N-pyrrolidin-3-yl-amide derivatives as serotonin and...

C - Chemistry – Metallurgy – 07 – D

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C07D 207/14 (2006.01) A61K 31/40 (2006.01) A61P 13/00 (2006.01) A61P 25/24 (2006.01) A61P 29/00 (2006.01)

Patent

CA 2530159

A compound of Formula (I) and pharmaceutically and/or veterinarily acceptable derivatives thereof, wherein R1 is H, C1_6alkyl, -C(X)Y, C3_8cycloalkyl, aryl, het, aryl-Cl_4alkyl or het-Cl_4alkyl, wherein the cycloalkyl, aryl or het groups are optionally substituted by at least one substituent independently selected from C1_8allkyl, C1_8alkoxy, OH, halo, CF3, OCF3, SCF3, hydroxy- Cl_6alkyl, C1_ 4alkoxy-C1_6alkyl and C1_4alkyl-S-C1_4alkyl; R2 is aryl or heteroaryl, each optionally substituted by at least one substituent independently selected from C1_8alkyl, C1_8alkoxy, OH, halo, CF3, OCF3, SCF3, hydroxy-C1_6alkyl, C1_4alkoxy-C1_6alkyl and C1_4alkyl-S-C1_4alkyl; R3 is C1_6alkyl, C3_8cycloalkyl, C3_8cycloalkyl-C1_6alkyl, aryl, het, aryl-Cl_4alkyl or het-C1_4alkyl, wherein the cycloalkyl, aryl or het groups are optionally substituted by at least one substituent independently selected from C1_6alkyl, C1_6alkoxy, OH, halo, CF3, OCF3, SCF3, hydroxy-C1_6alkyl, C1_4alkoxy - C1_6alkyl and C1_4alkyl-S~C1_4alkyl; X is S or O; Y is H, C1_6alkyl, aryl, het, aryl-C1_4alkyl or het-C1_ 4alkyl; and n is 1 or 2, provided that when n is 1, m is 0 or 1 and when n is 2, m is 0, wherein if m is 0, then * represents a chiral center. The compounds of the invention exhibit activity as both serotonin and noradrenaline re-uptake inhibitors and therefore have utility in a variety of therapeutic areas, for example urinary incontinence.

L'invention concerne un composé de formule (I) et ses dérivés acceptables sur un plan pharmaceutique et/ou vétérinaire. Dans cette formule, R?1¿ est H, C¿1?_¿6?alkyle, -C(X)Y, C¿3?_¿8?cycloalkyle, aryle, het, aryl-C¿1?_¿4?alkyle ou het-C¿1?_¿4?alkyle, les groupes cycloalkyle, aryle ou het étant éventuellement substitués par au moins un substituant choisi indépendamment parmi C¿1?_¿8?alkyle, C¿1?_¿8?alkoxy, OH, halo, CF¿3?, OCF¿3?, SCF¿3?, hydroxy-C¿1?_¿6?alkyle, C¿1?_¿4?alkoxy-C¿1?_¿6?alkyle et C¿1?_¿4?alkyl-S-C¿1?_¿4?alkyle; R?2¿ est aryle ou hétéroaryle, chacun éventuellement substitué par au moins un substituant choisi indépendamment parmi C¿1?_¿8?alkyle, C¿1?_¿8?alkoxy, OH, halo, CF¿3?, OCF¿3?, SCF3, hydroxy-C¿1?_¿6?alkyle, C¿1?_¿4?alkoxy-C¿1?_¿6?alkyle et C¿1?_¿4?alkyl-S-C¿1?_¿4?alkyle; R?3¿ est C¿1?_¿6?alkyle, C¿3?_¿8?cycloalkyle, C¿3?_¿8?cycloalkyl-C¿1?_¿6?alkyle, aryle, het, aryl-C¿1?_¿4?alkyle ou het-C¿1?_¿4?alkyle, les groupes cycloalkyle, aryle ou het étant éventuellement substitués par au moins un substituant choisi indépendamment parmi C¿1?_¿6?alkyle, C¿1?_¿6?alkoxy, OH, halo, CF¿3?, OCF¿3?, SCF¿3?, hydroxy-C¿1?_¿6?alkyle, C¿1?_¿4?alkoxy - C¿1?_¿6?alkyle et C¿1?_¿4?alkyl-S-C¿1?_¿4?alkyle; X est S ou O; Y est H, C¿1?_¿6?alkyle, aryle, het, aryl-C¿1?_¿4?alkyle ou het-C¿1?_¿4?alkyle; et n vaut 1 ou 2, à condition que lorsque n est égal à 1, m soit égal à 0 ou 1 et que lorsque n est égal à 2, m soit égal à 0, * représentant un centre chiral si m est égal à 0. Ces composés présentent une activité en tant qu'inhibiteurs du recaptage de la sérotonine et de la noradrénaline et sont donc utiles dans une grande variété de domaines thérapeutiques, par exemple l'incontinence urinaire.

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