Substituted benzolactam compounds as substance p antagonists

Details Substituted benzolactam compounds as substance p antagonists Substituted benzolactam compounds as substance p antagonists

C - Chemistry, Metallurgy

07

D

C07D 401/12 (2006.01) A61K 31/40 (2006.01) A61K 31/435 (2006.01) A61K 31/535 (2006.01) A61K 31/54 (2006.01) A61K 31/55 (2006.01) C07D 413/12 (2006.01) C07D 417/12 (2006.01) C07D 453/02 (2006.01) C07D 471/08 (2006.01)

Patent

CA 2226292

This invention provides a compound of general formula (I) and its pharmaceutically acceptable salts, wherein: W is methylene, ethylene, propylene, vinylene, -CH2-O-, -O-CH2-, -CH2-S- or -S-CH2-; R1, R2 and R3 are independently hydrogen, C1-C3 alkyl, C1-C3 alkoxy or halo C1-C3 alkyl, provided that when W is methylene, both R2 and R3 are not hydrogen; X is halo, C1-C3 alkoxy, C1-C3 alkyl, halo C1-C3 alkoxy or C1-C3 alkenyl; Y is imino or oxy; Q is oxygen or sulfur; and T is (2S,3S)-2-diphenylmethylquinuclidin-3-yl, (2S,3S)-2-phenylpiperidin-3-yl or (2S,3S)-2-diphenylmethyl-1-azanorbornan-3- yl. These compounds are useful in the treatment of treating gastrointestinal disorders, central nervous system disorders, inflammatory diseases, emesis, urinary incontinence, pain, migraine, angiogensis or the like in a mammaliam subject, especially humans. Also, intermediates of the above compounds are disclosed.

L'invention concerne un composé présentant la formule générale (I), et ses sels pharmaceutiquement acceptables. Dans la formule, W représente méthylène, éthylène, propylène, vinylène, -CH¿2?-O-, -O-CH¿2?, -CH¿2?-S- ou -S-CH¿2?-; R?1¿, R?2¿ et R?3¿ représentent indépendamment hydrogène, alkyle C¿1?-C¿3?, alkoxy C¿1?-C¿3? ou halo alkyle C¿1?-C¿3? à condition que lorsque W représente méthylène, R?2¿ et R?3¿ ne représentent pas hydrogène; X représente halo, alkoxy C¿1?-C¿3?, alkyle C¿1?-C¿3?, halo alkoxy C¿1?-C¿3? ou alcényle C¿1?-C¿3?; Y représente imino ou oxy; Q représente oxygène ou soufre, et T représente (2S,3S)-2-diphénylméthylquinuclidine-3-yle, (2S-3S)-2-phénylpipéridin-3-yle ou (2S-3S)-2-diphénylméthyl-1-azanobornan-3-yle. Ces composés sont utilisés dans le traitement de troubles gastro-intestinaux, de troubles du système nerveux central, de maladies inflammatoires, des vomissements, de l'incontinence urinaire, des douleurs, de la migraine, de l'angiogénèse ou similaires chez le mammifère, et en particulier, chez l'homme. L'invention concerne également des intermédiaires des composés susmentionnés.

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