DERIVATIVES OF N-(HETEROARYL)-1-HETEROARYL-1H-INDOL-2-CARBOXAMIDS, PREPARATION THEREOF AND THERAPEUTIC USE THEREOF

摘要

N-(Benzo-heterocyclyl)-1-heteroaryl-1H-indole-2-carboxamide derivatives (I) are new. Indole derivatives of formula (I) and their acid addition salts, hydrates and solvates are new. X 1-X 4H, halo, alkyl, cycloalkyl, cycloalkyl-(1-3C) alkyl, fluoroalkyl, alkoxy, fluoroalkoxy, CN, CONR 1R 2, NO 2, NR 1R 2, alkylthio, alkylsulfinyl, alkylsulfonyl, SO 2NR 1R 2, NR 3COR 4, NR 3SO 2R 5 or aryl (optionally substituted (os) by one or more of alkyl, cycloalkyl, cycloalkyl-(1-3C) alkyl, fluoroalkyl, alkoxy, fluoroalkoxy, CN or NO 2); W' : benzo-fused 5-7 membered heterocycle, (i) containing 1-3 of S, O and/or N as heteroatom(s), (ii) bonded to the N of (I) via the benzo ring, (iii) os on C of the heterocyclic ring by one or more of alkyl, cycloalkyl, cycloalkyl-(1-3C) alkyl, fluoroalkyl, alkoxy, cycloalkoxy, cycloalkyl-(1-3C) alkoxy, aryl, arylalkyl, = O or thio and (iv) os on N by R 6 if the N is adjacent to = O or in other cases by R 7; Y' : heteroaryl (os by one or more of halo, alkyl, cycloalkyl, cycloalkyl-(1-3C) alkyl, fluoroalkyl, OH, alkoxy, fluoroalkoxy, CN, CONR 1R 2, NO 2, NR 1R 2, alkylthio, SH, alkylsulfinyl, alkylsulfonyl, cycloalkylsulfinyl, cycloalkylsulfonyl, SO 2NR 1R 2, NR 3COR 4, NR 3SO 2R 5, aryl or arylalkyl (where aryl moieties are os as in X 1-X 4); R 1, R 2H, alkyl, cycloalkyl, cycloalkyl-(1-3C) alkyl, arylalkyl or aryl; or NR 1R 2azetidino, pyrrolidone, piperidino, azepino, morpholino, thiomorpholino, piperazino or homopiperazino (all os by alkyl, cycloalkyl, cycloalkyl-(1-3C) alkyl, arylalkyl or aryl); R 3, R 4H, alkyl, arylalkyl or aryl; R 5alkyl, arylalkyl or aryl; R 6H, alkyl, cycloalkyl, cycloalkyl-(1-3C) alkyl, fluoroalkyl, arylalkyl, alkylcarbonyl, cycloalkyl-(1-3C) alkylcarbonyl, fluoroalkylcarbonyl, cycloalkylcarbonyl, arylcarbonyl, arylalkylcarbonyl, alkylsulfonyl, fluoroalkylsulfonyl, cycloalkylsulfonyl, cycloalkyl-(1-3C) alkylsulfonyl, arylsulfonyl or aryl; ring S and N atoms in W' and Y' are optionally in oxidized form; unless specified otherwise alkyl moieties have 1-6C and cycloalkyl moieties 3-7C. An independent claim is included for the preparation of (I) [Image] ACTIVITY : Analgesic; Antiinflammatory; Urolopathic; Gynecological; Antipsoriatic; Antipruritic; Dermatological; Ophthalmological; Virucide; Neuroprotective; Antidepressant; Antiulcer; Hepatotropic; Antiasthmatic; Antitussive. MECHANISM OF ACTION : TRPV1 receptor antagonist. In a TRPV1 receptor antagonist assay based on inhibtion of the current induced in rat dorsal root ganglions, N-(1,2-dimethyl-1H-benzimidazol-5-yl)-5-fluoro-1-(4,6-dimethyl-pyridin-2-yl)-1H-indole-2-carboxamide (Ia) gave 70% inhibition at a concentration of 10 nM.