| 摘要 |
#CMT# #/CMT# Pyrrolopyridine derivatives (I) are new. #CMT# : #/CMT# 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) and their N-oxides, salts, solvates and hydrates are new. X : H or 1-4 of halo, R', OR', CN, CONR 1R 2, NO 2, NR 1R 2, SR, SOR, SO 2R, SO 2NR 1R 2, NR 3COR 4, NR 3SO 2R 5, Ar or Ar(1-5C)alkyl; Ar : aryl or heteroaryl optionally substituted with halo, R', OR', NO 2 or CN; R : 1-6C alkyl; R' : R, 3-7C cycloalkyl, (3-7C)cycloalkyl(1-3C)alkyl or 1-6C fluoroalkyl; Y' : halo, R', OH, OR', CN, CONR 1R 2, NO 2, NR 1R 2, SR, 1-6C fluoroalkylthio, SH, SOR", SO 2R", SO 2NR 1R 2, NR 3COR 4, NR 3SO 2R 5, Ar or Ar(1-5C)alkyl; R" : R, 3-7C cycloalkyl or (3-7C)cycloalkyl(1-6C)alkyl; R 1-R 4H, R, 3-7C cycloalkyl or (3-7C)cycloalkyl(1-3C)alkyl, Ar or Ar(1-5C)alkyl, or NR 1R 2 = azetidine, pyrrolidine, piperidine, azepine, morpholine, thiomorpholine, piperazine or homopiperazine optionally substituted with halo, R', OR', NO 2 or CN; R 5R, 3-7C cycloalkyl or (3-7C)cycloalkyl(1-3C)alkyl, Ar or Ar(1-5C)alkyl; W' : phenyl fused to a 5- to 7-membered heterocycle that contains 1-3 heteroatoms (N, O, S) and is optionally C-substituted with R', oxo, thio, Ar, or Ar(1-5C)alkyl, and optionally N-substituted with R 6 when N is adjacent to CO or with R 7 in other cases, where S and N atoms are optionally oxidized; R 6H, R', Ar or Ar(1-5C)alkyl; R 7R', aryl(1-6C)alkyl, COR', aroyl, aryl(1-6C)alkylcarbonyl, SO 2R', arylsulfonyl, aryl(1-6C)alkylsulfonyl or aryl. An independent claim is also included for a process for preparing (I). #CMT#[Image]#/CMT# #CMT#ACTIVITY : #/CMT# Analgesic; Antiinflammatory; Antidiabetic; Uropathic; Gynecological; Antipsoriatic; Antipruritic; Virucide; Neuroprotective; Antidepressant. #CMT#MECHANISM OF ACTION : #/CMT# TRPV1 receptor antagonist. N-(2-methyl-5-benzothiazolyl)-5-fluoro-1-(4-pyridylmethyl)-1H-pyrrolo[2,3-b]pyridine-2-carboxamide gave 50% inhibition of the current induced by capsaicin on dorsal root ganglions at a concentration of 10 nM. #CMT#USE : #/CMT# (I) are useful for preparing medicaments for preventing or treating pain, inflammation, metabolic disorders, urological disorders, gynecological disorders, gastrointestinal disorders, respiratory disorders, psoriasis, pruritis, skin, eye or mucosal irritations, herpes, shingles, multiple sclerosis and depression (all claimed). #CMT#ORGANIC CHEMISTRY : #/CMT# Preparation (claimed): The process comprises reacting a carboxylic acid derivative of formula (IV) with an amine W'NH 2 (V) or an amide formed by reacting (V) with trimethyl aluminum. B' : OH, Cl or alkoxy. #CMT#[Image]#/CMT# #CMT#EXAMPLE : #/CMT# A solution of 2M trimethylaluminum (0.85 ml) in toluene at room temperature was added drop by drop to 5-Amino-1,2-dimethyl-1H-benzimidazole (0.189 g) in toluene (10.6 ml). The mixture was reacted at 50[deg]C for 30 minutes on addition of ethyl-1-((4-pyridyl)methyl)-1H-pyyrolo[2,3-b]pyridine-2-carboxylate (0.3 g) at reflux for 5 hours. Work up gave N-(1,2-dimethyl-1H-benzimidazol-5-yl)-1-((4-pyridyl)methyl)-1H-pyrrolo[2,3-b]pyridine-2-carboxamide (0.2 g). |
