Patent FR-2910473-A1 (FR)
Title: New pyrrolopyridine derivatives e.g. useful for treating pain, inflammation, urological disorders, gynecological disorders, gastrointestinal disorders, respiratory disorders, psoriasis, pruritis
Inventor: DUBOIS LAURENT
IPC: A61K31/437
Filed: 2006-12-26
Abstract: Pyrrolo[3,2-b]pyridine, pyrrolo[3,2-c]pyridine, pyrrolo[2,3-c]pyridine or pyrrolo[2,3-b]pyridine derivatives (I) are new. Pyrrolo[3,2-b]pyridine, pyrrolo[3,2-c]pyridine, pyrrolo[2,3-c]pyridine or pyrrolo[2,3-b]pyridine derivatives of formula (I) are new. X : one or more of H, R, 3-7C cycloalkyl, (3-7C)cycloalkyl(1-6C)alkyl, 1-6C fluoroalkyl, OR, 3-7C cycloalkoxy, (3-7C)cycloalkyl(1-6C)alkoxy, 1-6C fluoroalkoxy, CN, SR, SOR, SO 2R, SF 5, CONR 1R 2, SO 2NR 1R 2, NO 2, NR 1R 2, OCONR 1R 2, NR 3COR 4, NR 3CONR 1R 2, NR 3SO 2R 5, NR 3SO 2NR 1R 2, Ar(1-6C)alkyl, Het(1-6C)alkyl, Ar or Het; Ar : aryl optionally substituted with Q; Het : heteroaryl optionally substituted with Q; Q : halo, R, 3-7C cycloalkyl, (3-7C)cycloalkyl(1-6C)alkyl, 1-6C fluoroalkyl, OR, 1-6C fluoroalkoxy, NO 2 or CN; R : 1-6C alkyl; n : 0-3; Y' : aryl or heteroaryl optionally substituted with X; Z 1-Z 4N or CR 6, at least one being N and at least one being CR 6; Z : NRaRb; Ra, Rb : H, R, 3-7C cycloalkyl, (3-7C)cycloalkyl(1-6C)alkyl, 1-6C fluoroalkyl, OH, OR, 3-7C cycloalkoxy, (3-7C)cycloalkyl(1-6C)alkoxy, 1-6C fluoroalkoxy, aryl or heteroaryl, all optionally substituted with Rc, or Ra+Rb= -A-L-B'- forming a ring optionally substituted with R12; A : 1-7C alkylene optionally substituted with 1-2 of R8; B' : 1-7C alkylene optionally substituted with 1-2 of R9; L : a bond, O, S or N, where N is optionally substituted with R10 or R11; Rc : X but not H; R 1, R 2H, R, 3-7C cycloalkyl, (3-7C)cycloalkyl(1-6C)alkyl, Ar(1-6C)alkyl, Ar or Het, or R1+R2= azetidinyl, pyrrolidinyl, piperidinyl, azepinyl, morpholinyl, thiomorpholinyl, piperazinyl or homopiperazinyl, optionally substituted with R, 3-7C cycloalkyl, (3-7C)cycloalkyl(1-6C)alkyl, Ar(1-6C)alkyl, Ar or Het; R 3, R 4= H, R, 3-7C cycloalkyl, (3-7C)cycloalkyl(1-6C)alkyl, Ar(1-6C)alkyl, Ar or Het, or R 3+R 4 or R 3+R 1= 2-5C alkylene; R 5R, 3-7C cycloalkyl, (3-7C)cycloalkyl(1-6C)alkyl, Ar(1-6C)alkyl, Ar or Het, or R 5+R 3= 2-5C alkylene; R 6H, halo, R, 3-7C cycloalkyl, (3-7C)cycloalkyl(1-6C)alkyl, 1-6C fluoroalkyl, OR, 3-7C cycloalkoxy, (3-7C)cycloalkyl(1-6C)alkoxy, 1-6C fluoroalkoxy, CN, SR, SOR, SO 2R, OH, SH, oxo, thio, Ar, Ar(1-6C)alkyl or Het; R 7H, R, 3-7C cycloalkyl, (3-7C)cycloalkyl(1-6C)alkyl, 1-6C fluoroalkyl, OR, 3-7C cycloalkoxy, (3-7C)cycloalkyl(1-6C)alkoxy, 1-6C fluoroalkoxy, Ar, Ar(1-6C)alkyl or Het; R 8+R 8, R 9+R 9, R 8+R 9, R 8+R 10, R 9+R 10a bond or 1-6C alkylene; R 11H, R, 3-7C cycloalkyl, (3-7C)cycloalkyl(1-6C)alkyl, 1-6C fluoroalkyl, OR, 3-7C cycloalkoxy, (3-7C)cycloalkyl(1-6C)alkoxy, 1-6C fluoroalkoxy, OH, COR, COOR 5, CONR 1R 2, Ar(1-6C)alkyl, Ar or Het; R 12F, 1-6C alkyl optionally substituted with R 13, 3-7C cycloalkyl, (3-7C)cycloalkyl(1-6C)alkyl, 1-6C fluoroalkyl, cycloalkylidene, heterocycloalkylidene optionally N-substituted with R 11, OR, 3-7C cycloalkoxy, (3-7C)cycloalkyl(1-6C)alkoxy, 1-6C fluoroalkoxy, COOH, COOR, CONR 1R 2, NR 1R 2, NR 3COR 4, OCONR 1R 2, NR 3COOR 5, NR 3CONR 1R 2, OH, SH, oxo, thio, Ar(1-6C)alkyl or Ar; R 13OR, 3-7C cycloalkoxy, (3-7C)cycloalkyl(1-6C)alkoxy, CONR 1R 2, NR 1R 2, NR 3COR 4, OCONR 1R 2, NR 3COOR 5 or OH, Independent claims are also included for: (1) four processes for preparing (I); (2) 5-amino-2-dimethylamino-3-methylpyridine and 2-amino-5-pyrrolidinopyrazine. [Image] ACTIVITY : Analgesic; Antiinflammatory; Uropathic; Gynecological; Antipsoriatic; Antipruritic; Virucide; Antidepressant. MECHANISM OF ACTION : TRPV1 receptor antagonist. At a concentration of 1 nM, N-(6-dimethylamino-5-trifluoromethyl-3-pyridyl)-5-trifluoromethyl-1-(3-fluorobenzyl)-1H-pyrrolo[2,3-b]pyridine-2-carboxamide gave 98% inhibition of capsaicin-induced current generation in dorsal root ganglion cells.