Sulfonamide compounds having TRPM8 antagonistic activity

Patent metadata

Field	Value
Publication number	US-9540360-B2
Application number	US-201514620360-A
Country	US
Kind code	B2
Filing date	Feb 12, 2015
Priority date	Mar 16, 2011
Publication date	Jan 10, 2017
Grant date	Jan 10, 2017

Abstract

Sulfonamide compounds having TRPM8 antagonistic activity are provided. A sulfonamide compound of formula (I) or a pharmaceutically acceptable salt thereof, or a prodrug thereof:

wherein Ring A is bicyclic aromatic heterocycle comprised of (a) pyridine is condensed with benzene; or (b) pyridine is condensed with monocyclic aromatic heterocycle, and Ring A binds to a sulfonylamino moiety on a carbon atom adjacent to a nitrogen atom of the pyridine ring constituting Ring A,
Ring B is (a) monocyclic or bicyclic aromatic hydrocarbon; (b) monocyclic or bicyclic alicyclic hydrocarbon; (c) monocyclic or bicyclic aromatic heterocycle; or (d) monocyclic or bicyclic non-aromatic heterocycle, Ring C is (a) benzene; or (b) monocyclic aromatic heterocycle, and other symbols are the same as defined in the specification.

First claim

The invention claimed is:

1. A method for treating a disease or condition selected from chronic pain, cephalalgia, urologic disease, carcinoma, respiratory disease, gastrointestinal disease, psychiatric disease, neurological disease, and dermatosis, the method comprising administering to a subject an effective amount of a compound of the following formula:

is bicyclic aromatic heterocycle comprised of pyridine condensed with benzene,
one of Y and Z is CR 2d , and the other is a chemical bond
Ring B is (a) monocyclic or bicyclic aromatic hydrocarbon; (b) monocyclic or bicyclic alicyclic hydrocarbon; (c) monocyclic or bicyclic aromatic heterocycle; or (d) monocyclic or bicyclic non-aromatic heterocycle,
Ring C is (a) benzene; or (b) monocyclic aromatic heterocycle,
R 1 is (a) hydrogen; (b) optionally substituted alkyl; (c) optionally substituted cycloalkyl; (d) optionally substituted alkoxy; (e) optionally substituted phenyl; (f) halogen; or (g) nitrile,
R 2a , R 2b , R 2c and R 2d are each independently (a) hydrogen; (b) optionally substituted alkyl; (c) optionally substituted cycloalkyl; (d) optionally substituted alkoxy; (e) optionally substituted phenyl; (f) optionally substituted monocyclic aromatic heterocyclic group; (g) optionally substituted monocyclic non-aromatic heterocyclic group; (h) halogen; or (i) nitrile,
R 3a , R 3b , R 3c and R 3d are each independently (a) hydrogen; (b) optionally substituted alkyl; (c) optionally substituted cycloalkyl; (d) optionally substituted alkoxy; (e) optionally substituted cycloalkoxy; (f) optionally substituted phenyl; (g) optionally substituted monocyclic aromatic heterocyclic group; (h) optionally substituted monocyclic non-aromatic heterocyclic group; (i) optionally substituted phenoxy; (j) halogen; or (k) hydroxy, or

two substituent groups selected from R 3a , R 3b , R 3c and R 3d combine each other to form oxo,
R 5 and R 6 are each independently (a) hydrogen; (b) alkyl; (c) halogenoalkyl; (d) cycloalkyl; or (e) halogenocycloalkyl, or R 5 and R 6 combine each other at their terminals together with the adjacent carbon atom to form monocyclic alicyclic hydrocarbon,
n is 0, 1 or 2,
X is carboxy, alkoxycarbonyl, hydroxyalkyl, optionally substituted aminocarbonyl, or optionally substituted alkanoyl; or a pharmaceutically acceptable salt thereof.

2. The method of claim 1 , wherein R 1 is (a) hydrogen; (b) C 1 -C 6 alkyl which may be optionally substituted by 1 to 7 groups selected from C 3 -C 7 cycloalkyl, C 1 -C 6 alkoxy, halogen, oxo and hydroxy; (c) C 3 -C 7 cycloalkyl which may be optionally substituted by 1 to 7 groups selected from C 1 -C 6 alkyl, C 1 -C 6 alkoxy and halogen; (d) C 1 -C 6 alkoxy which may be optionally substituted by 1 to 7 groups selected from C 3 -C 7 cycloalkyl, C 1 -C 6 alkoxy, halogen and hydroxy; (e) phenyl which may be optionally substituted by 1 to 3 groups selected from C 1 -C 6 alkyl, C 1 -C 6 halogenoalkyl, C 3 -C 7 cycloalkyl, C 3 -C 7 halogenocycloalkyl, C 1 -C 6 alkoxy, C 1 -C 6 halogenoalkoxy and halogen; (f) halogen; or (g) nitrile,
R 2a , R 2b , R 2c and R 2d are each independently (a) hydrogen; (b) C 1 -C 6 alkyl which may be optionally substituted by 1 to 7 groups selected from C 1 -C 6 alkoxy, C 3 -C 7 cycloalkyl, halogen, oxo and hydroxy; (c) C 3 -C 7 cycloalkyl which may be optionally substituted by 1 to 7 groups selected from C 1 -C 6 alkyl, C 1 -C 6 alkoxy and halogen; (d) C 1 -C 6 alkoxy which may be optionally substituted by 1 to 7 groups selected from C 1 -C 6 alkoxy, C 3 -C 7 cycloalkyl and halogen; (e) phenyl which may be optionally substituted by 1 to 3 groups selected from C 1 -C 6 alkyl, C 1 -C 6 halogenoalkyl, C 3 -C 7 cycloalkyl, C 3 -C 7 halogenocycloalkyl, C 1 -C 6 alkoxy, C 1 -C 6 halogenoalkoxy and halogen; (f) 5 to 6-membered monocyclic aromatic heterocyclic group which may be optionally substituted by 1 to 3 groups selected from C 1 -C 6 alkyl, C 1 -C 6 halogenoalkyl, C 3 -C 7 cycloalkyl, C 3 -C 7 halogenocycloalkyl, C 1 -C 6 alkoxy, C 1 -C 6 halogenoalkoxy and halogen; (g) 4 to 7 membered monocyclic non-aromatic heterocyclic group which may be optionally substituted by 1 to 3 groups selected from C 1 -C 6 alkyl, C 1 -C 6 halogenoalkyl, C 3 -C 7 cycloalkyl, C 3 -C 7 halogenocycloalkyl, C 1 -C 6 alkoxy, C 1 -C 6 halogenoalkoxy and halogen; (h) halogen; or (i) nitrile,
R 3a , R 3b , R 3c and R 3d are each independently (a) hydrogen; (b) C 1 -C 6 alkyl which may be optionally substituted by 1 to 7 groups selected from C 3 -C 7 cycloalkyl, C 3 -C 7 halogenocycloalkyl (in which the cycloalkyl and halogenocycloalkyl may be each independently optionally substituted by 1 to 3 groups selected from C 1 -C 6 alkyl and C 1 -C 6 halogenoalkyl), C 1 -C 6 alkoxy, C 1 -C 6 halogenoalkoxy, phenyl, 5 to 6-membered monocyclic aromatic heterocyclic group, 4 to 7-membered monocyclic non-aromatic heterocyclic group (in which the phenyl, aromatic heterocyclic group and non-aromatic heterocyclic group may be each independently optionally substituted by 1 to 3 groups selected from C 1 -C 6 alkyl, C 1 -C 6 halogenoalkyl, C 3 -C 7 cycloalkyl, C 3 -C 7 halogenocycloalkyl, C 1 -C 6 alkoxy, C 1 -C 6 halogenoalkoxy and halogen), halogen, oxo and hydroxy; (c) C 3 -C 7 cycloalkyl which may be optionally substituted by 1 to 7 groups selected from C 1 -C 6 alkyl, C 1 -C 6 halogenoalkyl, C 1 -C 6 alkoxy, C 1 -C 6 halogenoalkoxy, halogen and hydroxy; (d) C 1 -C 6 alkoxy which may be optionally substituted by 1 to 7 groups selected from C 3 -C 7 cycloalkyl, C 3 -C 7 halogenocycloalkyl (in which the cycloalkyl and halogenocycloalkyl may be each independently optionally substituted by 1 to 3 groups selected from C 1 -C 6 alkyl and C 1 -C 6 halogenoalkyl), C 1 -C 6 alkoxy, C 1 -C 6 halogenoalkoxy, phenyl, 5 to 6-membered monocyclic aromatic heterocyclic group, 4 to 7-membered monocyclic non-aromatic heterocyclic group (in which the phenyl, aromatic heterocyclic group and non-aromatic heterocyclic group may be each independently optionally substituted by 1 to 3 groups selected from C 1 -C 6 alkyl, C 1 -C 6 halogenoalkyl, C 3 -C 7 cycloalkyl, C 3 -C 7 halogenocycloalkyl, C 1 -C 6 alkoxy, C 1 -C 6 halogenoalkoxy and halogen), halogen and hydroxy; (e) C 3 -C 7 cycloalkoxy which may be optionally substituted by 1 to 7 groups selected from C 1 -C 6 alkyl, C 1 -C 6 halogenoalkyl, C 1 -C 6 alkoxy, C 1 -C 6 halogenoalkoxy, halogen and hydroxy; (f) phenyl which may be optionally substituted by 1 to 3 groups selected from C 1 -C 6 alkyl, halogenoalkyl, C 3 -C 7 cycloalkyl, C 3 -C 7 halogenocycloalkyl, C 1 -C 6 alkoxy, C 1 -C 6 halogenoalkoxy and halogen; (g) 5 to 6-membered monocyclic aromatic heterocyclic group which may be optionally substituted by 1 to 3 groups selected from C 1 -C 6 alkyl, C 1 -C 6 halogenoalkyl, C 3 -C 7 cycloalkyl, C 3 -C 7 halogenocycloalkyl, C 1 -C 6 alkoxy, C 1 -C 6 halogenoalkoxy and halogen; (h) 4 to 7-membered monocyclic non-aromatic heterocyclic group which may be optionally substituted by 1 to 3 groups selected from C 1 -C 6 alkyl, C 1 -C 6 halogenoalkyl, C 3 -C 7 cycloalkyl, C 3 -C 7 halogenocycloalkyl, C 1 -C 6 alkoxy, C 1 -C 6 halogenoalkoxy and halogen; (i) phenoxy which may be optionally substituted by 1 to 3 groups selected from C 1 -C 6 alkyl, C 1 -C 6 halogenoalkyl, C 3 -C 7 cycloalkyl, C 3 -C 7 halogenocycloalkyl, C 1 -C 6 alkoxy, C 1 -C 6 halogenoalkoxy and halogen; (j) halogen; or (k) hydroxy, or two substituent groups selected from R 3a , R 3b , R 3c and R 3d combine each other to form oxo,
R 5 and R 6 are each independently (a) hydrogen; (b) C 1 -C 6 alkyl; (c) C 1 -C 6 halogenoalkyl; (d) C 3 -C 7 cycloalkyl; or (e) C 3 -C 7 halogenocycloalkyl, or R

Assignees

• Tsuzuki Yasuyuki
• Sawamoto Daisuke
• Sakamoto Toshiaki
• Kato Taku
• Niwa yasuki
• Awai Nobumasa
• Mitsubishi Tanabe Pharma Corp

Inventors

• Tsuzuki Yasuyuki
• Sawamoto Daisuke
• Sakamoto Toshiaki
• Kato Taku
• Niwa yasuki
• Awai Nobumasa

Classifications

• A61P43/00

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

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P9/12

  Antihypertensives · CPC title

• A61P25/24

  Antidepressants · CPC title