Tetrazolyl-substituted quinuclidines as substance p antagonists

Details Tetrazolyl-substituted quinuclidines as substance p antagonists Tetrazolyl-substituted quinuclidines as substance p antagonists

C - Chemistry, Metallurgy

07

D

C07D 453/02 (2006.01) A61K 31/435 (2006.01)

Patent

CA 2215020

This invention provides a compound of the formula: (see fig. I) and its pharmaceutically acceptable salts, wherein R1 is halo, C1-C6 alkyl, halo C1-C6 alkyl, C1-C6 alkoxy or halo C1-C6 alkoxy; R2 is hydrogen, C1-C6 alkyl, halo C1-C6 alkyl, C1-C6 alkyl-S-, C1-C6 alkyl-SO-, C1-C6 alkyl-SO2-, cyclopropyl, phenyl, -NH2, -NH(CH3), -NHC(=O)CH3, -N(CH3)2, - N(C2H5)2 or -CH2C(=O)CF3; Ar1 and Ar2 are independently phenyl, halophenyl or thienyl; X is NH, O or S, and Y is hydrogen, -COOR3 or -CONR4R5, wherein R3, R4 and R5 are independently hydrogen or C1-C6 alkyl. These compounds are useful as analgesics or anti-inflammatory agents, or in the treatment of allergic disorders, angiogenesis, CNS disorders, emesis, gastrointestinal disorders, sunburn, urinary incontinence, or diseases, disorders or adverse conditions caused by Helicobacter pylori, or the like, in a mammalian subject, especially human, especially as analgesics or anti-inflammatory agents in the periphery.

La présente invention concerne un composé de formule : (voir fig. I) et ses sels pharmaceutiquement acceptables, où R1 est un groupe halo, alkyle en C1-C6, haloalkyle en C1-C6, alcoxy en C1-C6 ou haloalcoxy en C1-C6; R2 est un atome d'hydrogène, un alkyle en C1-C6, un haloalkyle en C1-C6, un alkyle en C1-C6-S-, un alkyle en C1-C6-SO-, un alkyle en C1-C6-SO2-, un cyclopropyle, un phényle, -NH2, -NH(CH3), -NHC(=O)CH3, -N(CH3)2, - N(C2H5)2 ou -CH2C(=O)CF3; Ar1 et Ar2 sont, indépendamment, un groupe phényle, halophényle ou thiényle; X est NH, O ou S, et Y est un atome d'hydrogène, -COOR3 ou -CONR4R5, où R3, R4 et R5 sont, indépendamment, un atome d'hydrogène ou un alkyle en C1-C6. Ces composés sont utiles comme analgésiques ou agents anti-inflammatoires, ou pour le traitement des allergies, l'angiogenèse, les troubles du SNC, le vomissement, les affections gastro-intestinales, les insolations, l'incontinence urinaire ou les maladies, troubles ou états défavorables causés par Helicobacter pylori, ou un organisme semblable, chez un mammifère, surtout chez l'humain, surtout comme analgésiques ou agents anti-inflammatoires dans les régions périphériques de l'organisme humain.

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