-US-00144 TABLE 144 I-0753 441 1.64 [3] I-0754 414 1.47 [3] I-0755 467 1.66 [3] I-0756 450 1.55 [3] I-0757 467 1.69 [3] I-0758 450 1.55 [3]

(1093) TABLE-US-00145 TABLE 145 I-0759 396 1.4  [1] I-0760 00 447 1.66 [1] I-0761 01 340 1.5  [1] I-0762 02 340 1.49 [1] I-0763 03 440 1.72 [1] I-0764 04 435 1.21 [3]

(1094) TABLE-US-00146 TABLE 146 I-0765 05 451 1.49 [3] I-0766 06 435 1.38 [3] I-0767 07 438 2.05 [3] I-0768 08 454 2.19 [3] I-0769 09 438 2.03 [3] I-0770 0 373 1.12 [3]

(1095) TABLE-US-00147 TABLE 147 I-0771 425 1.4  [3] I-0772 409 1.27 [3] I-0773 425 1.43 [3] I-0774 409 1.29 [3] I-0775 432 1.67 [3] I-0776 432 1.68 [3]

(1096) TABLE-US-00148 TABLE 148 I-0777 434 1.91 [1] I-0778 433 1.68 [3] I-0779 406 1.66 [3] I-0780 0 422 1.8  [3] I-0781 406 1.66 [3] I-0782 402 1.53 [3]

(1097) TABLE-US-00149 TABLE 149 I-0783 438 1.63 [3] I-0784 438 1.62 [3] I-0785 416 1.55 [3] I-0786 397 1.61 [3] I-0787 449 1.89 [3] I-0788 381 1.45 [3]

(1098) TABLE-US-00150 TABLE 150 I-0789 432 1.94 [1] I-0790 0 380 1.72 [1] I-0791 414 1.87 [1] I-0792 432 1.91 [1] I-0793 416 1.81 [1] I-0794 416 1.81 [1]

(1099) TABLE-US-00151 TABLE 151 I-0795 448 1.6  [1] I-0796 394 1.57 [3] I-0797 430 1.56 [3] I-0798 446 1.77 [3] I-0799 414 1.73 [3] I-0800 0 434 1.79 [1]

(1100) TABLE-US-00152 TABLE 152 I-0801 374 1.73 [1] I-0802 459 1.69 [1] I-0803 459 1.52 [1] I -0804 424 1.63 [1] I-0805 456 1.91 [1]

(1101) TABLE-US-00153 TABLE 153 I-0806 470 1.87 [1] I-0807 486 1.95 [1] I-0808 432 1.55 [1] I-0809 426 2.13 [3] I-0810 0 410 2.02 [3] I-0811 426 2.04 [3]

(1102) TABLE-US-00154 TABLE 154 I-0812 410 1.88 [3] I-0813 385 1.69 [3] I-0814 436 1.91 [3] I-0815 420 1.81 [3] I-0816 436 1.94 [3] I-0817 420 1.82 [3]

(1103) TABLE-US-00155 TABLE 155 I-0818 381 1.45 [1] I-0819 433 1.66 [1] I-0820 0 417 1.57 [1] I-0821 433 1.76 [1] I-0822 417 1.63 [1] I-0823 504 2.31 [3]

(1104) TABLE-US-00156 TABLE 156 I-0824 504 2.31 [3] I-0825 428 1.87 [3] I-0826 461 1.55 [3] I-0827 398 1.93 [3] I-0828 450 2.12 [3] I-0829 434 2.02 [3]

(1105) TABLE-US-00157 TABLE 157 I-0830 0 445 1.68 [3] I-0831 465 1.82 [3] I-0832 483 1.91 [3] I-0833 442 1.87 [3] I-0834 442 2.09 [3] I-0835 426 1.98 [3]

(1106) TABLE-US-00158 TABLE 158 I-0836 426 1.98 [3] I-0837 458 2.25 [3] I-0838 442 2.13 [3] I-0839 442 2.15 [3] I-0840 0 392 1.79 [3] I-0841 376 1.67 [3]

(1107) TABLE-US-00159 TABLE 159 I-0842 1H-NMR (DMSO-D6) δ: 1.84 (s, 3H), 3.73 (s, 3H), 5.19 (s, 2H), 6.73-6.79 (m, 2H), 6.96 (d, J = 8.4 Hz, 1H), 7.05 (d, J = 6.4 Hz, 2H), 7.25 (t, J = 9.6 Hz, 1H), 8.02 (d. J = 6.4 Hz, 1H), 8.47 (br, 1H). 376 1.66 [3] I-0843 408 1.9 [3] I-0844 392 1.78 [3] I-0845 392 1.77 [3] I-0846 426 1.84 [1]

(1108) TABLE-US-00160 TABLE 160 I-0847 426 1.7 [1] I-0848 456 1.67 [1] I-0849 429 1.99 [1] I-0850 0 413 1.87 [1] I-0851 413 1.87 [1] I-0852 445 2.19 [1]

(1109) TABLE-US-00161 TABLE 161 I-0853 429 2.05 [1] I-0854 429 2.07 [1] I-0855 379 1.5 [1] I-0856 431 1.75 [1] I-0857 415 1.63 [1] I-0858 393 1.63 [1]

(1110) TABLE-US-00162 TABLE 162 I-0859 445 1.87 [1] I-0860 000 429 1.76 [1] I-0861 001 429 1.71 [3] I-0862 002 420 1.78 [3] I-0863 003 424 1.67 [3]

(1111) TABLE-US-00163 TABLE 163 I-0864 004 416 1.65 [3] I-0865 005 400 1.52 [3] I-0866 006 418 1.62 [3] I-0867 007 429 1.7 [3] I-0868 008 438 1.77 [1]

(1112) TABLE-US-00164 TABLE 164 I-0869 009 460 2.04 [1] I-0870 010 388 1.83 [3] I-0871 011 440 2.06 [3] I-0872 012 440 2.09 [3] I-0873 013 424 1.94 [3] I-0874 014 424 1.95 [3]

(1113) TABLE-US-00165 TABLE 165 I-0875 015 402 1.95 [3] I-0876 016 454 2.16 [3] I-0877 017 454 2.16 [3] I-0878 018 438 2.05 [3] I-0879 019 438 2.06 [3] I-0880 020 389 1.25 [3]

(1114) TABLE-US-00166 TABLE 166 I-0881 021 441 1.53 [3] I-0882 022 425 1.42 [3] I-0883 023 391 1.43 [3] I-0884 024 443 1.71 [3] I-0885 025 427 1.56 [3]

(1115) TABLE-US-00167 TABLE 167 I-0886 026 374 1.73 [3] I-0887 027 426 1.99 [3] I-0888 028 379 1.88 [3] I-0889 029 430 2.1 [3] I-0890 030 414 1.84 [3] I-0891 031 430 2.12 [3]

(1116) TABLE-US-00168 TABLE 168 I-0892 032 415 1.98 [3] I-0893 033 410 1.52 [1] I-0894 034 441 1.92 [1] I-0895 035 415 1.65 [3] I-0896 036 667 1.89 [3] I-0897 037 451 1.79 [3]

(1117) TABLE-US-00169 TABLE 169 I-0898 038 433 1.7 [3] I-0899 039 469 1.89 [3] I-0900 040 400 1.41 [3] I-0901 041 389 1.22 [3] I-0902 042 441 1.48 [3]

(1118) TABLE-US-00170 TABLE 170 I-0903 043 425 1.36 [3] I-0904 044 441 1.64 [3] I-0905 045 425 1.51 [3] I-0906 046 416 1.57 [3] I-0907 047 416 1.54 [3]

(1119) TABLE-US-00171 TABLE 171 I-0908 048 450 1.61 [1] I-0909 049 462 1.71 [1] I-0910 050 1H-NMR (DMSO-D6) δ 1.87 (s, 3H), 3.59 (s, 3H), 4.94 (s, 4H), 5.16 (s, 2H), 7.02 (s, 1H), 7,11 (s, 1H), 7.30-7.32 (m, 4H), 8.35 (s, 1H). 418 1.54 [3] I-0911 051 418 1.54 [3] I-0912 052 448 1.53 [3]

(1120) TABLE-US-00172 TABLE 172 I-0913 053 414 1.63 [3] I-0914 054 430 1.75 [3] I-0915 055 400 1.75 [3] I-0916 056 416 1.86 [3] I-0917 057 432 1.73 [3] I-0918 058 384 1.8 [3]

(1121) TABLE-US-00173 TABLE 173 I-0919 059 436 2.03 [3] I-0920 060 420 1.91 [3] I-0921 061 438 2.01 [3] I-0922 062 421 2.12 [3] I-0923 063 472 2.33 [3] I-0924 064 456 2.23 [3]

(1122) TABLE-US-00174 TABLE 174 I-0925 065 474 2.32 [3] I-0926 066 354 1.56 [3] I-0927 067 407 1.79 [3] I-0928 068 390 1.67 [3] I-0929 069 408 1.77 [3] I-0930 070 444 1.61 [3]

(1123) TABLE-US-00175 TABLE 175 I-0931 071 461 1.53 [1] I-0932 072 474 1.93 [1] I-0933 073 487 1.8 [1] I-0934 074 483 1.89 [1] I-0935 075 433 1.52 [1]

(1124) TABLE-US-00176 TABLE 176 I-0936 076 406 111 [1] I-0937 077 435 1.63 [1] I-0938 078 415 1.56 [3] I-0939 079 415 1.59 [3] I-0940 080 448 1.87 [3]

(1125) TABLE-US-00177 TABLE 177 I-0941 081 413 1.6 [3] I-0942 082 444 1.92 [3] I-0943 083 424 1.63 [1] I-0944 084 403 1.47 [1] I-0945 085 365 1.42 [1] 1-0946 086 353 1.43 [1]

(1126) TABLE-US-00178 TABLE 178 I-0947 087 403 1.51 [1] I-0948 088 435 1.66 [1] I-0949 089 421 1.74 [1] I-0950 090 355 1.43 [1] I-0951 091 401 1.5 [1] I-0952 092 351 1.32 [1]

(1127) TABLE-US-00179 TABLE 179 I-0953 093 440 1.48 [1] I-0954 094 417 1.57 [1] I-0955 095 423 1.62 [1] I-0956 096 441 1.71 [1] I-0957 097 398 1.48 [1] I-0958 098 396 1.53 [1]

(1128) TABLE-US-00180 TABLE 180 I-0959 099 351 1.35 [1] I-0960 00 403 1.85 [1] I-0961 01 404 1.87 [1] I-0962 02 431 1.78 [1] I-0963 03 431 1.83 [1] I-0964 04 452 1.97 [1]

(1129) TABLE-US-00181 TABLE 181 I-0965 05 441 1.82 [1] I-0966 06 445 1.8 [1] I-0967 07 356 1.93 [1] I-0968 08 390 2.11 [1] I-0969 09 390 2.32 [3] I-0970 0 320 1.77 [3]

(1130) TABLE-US-00182 TABLE 182 I-0971 408 2.37 [3] I-0972 384 1.96 [3] I-0973 392 2.23 [3] I-0974 424 2.4 [3] I-0975 424 2.41 [3] I-0976 440 2.45 [3]

(1131) TABLE-US-00183 TABLE 183 I-0977 440 2.47 [3] I-0978 424 2.52 [3] I-0979 422 2.3 [3] I-0980 0 422 2.28 [3] I-0981 370 2.24 [3] I-0982 322 1.74 [3]

(1132) TABLE-US-00184 TABLE 184 I-0983 336 1.89 [3] I-0984 338 1.96 [3] I-0985 418 2.01 [1] I-0986 456 1.95 [3] I-0987 445 1.87 [1] 1-0988 458 1.63 [1] 1-0989 413 1.8 [3]

(1133) TABLE-US-00185 TABLE 185 I-0990 0 356 1.94 [1] I-0991 420 2.01 [1] I-0993 410 1.78 [1] I-0994 412 1.78 [3] I-0995 391 1.4 [3] I-0996 390 1.63 [3]

(1134) TABLE-US-00186 TABLE 186 I-0997 416 1.97 [3] I-0998 406 1.84 [1] I-0999 390 1.74 [1] I-1000 409 1.72 [1] I-1001 0 388 1.56 [3] I-1002 390 1.74 [1]

(1135) TABLE-US-00187 TABLE 187 I-1003 391 1.6 [1] I-1004 407 1.72 [1] I-1005 410 1.72 [1] I-1006 428 1.83 [1] I-1007 409 1.82 [1]

(1136) TABLE-US-00188 TABLE 188 I-1008 391 1.62 [1] I-1009 417 1.57 [3] I-1010 417 1.57 [3] I-1011 0 399 1.5 [3] I-1012 376 1.4 [3] I-1013 392 1.46 [3]

(1137) TABLE-US-00189 TABLE 189 I-1014 376 1.36 [3] I-1015 394 1.47 [3] I-1016 386 1.1 [3] I-1017 404 1.21 [3] I-1018 403 1.72 [3]

(1138) TABLE-US-00190 TABLE 190 I-1019 401 1.73 [3] I-1020 385 1.64 [3] I-1021 0 385 1.64 [3] I-1022 371 1.47 [3] I-1023 389 1.57 [3] I-1024 387 1.6 [3]

(1139) TABLE-US-00191 TABLE 191 I-1025 371 1.49 [3] I-1026 404 1.65 [3] I-1027 388 1.53 [3] I-1028 388 1.55 [3] I-1029 420 1.95 [3] I-1030 426 1.92 [3]

(1140) TABLE-US-00192 TABLE 192 I-1031 0 424 1.94 [3] I-1032 408 1.83 [3] I-1033 408 1.83 [3] I-1034 408 1.86 [3] I-1035 406 1.88 [3] I-1036 395 1.45 [1]

(1141) TABLE-US-00193 TABLE 193 I-1037 377 1.34 [1] I-1038 426 1.92 [3] I-1039 430 1.92 [3] I-1040 1H-NMR (DMSO-D6) δ: 1.87 (s, 3H), 3.73 (s, 3H), 5.14 (s, 2H), 6.74-6.79 (m, 2H), 6.98 (d, J = 8.4 Hz, 1H), 7.33 (dd, J = 8.0 Hz, 2H), 7.99 (d, J = 4.8 Hz, 1H), 8.45 (s, 1H). 394 1.62 [1] I-1041 0 1H-NMR (DMSO-D6) δ: 1.89 (s, 3H), 4.95 (s, 4H), 5.17 (s, 2H), 7.03 (s, 1H), 7.15 (s, 1H), 7.34 (t, J = 7.7 Hz, 2H), 8.02 (d, J = 5.5 Hz, 1H), 8.60 (s, 1H). 406 1.77 [3]

(1142) TABLE-US-00194 TABLE 194 I-1042 401 1.8 [3] I-1043 385 1.7 [3] I-1044 385 1.65 [3] I-1045 403 1.77 [3] I-1046 406 1.8 [3] I-1047 390 1.77 [3]

(1143) TABLE-US-00195 TABLE 195 I-1048 390 1.83 [3] I-1049 377 1.37 [1] I-1050 1H-NMR (DMSO-D6) δ: 1.77 (s, 3H), 3.77 (s, 3H), 5.20 (br s, 2H), 6.89 (m, 1H), 7.20-7.15 (m, 3H), 7.26 (m, 1H), 8.05 (m, 1H), 8.63 (br s, 1H). 394 1.61 [1] I-1051 0 410 1.72 [1] I-1052 394 1.61 [1] I-1053 459 1.93 [3]

(1144) TABLE-US-00196 TABLE 196 I-1054 417 1.75 [3] I-1055 415 1.78 [3] I-1056 399 1.68 [3] I-1057 399 1.58 [3] I-1058 412 1.7 [1] I-1059 393 1.47 [1]

(1145) TABLE-US-00197 TABLE 197 I-1060 424 1.93 [3] I-1061 00 408 1.81 [3] I-1062 01 408 1.81 [3] I-1063 02 428 1.93 [3] I-1064 03 412 1.83 [3] I-1065 04 412 1.84 [3]

(1146) TABLE-US-00198 TABLE 198 I-1066 05 1H-NMR (DMSO-D6) δ: 8.58 (1H, s), 8.03 (1H, d, J = 5.8 Hz), 7.35 (2H, t, J = 7.5 Hz), 7.10 (1H, d, J = 8.2 Hz), 6.77 (1H, d, J = 7.4 Hz), 6.69 (1H, s), 5.16 (2H, s), 3.71 (3H, s), 1.79 (3H, s). 394 1.76 [3] I-1067 06 392 1.77 [3] I-1068 07 376 1.65 [3] I-1069 08 376 1.64 [3] I-1070 09 436 2.11 [3]

(1147) TABLE-US-00199 TABLE 199 I-1071 0 418 2.19 [3] I-1072 388 1.59 [3] I-1073 404 111 [3] I-1074 373 1.23 [3] I-1075 421 1.62 [3] I-1076 421 1.61 [3]

(1148) TABLE-US-00200 TABLE 200 I-1077 437 1.74 [3] I-1078 439 1.73 [3] I-1079 460 1.78 [1] I-1080 448 2.1 [1] 1-1081 0 433 1.94 [1]

(1149) TABLE-US-00201 TABLE 201 I-1082 364 1.64 [1] I-1083 415 2.07 [1] I-1084 390 1.62 [3] I-1085 406 1.75 [3] I-1086 408 1.72 [3] I-1087 412 1.78 [3]

(1150) TABLE-US-00202 TABLE 202 I-1088 461 1.77 [1] I-1089 406 1.56 [1] I-1090 386 1.15 [3] I-1091 0 402 1.3 [3] I-1092 386 1.33 [3] I-1093 402 1.12 [3]

(1151) TABLE-US-00203 TABLE 203 I-1094 404 1.43 [3] I-1095 386 1.34 [3] I-1096 401 1.23 [3] I-1097 376 158 [1] I-1098 360 1.89 [1]

(1152) TABLE-US-00204 TABLE 204 I-1099 420 1.8 [1] I-1100 419 1.77 [1] I-1101 0 394 1.69 [3] I-1102 430 2.04 [3] I-1103 412 1.78 [3]

(1153) TABLE-US-00205 TABLE 205 I-1104 420 1.51 [1] I-1105 416 1.64 [3] I-1106 433 1.78 [3] I-1107 419 1.11 [3] I-1108 1H-NMR (DMSO-D6) δ: 1.88 (t, J = 5.9 Hz, 2H), 2.45 (s, 2H), 2.56 (s, 2H), 5.19 (s, 2H), 7.39 (d, J = 7.8 Hz, 4H), 7.82 (s, 1H), 8.05 (s, 1H), 8.75 (s, 1H) 418 1.62 [3]

(1154) TABLE-US-00206 TABLE 206 I-1109 444 2.15 [1] I-1110 408 1.53 [1] I-1111 0 390 1.46 [1] I-1112 401 1.91 [1] I-1113 434 1.99 [1]

(1155) TABLE-US-00207 TABLE 207 I-1114 398 1.52 [3] I-1115 398 1.54 [3] I-1116 414 1.64 [3] I-1117 413 1.58 [2] I-1118 1H-NMR (DMSO-D6): δ 8.82 (10.70) (1H, s), 8.09 (1H, s), 7.45 (7.11) (1H, s), 7.24 (1H, brs), 7.11 (2H, d, J = 5.0 Hz), 5.20 (2H, brs), 3.81 (3H, s), 1.90 (3H, s). 395 1.47 [2]

(1156) TABLE-US-00208 TABLE 208 I-1119 385 1.6 [2] I-1120 403 1.69 [2] I-1121 0 484 2.31 [2] I-1122 465 2.25 [2] I-1123 383 2.04 [3]

(1157) TABLE-US-00209 TABLE 209 I-1124 456 2.2 [3] I-1125 450 1.74 [3] I-1126 432 1.86 [3] I-1127 432 1.57 [1] I-1128 420 2.01 [3]

(1158) TABLE-US-00210 TABLE 210 I-1129 457 2.06 [3] I-1130 413 1.95 [3] I-1131 0 458 1.89 [3] I-1132 445 1.6 [3] I-1133 424 1.83 [1]

(1159) TABLE-US-00211 TABLE 211 I-1134 424 1.75 [1] I-1135 416 1.58 [1] I-1136 431 1.97 [1] I-1137 471 1.84 [3] 1-1138 1H-NMR (DMSO-D6) δ: 1.90 (s, 3H), 3.42 (s, 3H), 3.77 (s, 3H), 4.16 (s, 2H), 4.99 (s, 2H), 6.29 (s, 1H) 6.58 (d, J = 8.4 Hz, 1H), 7.05 (dd, J = 6.8 Hz, 2H), 7.10 (d, J = 8.4 Hz, 1H), 7.26 (s, 1H), 7.58 (s, 1H), 420 2.07 [3]

(1160) TABLE-US-00212 TABLE 212 I-1139 440 202 [1] I-1140 420 1.83 [3] I-1141 0 461 1.99 [1] I-1142 432 1.73 [1] I-1143 467 1.79 [3]

(1161) TABLE-US-00213 TABLE 213 I-1144 450 1.76 [3] I-1145 420 1.66 [3] I-1146 454 2.15 [3] I-1147 450 1.84 [1] I-1148 485 1.83 [3]

(1162) TABLE-US-00214 TABLE 214 I-1149 431 1.58 [3] I-1150 406 1.68 [3] I-1151 0 401 2.15 [3] I-1152 420 1.66 [3] I-1153 1H-NMR (CDCl3) δ: 1.91 (s, 3H), 2.20 (s, 3H), 3.81 (s, 3H), 3.85 (s, 3H), 5.24 (br s, 2H), 5.38 (s, 1H), 6.26 (s, 1H), 6.70 (s, 1H), 6.50-6.85 (m, 2H), 7.52 (br s, 1H). 420 1.76 [1]

(1163) TABLE-US-00215 TABLE 215 I-1154 390 1.69 [3] I-1155 429 1.88 [3] I-1156 434 1.97 [3] I-1157 448 1.77 [3] I-1158 415 1.81 [1]

(1164) TABLE-US-00216 TABLE 216 I-1159 404 1.66 [1] I-1160 397 1.97 [1] I-1161 00 385 1.76 [1] I-1162 01 434 1.83 [3] I-1163 02 429 1.63 [3]

(1165) TABLE-US-00217 TABLE 217 I-1164 03 381 1.46 [1] I-1165 04 399 1.55 [3] I-1166 05 404 2.09 [3] I-1167 06 390 1.82 [1] I-1168 07 381 1.45 [3] I-1169 08 385 1.49 [1]

(1166) TABLE-US-00218 TABLE 218 I-1170 09 383 1.51 [1] I-1171 0 367 1.36 [1] I-1172 399 1.79 [1] I-1173 406 1.72 [3] I-1174 410 1.77 [3]

(1167) TABLE-US-00219 TABLE 219 I-1175 428 1.87 [3] I-1176 378 1.75 [1] I-1177 394 1.4 [3] I-1178 408 1.65 [3] I-1179 438 1.76 [3]

(1168) TABLE-US-00220 TABLE 220 I-1180 408 1.77 [1] I-1181 0 382 1.76 [1] I-1182 455 1.82 [1] I-1183 419 1.57 [3] I-1184 398 1.88 [1]

(1169) TABLE-US-00221 TABLE 221 I-1185 382 1.76 [1] I-1186 414 1.82 [3] I-1187 444 1.7 [1] I-1188 376 1.75 [1] I-1189 378 1.76 [1]

(1170) TABLE-US-00222 TABLE 222 I-1190 412 2.02 [3] I-1191 0 408 1.88 [3] I-1192 398 1.87 [1] I-1193 378 1.77 [1] I-1194 378 1.78 [1]

(1171) TABLE-US-00223 TABLE 223 I-1195 393 1.91 [1] I-1196 414 1.88 [1] I-1197 408 1.8 [3] I-1198 417 1.57 [3] I-1199 435 1.71 [3]

(1172) TABLE-US-00224 TABLE 224 I-1200 392 1.87 [1] I-1201 0 422 1.92 [1] I-1202 403 1.49 [3] I-1203 421 1.59 [3] I-1204 456 1.79 [3]

(1173) TABLE-US-00225 TABLE 225 I-1205 424 1.53 [3] I-1206 394 1.95 [3] I-1207 412 2.05 [3] I-1208 396 1.86 [3] I-1209 398 1.89 [1]

(1174) TABLE-US-00226 TABLE 226 I-1210 444 1.91 [1] I-1211 0 426 1.89 [3] I-1212 456 1.7 [3] I-1213 380 1.77 [1] I-1214 389 1.7 [3]

(1175) TABLE-US-00227 TABLE 227 I-1215 412 1.84 [1] I-1216 432 1.57 [3] I-1217 428 2.01 [1] I-1218 396 1.89 [1] I-1219 398 1.89 [1]

(1176) TABLE-US-00228 TABLE 228 1-1220 438 1.67 [1] 1-1221 0 471 1.62 [3] 1-122.2 489 1.62 [3] 1-1223 408 1.87 [1] 1-1224 398 2.04 [3]

(1177) TABLE-US-00229 TABLE 229 I-1225 416 2.12 [3] I-1226 392 1.91 [1] I-1227 396 1.86 [3] I-1228 374 1.82 [1] I-1229 443 1.67 [3]

(1178) TABLE-US-00230 TABLE 230 I-1230 444 1.95 [1] I-1231 0 396 1.71 [1] I-1232 1H-NMR (DMSO-D6) δ: 2.02 (s, 3H), 2.16 (s, 3H), 5.15 (br s, 2H), 7.32-7.41 (m, 2H), 7.50 (m, 1H), 7.65 (m, 1 H), 8.04 (br s, 1H), 8.71 (br s, 1H) 445 1.92 [1] I-1233 390 1.9 [3] I-1234 427 1.84 [1]

(1179) TABLE-US-00231 TABLE 231 I- 1235 426 1.55 [1] I- 1236 394 1.38 [1] I- 1237 414 1.72 [1] I- 1238 396 1.86 [1] I- 1239 432 1.84 [1] I- 1240 378 1.62 [1]

(1180) TABLE-US-00232 TABLE 232 I-1241 0 389 1.19 [1] I-1242 407 1.28 [1] I-1243 424 1.78 [1] I-1244 396 1.89 [1] I-1245 412 1.69 [1] I-1246 407 1.59 [1]

(1181) TABLE-US-00233 TABLE 233 I-1247 407 1.56 [1] I-1248 1H-NMR (DMSO-D6) δ: 1.92 (s, 3H), 3.82 (s, 3H), 3.86 (s, 3H), 5.21 (d, J = 47.2 Hz, 2H), 5.50 (s, 2H), 6.25 (s, 1H), 6.73 (s, 1H), 7.16 (dd, J = 7.2 Hz, 2H) 7.26 (m, 1H), 7.87 (s, 1H). 439 1.81 [1] I-1249 421 2.03 [1] I-1250 421 2.01 [1] I-1251 0 1H-NMR (DMSO-D6) δ: 1.89 (s, 3H), 3.69 (s, 3H), 3.75 (s, 3H), 5.50 (s, 2H), 6.75 (s, 1H), 6.85 (s, 1H), 7.39 (dd, J = 7.6 Hz, 2H), 9.41 (br, 1H), 14.9 (br, 1H). 451 1.74 [1]

(1182) TABLE-US-00234 TABLE 234 I-1252 1H-NMR (DMSO-D6) δ: 1.24 (t, J = 7.2 Hz, 3H), 1.98 (s, 3H), 3.69 (s, 3H), 3.74 (s, 3H), 4.26 (q, J = 6.8, 14.0 Hz, 2H), 5.37 (s, 2H), 6.76 (s, 1H), 6.83 (s, 1H), 7.36 (dd, J = 6.8 Hz, 2H), 9.05 (s, 1H). 479 1.89 [1] I-1253 395 1.64 [1] I-1254 391 1.72 [1] I-1255 377 1.62 [1] I-1256 1H-NMR (DMSO-D6) δ: 1.88 (s, 3H), 3.69 (s, 3H), 3.75 (s, 3H), 4.03 (d, J = 6.4 Hz, 2H), 4.98 (t, J = 6.0 Hz, 1H), 5.33 (s, 2H), 6.73 (s, 1H), 6.82 (s, 1H), 7.34 (dd, J = 7.2 Hz, 2H), 8.74 (s, 1H). 437 1.5 [1]

(1183) TABLE-US-00235 TABLE 235 I-1257 424 1.86 [1] I-1258 411 1.76 [1] I-1259 392 1.88 [3] I-1260 414 1.88 [3] I-1261 00 1H-NMR (DMSO-D6) δ: 1.87 (s, 3H), 2.05 (s, 3H), 3.69 (s, 3H), 3.74 (s, 3H), 5.33 (s, 2H), 6.70 (s, 1H), 6.81 (s, 1H), 7.04 (d, J = 6.4 Hz, 2H), 7.23 (t, J = 8,8 Hz, 1H), 8.68 (s, 1H). 403 1.86 [3]

(1184) TABLE-US-00236 TABLE 236 I-1262 01 400 2.01 [3] I-1263 02 386 1.78 [3] I-1264 03 1H-NMR (DMSO-D6) δ: 1.92 (s, 3H), 3.68 (s, 3H), 3.74 (s, 3H), 5.31 (s, 2H), 6.74 (s, 1H), 6.81 (s, 1H), 7.36 (dd, J = 7.2 Hz, 2H), 9.05 (br, 1H). 441 2.02 [3] I-1265 04 411 2.04 [3] I-1266 05 421 1.82 [3]

(1185) TABLE-US-00237 TABLE 237 I-1267 06 432 1.9 [3] I-1268 07 375 1.85 [3] I-1269 08 375 1.89 [3] I-1270 09 375 1.83 [2] I-1271 0 360 1.7 [3] I-1272 360 1.71 [3]

(1186) TABLE-US-00238 TABLE 238 I-1273 341 1.64 [2] I-1274 341 1.64 [3] I-1275 341 1.62 [3] I-1276 323 1.6 [2] I-1277 391 1.94 [3] I-1278 411 1.95 [3]

(1187) TABLE-US-00239 TABLE 239 I-1279 411 1.85 [3] I-1280 389 1.67 [1] I-1281 0 1H-NMR (DMSO-D6) δ: 1.90 (s, 3H), 3.70 (s, 3H), 3.75 (s, 3H), 5.33 (s, 2H), 6.75 (s, 1H), 6.83 (s, 1H), 7.33 (dd, J = 8.0 Hz, 2H), 7.40 (s, 1H), 8.83 (s, 1H). 407 1.64 [1] I-1282 377 1.77 [3] I-1283 377 1.75 [1] I-1284 418 1.71 [1]

(1188) TABLE-US-00240 TABLE 240 I-1285 471 1.77 [1] I-1286 1H-NMR (DMSO-D6) δ: 2.06 (s, 3H), 2.77 (S, 3H), 5.26 (s, 3H), 7.41 (m, 2H), 7.75 (s, 1H), 7.91 (s, 1H), 8.19 (s, 1H), 9.16 (s, 1H). 459 1.86 [1] I-1287 460 1.79 [1] I-1288 448 1.87 [1] I-1289 391 1.76 [3]

(1189) TABLE-US-00241 TABLE 241 I-1290 393 1.64 [3] I-1291 0 464 1.76 [3] I-1292 407 2.01 [3] I-1293 402 2.07 [3] I-1294 376 2.61 [3]

(1190) TABLE-US-00242 TABLE 242 I-1295 1H-NMR (DMSO-d6) δ: 1.85 (s, 3H), 5.17 (s, 2H), 6.98- 7.10 (m, 2H), 7.23 (m, 1H), 7.30-7.40 (m, 2H), 7.26 (m, 1H), 8.04 (br s, 1H), 8.62 (br s, 1H). 382 1.76 [1] I-1296 1H-NMR (DMSO-d6) δ: 3.72 (s, 3H), 5.18 (s, 2H), 6.77- 6.92 ((m, 2H), 7.16 (m, 1H), 7.23-7.40 (m, 2H), 8.03 (br s, 1H), 8.34 (br s, 1H). 420 2.01 [1] I-1297 1H-NMR (DMSO-d6) δ: 1.78 (s, 3H), 3.82 (s, 3H), 5.20 (s, 2H), 6.76 (m, 1H), 6.99 (m, 1H), 7.03-7.10 (m, 2H), 7.26 (m, 1H), 8.04 (m, 1H), 8.65 (br s, 1H). 394 1.60 [1]

(1191) Biological test, examples for the compounds of the present invention are described below.

Test Example 1 Evaluation of a Human P2X7 Receptor Inhibitory Activity

(1192) Stably expressing cell line (1321N1 cell transfected with the human P2X7 receptor gene (GenBank accession number NM_002502.5 including T606C and G952A SNP)) was used. The cells were seeded in a 384-well microtiter plate at a concentration of 8000 cells/well and cultured in the medium (10% fetal bovine serum, 25 mM HEPES, 1% penicillin and streptomycin in DMEM) for one day at 37° C. under 5% carbon dioxide atmosphere. After replacing with 20 μL of the HBSS buffer (20 mM HEPES, 55.6 mM D-glucose, 1×HBSS(−), pH7.4-7.5). 16 μL of 17.3 μM Yo-Pro solution in the HBSS buffer was added. The plate was placed in high-throughput cellular screening system FLIPR TETRA (Molecullar Devices, LLC.) and 15 μL of 130 μM BzATP solution in the HBSS buffer was added. Measurement, of fluorescence intensity by FLIPR TETRA was started. After eight minutes, 15 μL of DMSO solutions containing different concentrations of the compound of the present invention as prepared by dilution with the HBSS buffer were dispensed to each well through the built-in automatic dispenser, and the measurement of fluorescence intensity was continued for 20 minutes. The maximum fluorescence intensity without the compound of the present invention is calculated as 0% inhibition and the maximum fluorescence intensity when the reference compound was added is calculated as 100% inhibition. Changing values of fluorescence intensity by the compound of the present invention were calculated by difference between maximum and minimum fluorescence intensity for 20 minutes. Inhibition ratios (%) were calculated from the following equation:

(1193) $\mathrm{Inhibitation}\mathrm{ratio}\text{:}\left[1-\frac{\left(\begin{array}{c}\mathrm{changing}\mathrm{values}\mathrm{by}a\\ \mathrm{compound}\mathrm{of}\mathrm{present}\mathrm{invention}-\\ \mathrm{changing}\mathrm{values}\mathrm{by}\\ \mathrm{reference}\mathrm{compound}\end{array}\right)}{\left(\begin{array}{c}\mathrm{changing}\mathrm{values}\mathrm{without}\\ a\mathrm{compound}\\ \mathrm{of}\mathrm{the}\mathrm{present}\mathrm{invention}-\\ \mathrm{changing}\mathrm{values}\mathrm{by}\\ \mathrm{reference}\mathrm{compound}\end{array}\right)}\right]\times 100\left(\%\right)$
IC.sub.50 was calculated using Logistic approximation.

(1194) The antagonistic activity for the human P2X7 receptor of the compounds of the present invention is shown in the following table.

(1195) TABLE-US-00243 TABLE 243 Compound IC50 No. (nM) I-0005 5 I-0006 6 I-0008 37 I-0013 39 I-0014 250 I-0019 49 I-0020 17 I-0022 17 I-0030 34 I-0033 49 I-0042 830 I-0052 130 I-0055 26 I-0062 590 I-0104 41 I-0120 670 I-0121 280 I-0149 26 I-0176 13 I-0178 21 I-0185 270 I-0186 2 I-0187 230 I-0190 71 I-0193 18 I-0195 26 I-0196 13 I-0203 18 I-0205 91 I-0207 9 I-0218 19 I-0242 12 I-0289 27 I-0294 250 I-0295 170 I-0297 250 I-0335 170 I-0336 120 I-0347 20 I-0354 3 I-0358 160 I-0365 18 I-0366 35 I-0367 13 I-0370 47 I-0372 5 I-0382 350 I-0384 10 I-0397 67 I-0405 2 I-0407 6 I-0425 19 I-0437 8 I-0452 110 I-0453 73 I-0480 4 I-0487 25 I-0520 9 I-0550 2 I-0561 19 I-0597 20 I-0618 7 I-0626 4 I-0636 50 I-0652 34 I-0670 20 I-0675 190 I-0698 100 I-0702 11 I-0703 16 I-0706 15 I-0707 14 I-0738 3 I-0742 16 I-0744 180 I-0755 12 I-0771 43 I-0774 110 I-0786 25 I-0788 12 I-0792 9 I-0817 4 I-0821 5 I-0825 9 I-0833 39 I-0836 2 I-0842 5 I-0849 3 I-0857 26 I-0858 10 I-0865 8 I-0900 12 I-0910 14 I-0912 22 I-0914 22 I-0924 17 I-0928 10 I-0935 6 I-0939 4 I-0940 240 I-0941 12 I-0942 230 I-0945 170 I-0953 25 I-0957 110 I-0961 410 I-0965 440 I-0966 480 I-0967 450 I-0985 65 I-0986 24 I-0987 110 I-0989 300 I-0990 320 I-0991 29 I-1019 4 I-1040 6 I-1041 9 I-1050 10 I-1059 11 I-1066 3 I-1071 15 I-1108 4 I-1188 4 I-1216 6 I-1232 6 I-1267 10 I-1261 16 I-1263 3 I-1281 4 I-1285 27 I-1290 21 I-1295 13 I-1296 11 I-1297 16

(1196) The antagonistic activity for the human P2X7 receptor of the other compounds of the present invention is shown in the following table. As for IC.sub.50 value, value from 0 nmol/L to below 10 nmol/L is represented as “A”, value from 10 nmol/L to below 100 nmol/L is represented as “B”, value from 100 nmol/L to below 500 nmol/L is represented as “C”, and value from 500 nmol/L to below 1 pmoi/L is represented as “D”.

(1197) TABLE-US-00244 TABLE 244 Compound No. IC50 I-0001 A I-0002 A I-0003 A I-0004 A I-0007 B I-0009 A I-0010 A I-0011 B I-0012 B I-0015 D I-0016 B I-0018 C I-0021 C I-0023 C I-0024 B I-0025 D I-0026 B I-0027 B I-0028 D I-0035 C I-0036 C I-0037 A I-0038 B I-0039 B I-0040 B I-0041 A I-0043 C I-0044 B I-0045 D I-0047 D I-0050 D I-0054 C I-0056 B I-0060 D I-0061 D I-0065 D I-0066 D I-0067 D I-0068 B I-0070 B I-0071 C I-0072 B I-0073 D I-0074 B I-0075 C I-0076 C I-0077 B I-0078 C I-0080 C I-0082 C I-0083 D I-0084 B I-0085 B I-0088 C I-0089 D I-0090 C I-0091 C I-0092 C I-0093 B I-0095 B I-0096 B I-0097 C I-0098 D I-0099 C I-0100 C I-0101 B I-0102 C I-0103 C I-0105 C I-0106 B I-0107 C I-0108 B I-0109 D I-0110 C I-0111 C I-0112 B I-0113 D I-0114 C I-0115 B I-0116 A I-0117 B I-0118 B I-0124 A I-0125 B I-0126 B I-0127 B I-0128 B I-0129 C I-0130 C I-0131 C I-0132 C I-0133 C I-0134 B I-0136 A I-0137 B I-0138 D I-0139 A I-0140 B I-0141 B I-0142 B I-0143 B I-0144 C I-0145 B I-0146 B I-0147 B I-0148 B I-0150 C I-0152 C I-0153 B I-0154 C I-0155 D I-0156 C I-0157 B I-0158 B I-0161 B I-0162 A I-0163 A I-0164 A I-0165 A I-0166 A I-0167 B I-0168 A I-0169 A I-0170 C I-0171 B I-0172 B I-0173 C I-0175 B I-0177 A I-0179 A I-0180 B I-0181 D I-0182 A I-0183 B I-0184 C I-0191 C I-0192 B I-0194 B I-0198 C I-0200 B I-0201 D I-0204 C I-0206 B I-0208 A I-0209 A I-0210 B I-0211 A I-0212 A I-0213 A I-0214 A I-0215 A I-0216 C I-0217 B I-0219 B I-0220 A I-0221 B I-0222 A I-0223 B I-0224 A I-0225 C

(1198) TABLE-US-00245 TABLE 245 Compound No. IC50 I-0226 B I-0227 B I-0228 B I-0229 A I-0230 A I-0231 A I-0232 A I-0233 A I-0234 B I-0235 B I-0236 B I-0237 A I-0238 C I-0239 C I-0240 B I-0241 B I-0243 A I-0244 A I-0245 A I-0246 A I-0247 A I-0248 B I-0249 A I-0250 A I-0251 B I-0252 A I-0253 B I-0254 B I-0255 A I-0256 A I-0257 A I-0258 A I-0259 A I-0260 A I-0261 A I-0262 A I-0263 A I-0264 A I-0265 A I-0266 A I-0267 A I-0268 A I-0269 A I-0270 A I-0271 A I-0272 A I-0273 A I-0274 A I-0275 B I-0276 B I-0277 A I-0278 A I-0279 A I-0280 B I-0281 A I-0282 A I-0283 A I-0284 D I-0285 B I-0286 B I-0287 B I-0288 B I-0290 B I-0291 B I-0292 B I-0293 B I-0296 B I-0298 B I-0299 B I-0300 A I-0301 A I-0302 A I-0303 C I-0304 D I-0306 A I-0307 A I-0308 A I-0309 A I-0310 B I-0311 C I-0312 B I-0313 B I-0314 A I-0315 A I-0316 A I-0317 C I-0318 A I-0319 A I-0320 C I-0321 B I-0322 B I-0323 A I-0324 A I-0325 A I-0326 A I-0327 B I-0328 B I-0329 B I-0330 C I-0331 C I-0332 B I-0333 B I-0334 A I-0337 C I-0338 C I-0339 C I-0340 C I-0341 C I-0342 C I-0344 C I-0345 A I-0346 A I-0348 A I-0349 A I-0350 A I-0351 A I-0352 C I-0353 B I-0355 A I-0356 C I-0357 D I-0359 D I-0360 B I-0361 A I-0362 A I-0363 A I-0364 C I-0368 B I-0369 A I-0371 A I-0374 B I-0375 B I-0376 A I-0377 A I-0378 A I-0379 A I-0380 B I-0381 A I-0383 A I-0385 B I-0386 B I-0387 B I-0388 B I-0389 A I-0390 B I-0392 B I-0393 B I-0394 A I-0395 A I-0396 A I-0398 B I-0399 A I-0400 C I-0401 B I-0402 A I-0403 B I-0404 A I-0406 A I-0408 B I-0409 B

(1199) TABLE-US-00246 TABLE 246 Compound No. IC50 I-0410 A I-0411 C I-0412 C I-0415 D I-0416 B I-0417 C I-0419 A I-0420 B I-0421 B I-0422 D I-0423 B I-0424 A I-0426 B I-0427 C I-0428 A I-0429 A I-0430 A I-0431 B I-0432 B I-0433 A I-0434 A I-0435 B I-0436 A I-0438 A I-0439 A I-0440 A I-0441 A I-0442 A I-0443 A I-0444 B I-0445 B I-0446 A I-0447 A I-0448 B I-0449 A I-0450 B I-0451 C I-0454 B I-0455 B I-0456 B I-0457 A I-0458 B I-0459 A I-0460 B I-0461 A I-0462 B I-0463 A I-0464 A I-0465 A I-0466 B I-0467 A I-0468 B I-0469 A I-0470 B I-0471 A I-0472 A I-0473 A I-0474 A I-0475 A I-0476 A I-0477 A I-0478 A I-0479 B I-0481 B I-0482 A I-0483 A I-0484 B I-0485 A I-0486 A I-0488 B I-0489 A I-0490 A I-0491 A I-0492 A I-0493 B I-0494 B I-0495 B I-0496 B I-0497 B I-0498 C I-0499 B I-0500 B I-0501 B I-0502 B I-0503 A I-0504 A I-0505 B I-0506 A I-0507 A I-0508 B I-0509 A I-0510 A I-0511 A I-0512 C I-0513 C I-0514 B I-0515 B I-0516 B I-0517 A I-0518 B I-0519 B I-0521 D I-0523 B I-0524 C I-0525 C I-0526 B I-0527 D I-0529 B I-0530 B I-0531 B I-0532 B I-0533 A I-0534 A I-0535 A I-0536 A I-0537 A I-0538 B I-0539 B I-0540 A I-0541 B I-0542 B I-0543 B I-0544 B I-0545 A I-0546 B I-0547 B I-0548 B I-0549 A I-0551 B I-0552 B I-0553 B I-0554 B I-0555 B I-0556 B I-0557 B I-0558 B I-0559 B I-0560 A I-0562 B I-0563 B I-0564 B I-0565 C I-0566 B I-0567 B I-0568 B I-0569 A I-0570 A I-0571 A I-0572 A I-0573 A I-0574 A I-0575 A I-0576 B I-0577 B I-0578 A I-0579 B I-0580 B I-0581 A I-0582 C I-0583 A

(1200) TABLE-US-00247 TABLE 247 Compound No. IC50 I-0584 A I-0585 A I-0586 A I-0587 B I-0588 A I-0589 A I-0590 B I-0591 B I-0592 B I-0593 B I-0594 B I-0595 A I-0596 B I-0598 B I-0599 B I-0600 A I-0601 A I-0602 C I-0603 B I-0604 A I-0605 B I-0606 A I-0607 A I-0608 B I-0609 C I-0610 B I-0611 B I-0612 C I-0613 B I-0614 A I-0615 A I-0616 A I-0617 A I-0619 A I-0620 A I-0621 A I-0622 B I-0623 A I-0624 A I-0625 A I-0627 B I-0628 C I-0629 B I-0630 A I-0631 B I-0632 A I-0633 A I-0634 C I-0635 B I-0637 A I-0638 A I-0639 B I-0640 B I-0641 B I-0642 A I-0643 B I-0644 B I-0645 B I-0646 B I-0647 B I-0648 B I-0649 B I-0650 B I-0651 B I-0653 A I-0654 B I-0655 B I-0656 B I-0657 B I-0658 B I-0659 B I-0660 B I-0661 A I-0662 B I-0663 B I-0664 A I-0665 A I-0666 C I-0667 B I-0668 B I-0669 B I-0671 A I-0672 A I-0673 A I-0674 B I-0676 C I-0677 B I-0678 A I-0679 A I-0680 B I-0681 B I-0682 B I-0683 A I-0684 B I-0685 B I-0686 A I-0687 B I-0688 A I-0689 B I-0690 B I-0691 C I-0692 B I-0693 B I-0694 C I-0695 B I-0696 A I-0697 A I-0699 A I-0700 A I-0701 A I-0704 A I-0705 A I-0708 A I-0709 A I-0710 B I-0711 C I-0712 A I-0713 A I-0714 A I-0715 A I-0716 A I-0717 A I-0718 B I-0719 A I-0720 B I-0721 A I-0722 B I-0723 B I-0724 C I-0725 A I-0726 C I-0727 C I-0728 C I-0729 C I-0730 B I-0731 B I-0732 B I-0733 B I-0734 B I-0735 B I-0736 B I-0737 B I-0739 B I-0740 C I-0741 B I-0743 B I-0745 C I-0746 B I-0747 B I-0748 B I-0749 B I-0750 B I-0751 A I-0752 B I-0753 A I-0754 B I-0756 B I-0757 B I-0758 B I-0759 B

(1201) TABLE-US-00248 TABLE 248 Compound No. IC50 I-0760 B I-0761 C I-0762 C I-0763 A I-0764 A I-0765 B I-0766 A I-0767 B I-0768 B I-0769 B I-0770 C I-0772 B I-0773 C I-0775 B I-0776 B I-0777 A I-0778 A I-0779 A I-0780 B I-0781 B I-0782 C I-0783 B I-0784 B I-0785 B I-0787 A I-0789 A I-0790 A I-0791 A I-0793 A I-0794 A I-0795 A I-0796 B I-0797 B I-0798 B I-0799 A I-0800 B I-0801 C I-0802 A I-0803 B I-0804 A I-0805 A I-0806 B I-0807 B I-0808 A I-0809 B I-0810 B I-0811 B I-0812 B I-0813 A I-0814 A I-0815 A I-0816 A I-0818 B I-0819 B I-0820 B I-0822 B I-0823 C I-0824 B I-0826 B I-0827 B I-0828 B I-0829 B I-0830 B I-0831 A I-0832 A I-0834 A I-0835 A I-0837 A I-0838 A I-0839 A I-0840 A I-0841 A I-0843 B I-0844 A I-0845 B I-0846 A I-0847 A I-0848 A I-0850 A I-0851 A I-0852 A I-0853 A I-0854 A I-0855 B I-0856 B I-0859 B I-0860 B I-0861 A I-0862 A I-0863 A I-0864 A I-0866 A I-0867 A I-0868 B I-0869 B I-0870 B I-0871 B I-0872 B I-0873 B I-0874 B I-0875 B I-0876 A I-0877 B I-0878 A I-0879 A I-0881 C I-0882 D I-0883 B I-0884 B I-0885 B I-0886 B I-0887 B I-0888 B I-0889 A I-0890 B I-0891 B I-0892 B I-0893 A I-0894 A I-0895 B I-0896 A I-0897 A I-0898 B I-0899 A I-0901 C I-0902 B I-0903 B I-0904 B I-0905 C I-0906 B I-0907 A I-0908 A I-0909 B I-0911 B I-0913 B I-0915 B I-0916 B I-0917 B I-0918 B I-0919 B I-0920 B I-0921 A I-0922 A I-0923 B I-0925 B I-0926 B I-0927 A I-0929 A I-0930 C I-0931 B I-0932 B I-0933 C I-0934 B I-0936 B I-0937 A I-0938 A I-0943 A I-0944 C I-0946 D I-0947 B

(1202) TABLE-US-00249 TABLE 249 Compound No. IC50 I-0948 B I-0949 C I-0950 C I-0951 C I-0952 C I-0954 B I-0955 B I-0956 C I-0958 C I-0959 D I-0964 C I-0969 D I-0971 C I-0973 C I-0981 D I-0993 A I-0994 B I-0995 B I-0996 B I-0997 B I-0998 A I-0999 A I-1000 A I-1001 A I-1002 B I-1003 A I-1004 A I-1005 A I-1006 A I-1007 A I-1008 A I-1009 A I-1010 A I-1011 A I-1012 A I-1013 A I-1014 A I-1015 A I-1016 B I-1017 B I-1018 A I-1020 A I-1021 A I-1022 A I-1023 A I-1024 A I-1025 A I-1026 A I-1027 B I-1028 A I-1030 A I-1031 A I-1032 B I-1033 A I-1034 A I-1035 B I-1036 B I-1037 B I-1038 B I-1039 B I-1042 A I-1043 A I-1044 A I-1045 A I-1046 A I-1047 B I-1048 B I-1049 B I-1051 A I-1052 A I-1053 B I-1054 A I-1055 B I-1056 B I-1057 B I-1058 A I-1060 B I-1061 B I-1062 B I-1063 B I-1064 B I-1065 B I-1067 A I-1068 A I-1069 B I-1070 B I-1072 A I-1073 A I-1074 B I-1075 A I-1076 A I-1077 A I-1078 A I-1079 B I-1080 B I-1081 B I-1082 A I-1083 A I-1084 A I-1085 A I-1086 A I-1087 A I-1088 B I-1089 A I-1090 B I-1091 B I-1092 B I-1093 B I-1094 A I-1095 B I-1096 B I-1097 B I-1098 B I-1099 B I-1100 B I-1101 B I-1102 B I-1103 B I-1104 B I-1105 A I-1107 B I-1109 A I-1110 A I-1111 A I-1112 B I-1113 A I-1114 A I-1115 A I-1116 A I-1117 B I-1118 C I-1119 A I-1120 A I-1121 C I-1122 B I-1123 C I-1124 B I-1125 B I-1126 B I-1127 B I-1128 B I-1129 B I-1130 B I-1131 B I-1132 B I-1133 B I-1134 B I-1135 B I-1136 B I-1137 B I-1138 B I-1139 B I-1140 B I-1141 B I-1142 B I-1143 B I-1144 B I-1145 B I-1146 B I-1147 B

(1203) TABLE-US-00250 TABLE 250 Compound No. IC50 I-1148 B I-1149 B I-1150 B I-1151 B I-1152 A I-1153 A I-1154 A I-1155 A I-1156 A I-1157 A I-1158 A I-1159 A I-1160 A I-1161 A I-1162 A I-1163 A I-1164 A I-1165 A I-1166 A I-1167 A I-1168 A I-1169 A I-1170 A I-1171 A I-1173 A I-1174 A I-1175 A I-1176 A I-1177 A I-1178 A I-1179 A I-1180 A I-1181 A I-1182 A I-1183 A I-1184 A I-1185 A I-1186 A I-1187 A I-1189 A I-1190 A I-1191 A I-1192 A I-1193 A I-1194 A I-1195 A I-1196 A I-1197 A I-1198 A I-1199 A I-1200 A I-1201 A I-1202 A I-1203 A I-1204 A I-1205 A I-1206 A I-1207 A I-1208 A I-1209 A I-1210 A I-1211 A I-1212 A I-1213 A I-1214 A I-1215 A I-1217 A I-1218 A I-1219 A I-1220 A I-1221 A I-1222 A I-1223 A I-1224 A I-1225 A I-1226 A I-1227 A I-1228 A I-1229 A I-1230 A I-1231 A I-1233 A I-1234 A I-1235 A I-1236 A I-1237 A I-1238 A I-1239 A I-1240 A I-1241 A I-1242 A I-1243 A I-1244 A I-1245 A I-1246 A I-1247 A I-1248 B I-1249 B I-1250 C I-1251 B I-1252 B I-1253 B I-1254 A I-1255 A I-1256 B I-1257 B I-1258 A I-1259 B I-1260 B I-1262 A I-1264 A I-1265 B I-1266 B I-1268 B I-1269 B I-1270 A I-1271 A I-1272 A I-1273 A I-1274 A I-1275 C I-1276 B I-1277 A I-1278 A I-1279 A I-1280 A I-1282 A I-1283 A I-1284 A I-1286 A I-1287 B I-1288 B I-1289 C I-1291 C I-1292 C I-1293 A I-1294 B

Test Example 2 Evaluation of the Rat P2X7 Receptor Inhibitory Activity

(1204) Stably expressing cell line (1321N1 cell transfected with the rat P2X7 receptor gene (GenBank accession number NM_019256.1 including C586T and C652A SNP)) is used. The cells are seeded in a 384-well microtiter plate at a concentration of 10000 cells/well and cultured in the medium (10% fetal bovine serum, 2 mM ClutaMax-1, 1% penicillin and streptomycin in DMEM) for one day at 37° C. under 5% carbon dioxide atmosphere. After replacing with 20 μL of the HBSS buffer (20 mM HEPES, 55.6 mM D-glucose, 1×HBSS(+), pH7.4), 15 μL of 17.3 μM Yo-Pro solution in the HBSS buffer is added. The plate is placed in high-throughput cellular screening system FLIPR TETRA (Molecular Devices, LLC.) and 15 μL of 1083 μM BzATP solution in the HBSS buffer is added. Measurement of fluorescence intensity by FLIPR TETRA is started. Eight minutes after, 15 μL of DMSO solutions containing different concentrations of the compound of the present invention as prepared by dilution with the HBSS buffer are dispensed to each well through the built-in automatic dispenser, and the measurement of fluorescence intensity is continued for 20 minutes. The maximum fluorescence intensity without the compound of the present invention is calculated as 0% inhibition and the maximum fluorescence intensity when the reference compound is added is calculated as 100% inhibition. Changing values of fluorescence intensity by the compound of the present invention are calculated by difference between maximum and minimum fluorescence intensity for 20 minutes. Inhibition ratios (%) are calculated from the following equation:

(1205) $\mathrm{Inhibitation}\mathrm{ratio}\text{:}\left[1-\frac{\left(\begin{array}{c}\mathrm{changing}\mathrm{values}\mathrm{by}a\mathrm{compound}\\ \mathrm{of}\mathrm{present}\mathrm{invention}-\\ \mathrm{changing}\mathrm{values}\mathrm{by}\\ \mathrm{reference}\mathrm{compound}\end{array}\right)}{\left(\begin{array}{c}\mathrm{changing}\mathrm{values}\mathrm{without}\\ a\mathrm{compound}\\ \mathrm{of}\mathrm{the}\mathrm{present}\mathrm{invention}-\\ \mathrm{changing}\mathrm{values}\mathrm{by}\\ \mathrm{reference}\mathrm{compound}\end{array}\right)}\right]\times 100\left(\%\right)$
IC.sub.50 is calculated using logistic approximation.

Test Example 3-1: Analgesic Effect in a Seltzer Model

(1206) Preparation of Partial Sciatic Nerve Ligation Model in Rats

(1207) Rats are anaesthetized using isoflurane/O2 inhalation anaesthesia. After induction of anesthesia, the left thigh is shaved. An incision was made in the skin just below the hip bone. The muscle was bluntly dissected to expose the sciatic nerve. About one half (½) of the sciatic nerve thickness is tightly ligated with a nylon thread and the wound is closed. The right thigh was used as a sham-operated control. The right thigh underwent an identical procedure with the left hind limb, however, the sciatic nerve was not manipulated or ligated.

(1208) Evaluation (1)

(1209) Two weeks after nerve ligation, the effect on mechanical allodynia was assessed using a series of von Frey filaments. For habituation, the rats were placed into a plastic cage on a wire mesh bottom. Von Frey filaments (0.4 to 26 g) were applied to the plantar surface of the rat hind paws from the wire mesh side, and the value of the filament pressure at which the paw was withdrawn was used as a pain threshold. The measurement of mechanical sensitivity of the right and left hind paws was performed to obtain prodose mechanical sensitivity. The rats showing the threshold change from 0.6 to 2 g (in nerve ligated side) and 8 to 1.5 g (in sham operated side) were used in the experiments. On the day before the experiment, the rata were evaluated with a series of von Frey filaments to familiarize them with the test procedure. The adopted animal was administrated with the compounds of the present invention. The compounds of the present invention were homogenized with mortar and pestle and suspended or diluted in 0.5% Methyl Cellulose to prepare 0.03-100 mg/2 mL/kg suspension and orally administered to rat using a syringe attached with a sonde. Post-dose mechanical sensitivities of the right and left hind paws were measured at approximately 1 to 7 hours after drug administration. Percent reversal of mechanical allodynia for each rat was calculated using the following formula. The analgesic effects of the compounds were compared.

(1210) $\%\mathrm{Reversal}=100\times \frac{\begin{array}{c}{\mathrm{Log}}_{10}(\mathrm{Postdose}\mathrm{mechanical}\mathrm{sensitivity}\\ \mathrm{in}\mathrm{nerve}\mathrm{ligated}\mathrm{side})-\\ {\mathrm{Log}}_{10}(\mathrm{Predose}\mathrm{mechanical}\mathrm{sensitivity}\\ \mathrm{in}\mathrm{nerve}\mathrm{ligated}\mathrm{side})\end{array}}{\begin{array}{c}{\mathrm{Log}}_{10}(\mathrm{Predose}\mathrm{mechanical}\mathrm{sensitivity}\mathrm{in}\\ \mathrm{sham}\mathrm{operated}\mathrm{side})-\\ {\mathrm{Log}}_{10}(\mathrm{Predose}\mathrm{mechanical}\mathrm{sensitivty}\\ \mathrm{in}\mathrm{nerve}\mathrm{ligated}\mathrm{side})\end{array}}$

(1211) The analgesic effects of the compounds of the present invention at 3 hours after the oral administration of 3 mg/kg in the above evaluation (1) are shown below as % reversal. Compound I-0005: 45% reversal Compound I-0006: 49% reversal Compound I-0354: 51% reversal Compound I-0372: 64% reversal Compound I-1040: 49% reversal Compound I-1295: 51% reversal Compound I-1296: 59% reversal

(1212) The analgesic effects of the compounds of the present invention at 5 hours after the oral administration of 3 mg/kg in the above evaluation (1) are shown below as % reversal. Compound I-0365: 55% reversal Compound I-0702: 58% reversal Compound I-0842: 69% reversal Compound I-0910: 45% reversal Compound I-1041: 48% reversal Compound I-1050: 46% reversal Compound I-1066: 63% reversal Compound I-1108: 42% reversal Compound I-1232: 55% reversal Compound I-1261: 54% reversal Compound I-1281: 48% reversal Compound I-1297: 49% reversal

(1213) The analgesic effects of the compounds of the present invention at 7 hours after the oral administration of 3 mg/kg in the above evaluation (1) are shown below as % reversal. Compound I-0707: 53% reversal
Evaluation (2)

(1214) Mechanical hyperalgesia is evaluated using an analgesy meter (Randall Selitto). Two weeks after nerve ligation, the paw pressure test is performed using an analgesy meter (stimulus pressure increased 16 g per second) to obtain paw withdrawal thresholds (PWT). Measurements are made on both sides of the hind paw and to obtain pre-dose PWT. The rats showing the threshold change from 60 to 90 g (in nerve ligated side) and 100 to 175 g (in sham operated side) are used in the experiments. On the day before the experiment, the rats have their hind paws set on the apparatus to familiarize them with the test procedure. The adopted animal is administrated with the compound of the present invention. The compound of the present invention are homogenized with mortar and pestle and suspended or diluted in 0.5% Methyl Cellulose to prepare 0.03-100 mg/2 mL/kg suspension and orally administered to rat using a syringe attached with a sonde. Post-dose PWT of the right and left hind paws are measured at approximately 1 to 5 hours after drug administration. Percent reversal of mechanical hyperalgesia for each rat is calculated using the following formula. The analgesic effects of the compounds are compared.

(1215) $\%\mathrm{Reversal}=100\times \frac{\begin{array}{c}\mathrm{Postdose}\mathrm{PWT}\mathrm{in}\mathrm{nerve}\mathrm{ligated}\mathrm{side}-\\ \mathrm{Predose}\mathrm{PWT}\mathrm{in}\mathrm{nerve}\mathrm{ligated}\mathrm{side}\end{array}}{\begin{array}{c}\mathrm{Predose}\mathrm{PWT}\mathrm{in}\mathrm{sham}\mathrm{operated}\mathrm{side}-\\ \mathrm{Predose}\mathrm{PWT}\mathrm{in}\mathrm{nerve}\mathrm{ligated}\mathrm{side}\end{array}}$

Test Example 3-2: Analgesic Effect in a Cauda Equina Nerve Compression Model

(1216) Preparation of Animal Model

(1217) In order to prepare animal models, an incision is made in the lumbar portions of the back of rats under anesthesia to expose the fourth, fifth, and sixth lumbar vertebras. An incision is made in the 4-5 and 5-6 lumbar vertebral joints. Silicon rubber is inserted into the fourth and sixth lumbar vertebral canals from the wounds of the vertebral joints, and indwelled. The wounds are closed.

(1218) In order to sham-operated animals, rats are operated by the above procedures except for the insertion and indwelling of silicon rubber.

(1219) Evaluation of Analgesic Effect

(1220) Two weeks after operation, the effect on mechanical allodynia is assessed using a series of von Frey filaments. For habituation, the rats are placed into a plastic cage on a wire mesh bottom. Von Frey filaments (0.4 to 26 g) were applied to the plantar surface of the vat hind paws from the wire mesh side, and the value of the filament pressure at which the paw was withdrawn was used as a pain threshold. The measurement of mechanical sensitivity of the right and left hind paws is performed to obtain predose mechanical sensitivity. The mechanical sensitivity of both hind paws is evaluated to obtain predose mechanical sensitivity in the animal models showing the threshold change from 0.4 to 1 g and a higher pain threshold. The rats showing the threshold change from 8 to 15 g (in sham-operated group) are used in the experiments. On the day before the experiment, the rats are evaluated with a series of von Frey filaments to familiarize them with the test, procedure. The adopted animal is administrated with the compounds of the present invention. The compounds of the present invention are homogenized with mortar and pestle and suspended or diluted in 0.5% Methyl Cellulose to prepare 0.03-1.00 mg/2 mL/kg suspension and orally administered to rat using a syringe attached with a sonde. Post-dose mechanical sensitivities of the right and left hind paws are measured at approximately 1 to 5 hours after drug administration. Percent reversal of mechanical allodynia for each rat is calculated using the following formula. The analgesic effects of the compounds are compared.

Test Example 3-3: Analgesic Effect in an EAE Model

(1221) Preparation of Rat Experimental Autoimmune Encephalomyelitis Model

(1222) Rats (Lewis rate, female) are anaesthetized using isoflurane. The backs at the tail bases are shaved. 1 g/L of an emulsion containing CFA (complete Freund's adjuvant) and the saline solution of MBP (myelin basic protein) mixed at 1:1 is prepared, and subcutaneously administered at 100 uL/animal to the backs at the rat tail bases for immunization. This is used as an operated group. An emulsion with CFA is prepared using MBP-free saline, and similar treatment is performed. This is used as a sham-operated group.

(1223) Evaluation

(1224) Three weeks after immunization, the effect, on mechanical allodynia is assessed using a series of von Frey filaments. For habituation, the rats are placed into a plastic cage on a wire mesh bottom. Von Frey filaments (0.4 to 26 g) were applied to the plantar surface of the rat hind paws from the wire mesh side, and the value of the filament pressure at which the paw was withdrawn was used as a pain threshold. The mechanical sensitivity of both hind paws is evaluated to obtain predose mechanical sensitivity in the animal models showing the threshold change from 4 g or less and a higher pain threshold from 0.6 to 2 g. The rata showing the threshold change from 6 to 15 g (in sham-operated group) are used in the experiments. On the day before the experiment, the rats are evaluated with a series of von Frey filaments to familiarize them with the test procedure. The adopted animal is administrated with the compounds of the present invention. The compounds of the present invention are homogenized with mortar and pestle and suspended or diluted in 0.5% Methyl Cellulose to prepare 0.03-1.00 mg/2 mL/kg suspension and orally administered to rat using a syringe attached with a sonde. Post-dose mechanical sensitivities of the hind paws are measured at approximately 1 to 5 hours after drug administration. Percent reversal of mechanical allodynia for each rat is calculated using the Following formula. The analgesic effects of the compounds are compared. % Reversal=Log.sub.10 (Postdose mechanical sensitivity in the operated group)−Log.sub.10 (Predose mechanical sensitivity in the operated group)/Log.sub.10 (Predose mechanical sensitivity in the sham-operated group)−Log.sub.10 (Predose mechanical sensitivity in the operated group)

(1225) The antagonistic activity for the P2X7 receptor of the compounds of the present invention can be also evaluated by using the method described in British Journal of Pharmacology (2013) 170 624-640.

Test Example 4: CYP Inhibition Test

(1226) Using commercially available pooled human liver microsomes, an inhibitory degree of each metabolite production amount by the compound of the present invention is assessed as marker reactions of human main five CYP isoforms (CYP1A2, 2C9, 2C19, 2D6, and 3A4), 7-ethoxyresorufin O-deethylation (CYP1A2), tolbutamide methyl-hydroxylation (CYP2C9), mephenyloin dihydroxylation (CYP2C19), dextromethorphan O-demethylation (CYP2D6), and terfenadine hydroxylation.

(1227) The reaction conditions are as follows: substrate. 0.5 μmol/L ethoxyresorufin (CYP1A2), 100 μmol/L tolbutamide (CYP2C9), 50 μmol/L S mephenitoin (CYP2C19), 5 μmol/L dextromethorphan (CYP2D6), 1 μmol/L terfenadine (CYP3A4); reaction time, 15 minutes: reaction temperature, 37° C.; enzyme, pooled human liver microsomes 0.2 mg protein/mL: concentration of the compound of the present invention, 1.0, 5.0, 10, 20 μmol/L (four points).

(1228) Each five kinds of substrates, human liver microsomes, or the compound of the present invention in 50 mmol/L Hepes buffer are added to a 96-well plate at the composition as described above, and NADPH, as a cofactor is added to initiate metabolism reactions. After the incubation at 37° C. for 15 minutes, a methanol/acetonitrile=1/1 (V/V) solution is added to stop the reaction. After the centrifugation at 3000 rpm for 15 minutes, resorufin (CYP1A2 metabolite) in the supernatant is quantified by a fluorescent multilabel counter or LC/MS/MS and hydroxytolbutamide (CYP2C9 metabolite). 4′ hydroxymephenytoin (CYP2C19 metabolite), dextromethorphan (CYP2D6 metabolite), and terfenadine alcohol metabolite (CYP3A4 metabolite) are quantified by LC/MS/MS.

(1229) The sample adding DMSO as a solvent to a reaction system instead of a solution dissolving a compound of the present invention is adopted as a control (100%). Remaining activity (%) is calculated at each concentration of the compound of the present invention compared to control, and IC.sub.50 is calculated by reverse presumption by a logistic model using a concentration and an inhibition rate.

Test Example 5-1: CYP3A4 Fluorescent MBI Test

(1230) The CYP3A4 fluorescent MBI test is a test of investigating mechanism based inhibition (MBI) potential on CYP3A4 by the enhancement of inhibitory degree of metabolic reaction caused by the compound of the present invention. The test is performed using CYP3A4 enzyme expressed in Escherichia coli, as a marker reaction in which 7-benzyloxytrifluoromothylcoumarin (7-BFC) is debenzylated to produce a metabolite, 7-hydroxytrifluoromethylooumarin (HFC) emitting fluorescent, light by CYP3A4 enzyme.

(1231) The reaction conditions are as follows: substrate, 5.6 μmol/L 7-BFC; pre-reaction time, 0 or 30 minutes; substrate reaction time, 15 minutes; reaction temperature, 25° C. (room temperature); CYP3A4 content (expressed in Escherichia coli), at pre-reaction 62.5 pmol/mL, at reaction 6.25 pmol/mL (at 1.0-fold dilution); concentrations of the compound of the present invention. 0.625, 1.25, 2.5, 5, 10, 20 μmol/L (six points).

(1232) An enzyme and a solution of the compound of the present invention in K-Pi buffer (pH 7.4) as a pre-reaction solution are added to a 96-well plate at the composition of the pre-reaction as described above. A part of pre-reaction solution is transferred to another 96-well plate, and 1/10 diluted by a K-Pi buffer containing a substrate. NADPH as a co-factor is added to initiate a reaction as a marker reaction (without preincubation). After a predetermined time of a reaction, acetonitrile/0.5 mol/L Tris (trishydroxyaminomethane)=4/1 (V/V) is added to step the reaction. In addition, NADPH is added to a remaining pre-reaction solution to initiate a pre-reaction (with preincubation). After a predetermined time of a pre-reaction, a part is transferred to another plate, and 1/10 diluted by a K-Pi buffer containing a substrate to initiate a reaction as a marker reaction. After a predetermined time of a reaction, acetonitrile/0.5 mol/L Tris (trishydroxyaminomethane)=4/1 (V/V) is added to stop the reaction. For the plate on which each marker reaction has been performed, a fluorescent value of 7-HFC which is a metabolite is measured with a fluorescent plate reader. (Ex=420 nm, Em=636 nm).

(1233) The sample adding DMSO as a solvent to reaction system instead of a solution dissolving the compound of the present invention is adopted as a control (100%). Remaining activity (%) is calculated at each concentration of the compound of the present, invention compared to a control. IC.sub.50 is calculated by reverse-presumption by a logistic model using a concentration and an inhibition rate. If a difference between IC.sub.50 values with or without preincubation is 5 μmol/L or more, this is defined as (+). If the difference is 3 μmol/L or less, this is defined as (−).

Test Example 5-2: CYP3A4(MDZ)MBI Test

(1234) CYP3A4(MDZ) MBI test is a test of investigating MBI potential on CYP3A4 by the enhancement of inhibitory degree of a metabolic reaction caused by the compound of the present invention. CYP3A4 inhibition is evaluated using pooled human liver microsomes by 1-hydroxylation reaction of midazolam (MDZ) as a marker reaction.

(1235) The reaction conditions are as follows: substrate, 10 μmol/L MDZ; pre-reaction time, 0 or 30 minutest substrate reaction time, 2 minutest reaction temperature, 37° C.: protein content of pooled human liver microsomes, at pre-reaction time 0.5 mg/mL, at reaction time 0.05 pmg/mL (at 1.0-fold dilution); concentrations of the compound of the present invention, 1, 5, 10, 20 μmol/L (four points).

(1236) Pooled human liver microsomes and a solution of the compound of the present invention in K-Pi buffer (pH 7.4) as a pre-reaction solution are added to a 96-well plate at the composition of the pre-reaction. A part of pro-reaction solution is transferred to another 96-well plate, and 1/10 diluted by K-Pi buffer containing a substrate. NADPH as a co-factor is added to initiate a reaction as a marker reaction (without preincubation). After a predetermined time of a reaction, methanol/acetonitrile=1/1 (V/V) solution is added to stop the reaction. In addition, NADPH is added to a remaining pre-reaction solution to initiate a pre-reaction (with preincubation). After a predetermined time of a pre-reaction, a part is transferred to another 96-well plate, and 1/10 diluted by K-Pi buffer containing a substrate to initiate a reaction as a marker reaction. After a predetermined time of a reaction, methanol/acetonitrile=1/1 (V/V) solution is added to atop the reaction. After centrifuged at 3000 rpm for 15 minutes. 1-hydroxymidazolam in the supernatant is quantified by LC/MS/MS.

(1237) The sample adding DMSO to a reaction system instead of a solution dissolving the compound of the present invention is adopted as a control (100%). Remaining activity (%) is calculated at each concentration of the compound of the present invention compared to control, and IC value is calculated by reverse-presumption by a logistic model using a concentration and an inhibition rate. Shifted IC value is calculated as “IC of preincubation at 0 min/IC of preincubation at 30 min”. When a shifted IC is 1.5 or more, this is defined as positive. When a shifted IC is 1.0 or less, this is defined as negative.

Test Example 6: BA Test

(1238) Materials and Methods for Experiments to Evaluate Oral Absorption

(1239) (1) Animals: The mice or rats are used (2) Breeding conditions: The mice or rats are allowed to freely take solid food and sterilized tap water. (3) Dose and grouping: orally or intravenously administered at a predetermined dose; grouping is as follows (Dose depends on the compound) Oral administration: 1˜30 mg/kg (n=2˜3) Intravenous administration: 0.5˜10 mg/kg (n=2˜3) (4) Preparation of dosing solution: for oral administration, in a solution or a suspension state; for intravenous administration, in a solubilized state (5) Administration method: in oral administration, forcedly administer into ventrical us with oral probe; in intravenous administration, administer from caudal vein with a needle-equipped syringe (6) Evaluation items: blood is collected over time, and the plasma concentration of drug is measured by LC/MS/MS (7) Statistical analysis: regarding the transition of the plasma concentration of the compound of the present invention, the area under the plasma concentration-time curve (AUC) is calculated by non-linear least squares program WinNonlin (Registered trade name), and the bioavailability (BA) is calculated from the AUCs of the oral administration group and intravenous administration group.

Test Example 7: Fluctuation Ames Test

(1240) Mutagenicity of the compound of the present invention is evaluated.

(1241) A 20 μL of freezing-stored Salmonella typhimurium (TA98 strain, TA100 strain) is inoculated on 10 mL of a liquid nutrient medium (2.5% Oxoid nutrient broth No. 2), and this is incubated at 37° C. for 10 hours under shaking. The 7.70 mL of TA98 culture medium is centrifuged (2000× g, 10 minutes) and TA98 is suspended in 7.70 mL Micro F buffer (K.sub.2HPO.sub.4: 3.5 g/L, KH.sub.2PO.sub.4: 1 g/L, (NH.sub.4).sub.2SO.sub.4: 1 g/L, trisodium citrate dehydrate: 0.25 g/L, MgSO.sub.4.7H.sub.2O: 0.1 g/L) after removing the culture medium. The TAOS suspension is mixed with 120 mL Exposure medium (Micro F buffer containing Biotin: 8 μg/mL, histidine: 0.2 μg/mL, glucose: 8 mg/mL). The 3.42 mL of TA100 culture medium strain is mixed with 130 mL Exposure medium. Each 12 μL of DMSO solution of the compound of the present invention (several stage dilution from maximum dose 50 mg/mL at 2 to 3 fold ratio), DMSO as a negative control, and 50 μg/mL of 4-nitroquinoline 1-oxide DMSO solution for the TA98 strain and 0.25 μg/mL of 2-(2-furyl)-3-(5-nitro-2-furyl)acrylamide DMSO solution for the TA100 strain in the assay without metabolic activation, 40 μg/mL of 2-aminoanthracene DMSO solution for the TA98 strain and 20 μg/mL of 2-aminoanthracene DMSO solution for the TA100 strain in the assay with metabolic activation as a positive control, and 588 μL of the test bacterial suspension (498 μL and 90 μL of S9 mixture in the case of metabolic activation assay) are mixed, and this is incubated at 37° C. for 90 minutes under shaking. A 460 μL of the mixture is mixed with 2300 μL of Indicator medium (Micro F buffer containing 8 μg/mL biotin, 0.2 μg/mL histidine, 8 mg/mL glucose, 37.5 μg/mL bromocresol purple), each 50 μL is dispensed to microplate 48 wells/dose, and this is incubated at 37° C. for 3 days. Since the wells containing the bacteria which gained growth ability by point mutation in amino acid (histidine) synthesizing enzyme gene turns from purple to yellow due to a pH change, the number of yellow wells in 48 wells is counted per dose, and is compared with the negative control group. (−) and (+) means negative and positive in mutagenicity respectively,

Test Example 8: hERG Test

(1242) For the purpose of assessing risk of an electrocardiogram QT interval prolongation of the compound of the present invention, effects of the compound of the present invention on delayed rectifier K+current (I.sub.Kr), which plays an important role in the ventricular repolarization process, is studied using CHO cells expressing human ether-a-go-go related gene (hERG) channel.

(1243) After a cell is retained at a membrane potential of −80 mV by whole cell patch clamp method using an automated patch clamp system (QPatch; Sophion Bioscience A/S) and gave a leak potential of −50 mV, I.sub.Kr induced by depolarization pulse stimulation at +20 mV for 2 seconds and, further, repolarization pulse stimulation at −50 mV for 2 seconds, is recorded. After the generated current is stabilized, extracellular solution (NaCl: 145 mmol/L, KCl: 4 mmol/L, CaCl.sub.2: 2 mmol/L, MgCl.sub.2: 1 mmol/L, glucose: 10 mmol/L, HEPES (4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid): 10 mmol/L, pH=7.4), in which the compound of the present invention had been dissolved at an objective concentration in the extracellular solution, is applied to the cell at room temperature for 10 minutes. From the recording I.sub.Kr, an absolute value of the tail peak current is measured based on the current value at the resting membrane potential using analysis software (Falstor Patch; Sophion Bioscience A/S). Further, the % inhibition of tail peak current for the compound of the present invention relative to the tail peak current after application of the vehicle (0.1% dimethyl sulfoxide solution) is calculated to assess influence of the compound of the present invention on I.sub.Kr.

Test Example 9: Solubility Test

(1244) The solubility of the compound of the present invention is determined under 1% DMSO addition conditions. 10 mmol/L solution of the compound is prepared with DMSO. 2 μL of the solution of the compound of the present invention is respectively added to 198 μL of JP-1 fluid or JP-2 fluid, or 6 μL of the solution of the compound of the present invention is respectively added to 594 μL of JP-1 fluid or JP-2 fluid. The mixture is left standing for 16 hours at 25° C. (condition 1) or shaking at room temperature for 1 hour (condition 2), and the mixture is vacuum-filtered. The filtrate is 10- or 100-fold diluted with methanol/water=1/1 (v/v) or acetonitrile/methanol/water=1/1/2 (v/v/v), and the compound concentration in the filtrate is measured with LC/MS or Solid-Phase Extraction (SPE)/MS by the absolute calibration method.

(1245) The composition of the JP-1 fluid is as below. Water is added to 2.0 g of sodium chloride and 7.0 mL of hydrochloric acid to reach 1000 mL.

(1246) The composition of the JP-2 fluid is as below. Composition 1. About 200 mL of 0.2 mol/L sodium hydroxide test, solution is added to 200 mL of 0.2 mol/L potassium dihydrogen phosphate test, solution to adjust the pH to 6.8, followed by addition of 600 mL of water. Composition 2. 3.40 g of potassium dihydrogen phosphate and 3.55 g of anhydrous disodium hydrogen phosphate are dissolved in water to reach 1000 mL. Composition 3. 1 volume of water is added to 1 volume of the solution in which 3.40 g of potassium dihydrogen phosphate and 3.55 g of anhydrous disodium hydrogen phosphate are dissolved in water to reach 1000 mL.

Test Example 10: Metabolism Stability Test

(1247) Using commercially available pooled human liver microsomes, the compound of the present invention is reacted for a constant time, a remaining rate is calculated by comparing a reacted sample and an unreacted sample, thereby, a degree of metabolism in liver is assessed.

(1248) A reaction is performed (oxidative reaction) at 37° C. for 0 minute or 30 minutes in the presence of 1 mmol/L NADPH in 0.2 mL of a buffer (50 mmol/L Tris-HCl pH 7.4, 150 mmol/L potassium chloride, 10 mmol/L magnesium chloride) containing 0.5 mg protein/mL of human liver microsomes. After the reaction. 50 μL of the reaction solution is added to 100 μL of a methanol/acetonitrile=1/1 (v/v), mixed and centrifuged at 0.3000 rpm for 15 minutes. The compound of the present invention in the supernatant is quantified by LC/MS/MS or Solid-Phase Extraction (SPE)/MS, and a remaining amount of the compound of the present invention after the reaction is calculated, letting a compound amount at 0 minute reaction time to be 100%.

Test Example 11: Powder Solubility Test

(1249) Appropriate quantity of the compound of the present invention is put in suitable containers. 200 μL of JP-1 fluid (water is added to 2.0 g of sodium chloride and 7.0 mL of hydrochloric acid to reach 1000 mL), 200 μL of JP-2 fluid (1 volume of water is added to 1 volume of the solution which 3.40 g of potassium dihydrogen phosphate and 3.55 g of anhydrous disodium hydrogen phosphate dissolve in water to reach 1000 mL) or 20 mmol/L sodium taurocholate (TCA)/JP-2 fluid (JP-2 fluid is added to 1.08 g of TCA to reach 100 mL) is independently added to each container. When total amount is dissolved after adding the test reagent, the compound of the present invention is added appropriately. After sealing and shaking at 37° C. for 1 hour, solution is filtrated and 100 μL of methanol is added to 100 μL of each filtrate to dilute two-fold. The dilution rate is changed as necessary. After checking that there is no bubble and precipitate, the container is sealed and shaken. The compound of the present invention is measured using HPLC by absolute calibration curve method.

Test Example 12: Brain Distribution Test

(1250) The compound according to the present invention is intravenous administered at a dose of 0.5 mg/mL/kg to rats. After 30 minutes, the rats are killed by exsanguination through whole blood collection from the inferior vena cava under isoflurane anesthesia.

(1251) Then, the brain is excised, and 20 to 25% homogenate is prepared with distilled water.

(1252) The obtained blood is centrifuged, and plasma is then obtained. Then, control plasma and control brain are added to the brain sample and the plasma sample, respectively, at 1:1, and each sample is assayed using LC/MS/MS. The measured area ratio (blain/plasma) obtained is used as a brain Kp value.

Test Example 13: P-gp Substrate Test

(1253) The compound according to the present invention is added to one side of Transwell (registered trademark. CORNING) where human MDR1-expressing cells or parent cells have been monolayer-cultured. The cells are reacted for a constant time. The membrane permeability coefficients from the apical side toward the basolateral side (A.fwdarw.B) and from the basolateral side toward the apical side (B.fwdarw.A) are calculated for the MDR1-expressing cells or the parent cells, and the efflux ratio (ER: ratio of the membrane permeability coefficients of B.fwdarw.A and A.fwdarw.B) values of the MDR1-expressing cells and the parent cells are calculated. The efflux ratio (ER) values of the MDR1-expressing cells and the parent cells are compared to confirm whether or not the compound of the present invention would be a P-gp substrate.

Test Example 14: mdr1a (−/−) B6 Mouse P-Gp Substrate Test

(1254) Animal Used

(1255) mdr1a (−/−) B6 mice (knockout mice) or C57BL/6J mice (wild mice)

(1256) Method

(1257) 1. The mice are allowed to freely take solid food and sterilized tap water. 2. The compound of the present invention is administered to 3 animals at each point in time. Blood and brain samples are collected at a predetermined point, in time (e.g., 15 minutes, 30 minutes, 1 hour, 2 hours, 4 hours, 6 hours, 8 hours or 24 hours) after administration. The blood (0.3-0.7 mL) is collected with a syringe containing anticoagulants (EDTA and heparin). The blood and brain samples are immediately cooled in ice. 3. The blood sample is centrifugated (1780× g, 10 minutes) for removal of cells to obtain plasma. Then, the plasma sample is transferred to a tube, and stored at −70° C. 4. The brain sample is homogenized at a tissue weight:distilled water weight ratio=1:3, transferred to a tube, and stored at −70® C. 5. The plasma and brain samples are deproteinized, and analyzed by LC/MS/MS. A calibration curve prepared from blank plasma or blank brain is used in measurement. A sample for quality control is used to confirm measurement trueness and accuracy. 6. Concentrations (ng/mL and ng/g) in the plasma and the brain are analyzed by an appropriate method for determining pharmacokinetic parameters, for example, WinNonlin (registered trademark) pharmacokinetic analysis software program.
Analysis
Kp: Brain/Blood Concentration Ratio
Kp ratio=knockout mouse(KO)Kp value/wild mouse(Wild)Kp value
KO/Wild ratio of brain AUC/plasma AUC=
{brain AUC/plasma AUC(KO)}/{brain AUC/plasma AUC(Wild)}

FORMULATION EXAMPLE

(1258) The following Formulation Example s are only exemplified and not intended to limit the scope of the invention.

FORMULATION EXAMPLE

Formulation Example 1: Tablets

(1259) The compounds of the present invention, lactose and calcium stearate are mixed. The mixture is crushed, granulated and dried to give a suitable size of granules. Next, calcium stearate is added to the granules, and the mixture is compressed and molded to give tablets.

Formulation Example 2: Capsules

(1260) The compounds of the present invention, lactose and calcium stearate are mixed uniformly to obtain powder medicines in the form of powders or fine granules. The powder medicines are filled into capsule containers to give capsules.

Formulation Example 3: Granules

(1261) The compounds of the present, invention, lactose and calcium stearate are mixed uniformly and the mixture is compressed and molded. Then, it is crushed, granulated and sieved to give suitable sizes of granules.

Formulation Example 4: Orally Dispersing Tablets

(1262) The compounds of the present invention and crystalline cellulose are mixed, granulated and tablets are made to give orally dispersing tablets.

Formulation Example 5: Dry Syrups

(1263) The compounds of the present invention and lactose are mixed, crushed, granulated and sieved to give suitable sizes of dry syrups.

Formulation Example 6: Injections

(1264) The compounds of the present invention and phosphate buffer are mixed to give injections.

Formulation Example 7: Infusions

(1265) The compounds of the present invention and phosphate buffer are mixed to give infusions.

Formulation Example 8: Inhalations

(1266) The compound of the present invention and lactose are mixed and crushed finely to give inhalations.

Formulation Example 9: Ointments

(1267) The compounds of the present invention and petrolatum are mixed to give ointments.

Formulation Example 10: Patches

(1268) The compounds of the present invention and base such as adhesive plaster or the like are mixed to give patches.

INDUSTRIAL APPLICABILITY

(1269) The compounds of the present invention have an antagonistic activity for the P2X7 receptor and are considered to be useful as a therapeutic and/or preventive agent for diseases or conditions associated with the P2X7 receptor.