Medicament for treating cough

Patent metadata

Field	Value
Publication number	US-12233071-B2
Application number	US-202318135499-A
Country	US
Kind code	B2
Filing date	Apr 17, 2023
Priority date	Mar 14, 2018
Publication date	Feb 25, 2025
Grant date	Feb 25, 2025

Abstract

The present invention pertains to a medicament for preventing or treating cough, including, as an active ingredient, a compound having P2X4 receptor antagonistic action, a tautomer, stereoisomer, or pharmaceutically acceptable salt of the compound, or a hydrate or solvate thereof.

First claim

The invention claimed is:

1. A method for treating cough, the method comprising administering, to a subject in need thereof, a therapeutically effective amount of a compound having P2X4 receptor antagonistic action, or pharmaceutically acceptable salt thereof, wherein the compound having P2X4 receptor antagonistic action is a compound being selected from the group consisting of:
(1) a compound having the following formula FI or pharmaceutically acceptable salt thereof;
(2) a compound having the following formula AI or pharmaceutically acceptable salt thereof;
(3) a compound having the following formula GI or pharmaceutically acceptable salt thereof;
(4) a compound having the following formula HI or pharmaceutically acceptable salt thereof;
(5) a compound having the following formula HII or pharmaceutically acceptable salt thereof;
(6) a compound having the following formula EI or pharmaceutically acceptable salt thereof; and
(7) a compound having the following formula BI or pharmaceutically acceptable salt thereof:

wherein R 1F and R 2F are the same or different and represent a hydrogen atom, a C 1-8 alkyl group, a C 3-8 cycloalkyl group, a C 2-8 alkenyl group, a C 1-8 alkoxy group, a C 1-8 alkyl group substituted with 1 to 3 halogen atoms, a C 1-8 alkoxy group substituted with 1 to 3 halogen atoms, a halogen atom, a hydroxyl group, a nitro group, a cyano group, an amino group, a C 1-8 alkylamino group, a C 2-8 dialkylamino group, a C 2-8 acylamino group, a carboxyl group, a C 2-8 acyl group, an alkoxycarbonyl group (the number of carbon atoms in an alkoxy moiety is from 1 to 8), an optionally substituted phenyl group, an optionally substituted pyridyl group, or an aralkyl group (the number of carbon atoms in an aryl moiety is from 6 to 10 and the number of carbon atoms in an alkylene moiety is from 1 to 8), or
R 1F and R 2F are optionally fused with a benzene ring bonded thereto to form a condensed ring selected from a naphthalene ring, a quinoline ring, an isoquinoline ring, a tetrahydronaphthalene ring, an indane ring, a tetrahydroquinoline ring, or a tetrahydroisoquinoline ring and a ring fused with R 1F and R 2F and comprising carbon atoms bonded to respective R 1F and R 2F is optionally substituted with 1 to 4 substituents, which are the same or different, selected from a C 1-8 alkyl group, a C 3-8 cycloalkyl group, a C 2-8 alkenyl group, a C 1-8 alkoxy group, a C 1-8 alkyl group substituted with 1 to 3 halogen atoms, a C 1-8 alkoxy group substituted with 1 to 3 halogen atoms, a halogen atom, a hydroxyl group, a nitro group, a cyano group, an amino group, a C 1-8 alkylamino group, a C 2-8 dialkylamino group, a C 2-8 acylamino group, a carboxyl group, a C 2-8 acyl group, an alkoxycarbonyl group (the number of carbon atoms in an alkoxy moiety is from 1 to 8), or an aralkyl group (the number of carbon atoms in an aryl moiety is from 6 to 10 and the number of carbon atoms in an alkylene moiety is from 1 to 8),
R 3F and R 4F are the same or different and represent a hydrogen atom, a C 1-8 alkyl group, a C 2-8 alkenyl group, a C 1-8 alkoxy group, a C 1-8 alkyl group substituted with 1 to 3 halogen atoms, a C 1-8 alkoxy group substituted with 1 to 3 halogen atoms, a halogen atom, a hydroxyl group, a nitro group, a cyano group, an amino group, a C 1-8 alkylamino group, a C 2-8 dialkylamino group, a C 2-8 acylamino group, a carboxyl group, a C 2-8 acyl group, an alkoxycarbonyl group (the number of carbon atoms in an alkoxy moiety is from 1 to 8), or an aralkyl group (the number of carbon atoms in an aryl moiety is from 6 to 10 and the number of carbon atoms in an alkylene moiety is from 1 to 8),
R 5F represents a hydrogen atom, a C 1-8 alkyl group, a C 2-8 alkenyl group, a C 1-8 alkyl group substituted with 1 to 3 halogen atoms, a hydroxyl-substituted C 1-8 alkyl group, or an aralkyl group (the number of carbon atoms in an aryl moiety is from 6 to 10 and the number of carbon atoms in an alkylene moiety is from 1 to 8),
R 6F and R 7F represent a hydrogen atom,
X F represents C,
Y F represents N, a double line composed of a solid line and a dashed line denotes a double bond,
Z F represents an oxygen atom,
A F represents a bond or represents a benzene ring, a pyridine ring, a thiophene ring, a pyrimidine ring, a naphthalene ring, a quinoline ring, or an indole ring optionally having, as substituents, 1 to 4 substituents, which are the same or different, selected from a C 1-8 alkyl group, a C 2-8 alkenyl group, a C 1-8 alkoxy group, a C 1-8 alkyl group substituted with 1 to 3 halogen atoms, a C 1-8 alkoxy group substituted with 1 to 3 halogen atoms, a halogen atom, a hydroxyl group, a nitro group, a cyano group, an amino group, a C 1-8 alkylamino group, a C 2-8 dialkylamino group, an aralkyl group (the number of carbon atoms in an aryl moiety is from 6 to 10 and the number of carbon atoms in an alkylene moiety is from 1 to 8), a phenyl group, or a pyridyl group,
B F represents N(R 8F )C(═O), NHCONH, CON(R 9F ), NHC(═S)NH, N(R 10F ) SO 2 , SO 2 N(R 11F ), or OSO 2 ,
R 8F , R 9F , R 10F , and R 11F here represent a hydrogen atom, a C 1-8 alkyl group, a C 1-8 alkyl group substituted with 1 to 3 halogen atoms, a hydroxyl-substituted C 1-8 alkyl group, or an aralkyl group (the number of carbon atoms in an aryl moiety is from 6 to 10 and the number of carbon atoms in an alkylene moiety is from 1 to 8),
D F represents a bond or a C 1-6 alkylene chain optionally having, as substituents, 1 to 4 substituents, which are the same or different, selected from a C 1-8 alkyl group, a C 2-8 alkenyl group, a C 1-8 alkyl group substituted with 1 to 3 halogen atoms, a hydroxyl-substituted C 1-8 alkyl group, or an aralkyl group (the number of carbon atoms in an aryl moiety is from 6 to 10 and the number of carbon atoms in an alkylene moiety is from 1 to 8) and further optionally having a double bond,
E F represents O, S, NR 12F , or a bond,
R 12F here represents a hydrogen atom, a C 1-8 alkyl group, a C 2-8 alkenyl group, a C 1-8 alkyl group substituted with 1 to 3 halogen atoms, a hydroxyl-substituted C 1-8 alkyl group, or an aralkyl group (the number of carbon atoms in an aryl moiety is from 6 to 10 and the number of carbon atoms in an alkylene moiety is from 1 to 8),
G F represents piperazine, piperidine, morpholine, cyclohexane, benzene, naphthalene, quinoline, quinoxaline, benzimidazole, thiophene, imidazole, thiazole, oxazole, indole, benzofuran, pyrrole, pyridine or pyrimidine optionally having, as substituents, 1 to 4 substituents, which are the same or different, selected from a C 1-8 alkyl group, a C 2-8 alkenyl group, a C 1-8 alkoxy group, a C 1-8 alkyl group substituted with 1 to 3 halogen atoms, a C 1-8 alkoxy group substituted with 1 to 3 halogen atoms, a halogen atom, a hydroxyl group, a nitro group, a cyano group, an amino group, a C 1-8 alkylamino group, a C 2-8 dialkylamino group, a C 2-8 acyl group, a methylenedioxy group, a carboxyl group, a C 1-6 alkylsulfinyl group, a C 1-6 alkylthio group, a C 1-6 alkylsulfonyl group, an aralkyl group (the number of carbon atoms in an aryl moiety is from 6 to 10 and the number of carbon atoms in an alkylene moiety is from 1 to 8), an optionally substituted phenyl, an optionally substituted pyridyl group, an optionally substituted imidazolyl group, an optionally substituted oxazolyl group, or an optionally substituted thiazolyl group, and
m F represents an integer of 0 to 5,
provided that a case is excluded where R 1F and R 2F are not fused to form a ring and where X F is C, YF is N, the double line composed of a solid line and a dashed line d

Assignees

• Nippon Chemiphar Co

Inventors

• Imai Toshiyasu
• Kamei Junzo

Classifications

• A61P11/14

  Antitussive agents · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61K31/517

  ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine · CPC title

• A61K31/498

  Pyrazines or piperazines ortho- and peri-condensed with carbocyclic ring systems, e.g. quinoxaline, phenazine · CPC title

• A61K31/5513 Primary

  1,4-Benzodiazepines, e.g. diazepam {or clozapine} · CPC title