Patent ID: 11918589
Assignee: KYUSHU UNIVERSITY, NATIONAL UNIVERSITY CORPORATION
Field: Pharmaceuticals (Chemistry)
Classification: CPC A | IPC A

Claim 1:
2. A method of therapeutic treatment of multiple sclerosis, the method comprising administering a medicament which contains a compound having P2X4 receptor antagonist activity, or a salt thereof, or a hydrate or solvate thereof as an active ingredient, wherein the cpmpound is a compound represented by the following the general formula (IE):, , wherein, in the formula, R1E and R2E may be the same or different, and represent hydrogen atom, an alkyl group having 1 to 8 carbon atoms, a cycloalkyl group having 3 to 8 carbon atoms, an alkenyl group having 2 to 8 carbon atoms, an alkoxy group having 1 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms and substituted with 1 to 3 halogen atoms, an alkoxy group having 1 to 8 carbon atoms and substituted with 1 to 3 halogen atoms, a halogen atom, hydroxyl group, nitro group, cyano group, amino group, an alkylamino group having 1 to 8 carbon atoms, a dialkylamino group having 2 to 8 carbon atoms, an acylamino group having 2 to 8 carbon atoms, carboxyl group, an acyl group having 2 to 8 carbon atoms, an alkoxycarbonyl group wherein the alkoxy group contains has 1 to 8 carbon atoms, a phenyl group which can have a substituent, a pyridyl group which can have a substituent, or an aralkyl group wherein the aryl group contains 6 to 10 carbon atoms and the alkylene group contains 1 to 8 carbon atoms, or
R1E and R2E can bind together to form a condensed ring selected from naphthalene ring, quinoline ring, isoquinoline ring, tetrahydronaphthalene ring, indane ring, tetrahydroquinoline ring, and tetrahydroisoquinoline ring together with the benzene ring to which they bind, and the ring formed by R1E, R2E binding together, and the carbon atoms to which R1E and R2E bind may be substituted with 1 to 4 of the same or different substituents selected from an alkyl group having 1 to 8 carbon atoms, a cycloalkyl group having 3 to 8 carbon atoms, an alkenyl group having 2 to 8 carbon atoms, an alkoxy group having 1 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms and substituted with 1 to 3 halogen atoms, an alkoxy group having 1 to 8 carbon atoms and substituted with 1 to 3 halogen atoms, a halogen atom, hydroxyl group, nitro group, cyano group, amino group, an alkylamino group having 1 to 8 carbon atoms, a dialkylamino group having 2 to 8 carbon atoms, an acylamino group having 2 to 8 carbon atoms, carboxyl group, an acyl group having 2 to 8 carbon atoms, an alkoxycarbonyl group wherein the alkoxy group contains 1 to 8 carbon atoms, and an aralkyl group wherein the aryl group contains 6 to 10 carbon atoms and the alkylene group contains 1 to 8 carbon atoms,
R3E and R4E may be the same or different, and represent hydrogen atom, an alkyl group having 1 to 8 carbon atoms, an alkenyl group having 2 to 8 carbon atoms, an alkoxy group having 1 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms and substituted with 1 to 3 halogen atoms, an alkoxy group having 1 to 8 carbon atoms and substituted with 1 to 3 halogen atoms, a halogen atom, hydroxyl group, nitro group, cyano group, amino group, an alkylamino group having 1 to 8 carbon atoms, a dialkylamino group having 2 to 8 carbon atoms, an acylamino group having 2 to 8 carbon atoms, carboxyl group, an acyl group having 2 to 8 carbon atoms, an alkoxycarbonyl group wherein the alkoxy group contains 1 to 8 carbon atoms, or an aralkyl group wherein the aryl group contains 6 to 10 carbon atoms and the alkylene group contains 1 to 8 carbon atoms,
R5E represents hydrogen atom, an alkyl group having 1 to 8 carbon atoms, an alkenyl group having 2 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms and substituted with 1 to 3 halogen atoms, an alkyl group having 1 to 8 carbon atoms and substituted with hydroxyl group, or an aralkyl group wherein the aryl group contains 6 to 10 carbon atoms and the alkylene group contains 1 to 8 carbon atoms,
R6E and R7E may be the same or different, and represent hydrogen atom, an alkyl group having 1 to 8 carbon atoms, an alkenyl group having 2 to 8 carbon atoms, an alkoxy group having 1 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms and substituted with 1 to 3 halogen atoms, an alkoxy group having 1 to 8 carbon atoms and substituted with 1 to 3 halogen atoms, a halogen atom, hydroxyl group, or amino group,
XE represents C, CH, or N,
YE represents N, NH, or C(═O),
provided that when XE is N, YE is not N or NH, and
when XE is C or CH, YE is not C(═O),
the double line consisting of the solid line and the broken line represents a single bond or a double bond,
ZE represents oxygen atom or sulfur atom,
AE represents benzene ring, pyridine ring, thiophene ring, pyrimidine ring, naphthalene ring, quinoline ring, or indole ring which can have 1 to 4 of the same or different substituents selected from an alkyl group having 1 to 8 carbon atoms, an alkenyl group having 2 to 8 carbon atoms, an alkoxy group having 1 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms and substituted with 1 to 3 halogen atoms, an alkoxy group having 1 to 8 carbon atoms and substituted with 1 to 3 halogen atoms, a halogen atom, hydroxyl group, nitro group, cyano group, amino group, an alkylamino group having 1 to 8 carbon atoms, a dialkylamino group having 2 to 8 carbon atoms, an aralkyl group wherein the aryl group contains 6 to 10 carbon atoms and the alkylene group contains 1 to 8 carbon atoms, phenyl group, and pyridyl group, or an atomic bond,
BE represents N(R8E)C(═O), NHCONH, CON(R9E), NHC(═S)NH, N(R10E)SO2, SO2N(R11E), or OSO2, wherein
R8E, R9E, R10E, and R11E represent hydrogen atom, an alkyl group having 1 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms and substituted with 1 to 3 halogen atoms, an alkyl group having 1 to 8 carbon atoms and substituted with hydroxyl group, or an aralkyl group wherein the aryl group contains 6 to 10 carbon atoms and the alkylene group contains 1 to 8 carbon atoms,
DE represents an alkylene chain having 1 to 6 carbon atoms which can have 1 to 4 of the same or different substituents selected from an alkyl group having 1 to 8 carbon atoms, an alkenyl group having 2 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms and substituted with 1 to 3 halogen atoms, an alkyl group having 1 to 8 carbon atoms and substituted with hydroxyl group, or an aralkyl group wherein the aryl group contains 6 to 10 carbon atoms and the alkylene group contains 1 to 8 carbon atoms, and may further contain a double bond, or an atomic bond,
EE represents O, S, NR12E, or an atomic bond, wherein
R12E represents hydrogen atom, an alkyl group having 1 to 8 carbon atoms, an alkenyl group having 2 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms and substituted with 1 to 3 halogen atoms, an alkyl group having 1 to 8 carbon atoms and substituted with hydroxyl group, or an aralkyl group wherein the aryl group contains has 6 to 10 carbon atoms and the alkylene group contains 1 to 8 carbon atoms,
GE represents piperazine, piperidine, morpholine, cyclohexane, benzene, naphthalene, quinoline, quinoxaline, benzimidazole, thiophene, imidazole, thiazole, oxazole, indole, benzofuran, pyrrole, pyridine, or pyrimidine which can have 1 to 4 of the same or different substituents selected from an alkyl group having 1 to 8 carbon atoms, an alkenyl group having 2 to 8 carbon atoms, an alkoxy group having 1 to 8 carbon atoms, an alkyl group having 1 to 8 carbon atoms and substituted with 1 to 3 halogen atoms, an alkoxy group having 1 to 8 carbon atoms and substituted with 1 to 3 halogen atoms, a halogen atom, hydroxyl group, nitro group, cyano group, amino group, an alkylamino group having 1 to 8 carbon atoms, a dialkylamino group having 2 to 8 carbon atoms, an acyl group having 2 to 8 carbon atoms, methylenedioxy group, carboxyl group, an alkylsulfinyl group having 1 to 6 carbon atoms, an alkylthio group having 1 to 6 carbon atoms, an alkylsulfonyl group having 1 to 6 carbon atoms, an aralkyl group wherein the aryl group contains 6 to 10 carbon atoms and the alkylene group contains 1 to 8 carbon atoms, a phenyl group which can have a substituent, a pyridyl group which can have a substituent, an imidazolyl group which can have a substituent, an oxazolyl group can have a substituent, and a thiazolyl group which can have a substituent, and
mE represents an integer of 0 to 5,
provided that compounds where R1E and R2E do not bind together to form a ring, XE is C, YE is N, the double line consisting of the solid line and the broken line is a double bond, ZE is oxygen atom, AE is a benzene ring, mE is 0, BE is C(═O)NH, EE is an atomic bond, and GE is phenyl group are excluded.