Spiro-piperidine derivatives and their use as therapeutic...

C - Chemistry – Metallurgy – 07 – D

Patent

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C07D 491/107 (2006.01) A61K 31/435 (2006.01) A61K 31/438 (2006.01) A61K 31/495 (2006.01) A61K 31/53 (2006.01) A61K 31/535 (2006.01) A61K 31/54 (2006.01) A61K 31/695 (2006.01) C07D 491/10 (2006.01) C07D 519/00 (2006.01) C07F 7/10 (2006.01)

Patent

CA 2258052

The present invention relates to compounds of formula (I), wherein R is C1- 6alkyl, C2-6alkenyl, C2-6alkynyl, C3-7cycloalkyl, C3-7cycloalyklC1-4alkyl, which groups are optionally substituted by hydroxy, C1-4alkoxy or NRaRb, where Ra and Rb each independently represent hydrogen or C1-4alkyl; or R is C1- 4alkyl substituted by Ar, and optionally further substituted by one or both of R4 and R5; R1, R2 and R3 represent a variety of substituents; R9 and R10 are each hydrogen, halogen, C1-6alkyl, CH2ORe, oxo, CO2Ra or CONRaRb where Re represents hydrogen, C1-6alkyl or phenyl; X is -CH2, or -CH2CH2-; Y is -CH=, - CH2-, -CH2CH= or -CH2CH2-, with the proviso that the sum total of carbon atoms in X+Y is 2 or 3; and when Y is -CH= or -CH2CH=, the broken line is a double bond; or a pharmaceutically acceptable salt thereof. The compounds are of particular use in the treatment or prevention of pain, inflammation, migraine, emesis and postherpetic neuralgia.

L'invention concerne des composés représentés par la formule (I): (I) dans laquelle R représente alkyle C¿1?-C¿6?, alcényle C¿2?-C¿6?, alcynyle C¿2?-C¿6?, cycloalkyle C¿3?-C¿7?, cycloalkyle C¿3?-C¿7?-alkyle C¿1?-C¿4?, ces groupes étant éventuellement substitués par hydroxy, alcoxy C¿1?-C¿4? ou NR?a¿R?b¿, R?a¿ et R?b¿ représentant indépendamment chacun hydrogène ou alkyle C¿1?-C¿4?; ou R représente alkyle C¿1?-C¿4? substitué par Ar et, éventuellement, encore substitué par un ou les deux dans R?4¿ et R?5¿; R?1¿, R?2¿ et R?3¿ représentent une variété de substituants; R?9¿ et R?10¿ représentent chacun hydrogène, halogène, alkyle C¿1?-C¿6?, CH¿2?OR?e¿, oxo, CO¿2?R?a¿ ou CONR?a¿R?b¿, R?e¿ représentant hydrogène, alkyle C¿1?-C¿6? ou phényle; X représente -CH¿2? ou -CH¿2?CH¿2?-; Y représente -CH=, -CH¿2?-, -CH¿2?CH= ou -CH¿2?CH¿2?- à condition que la somme totale des atomes de carbone dans X+Y soit égale à 2 ou 3; et, quand Y représente -CH= ou -CH¿2?CH=, la ligne discontinue représente une double liaison; ou un de leurs sels acceptables sur le plan pharmaceutique. Ces composés sont particulièrement utiles dans le traitement ou la prévention de la douleur, de l'inflammation, de la migraine, des vomissements et de la névralgie post-herpétique.

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