Spirocyclic derivatives as histone deacetylase inhibitors

Details Spirocyclic derivatives as histone deacetylase inhibitors Spirocyclic derivatives as histone deacetylase inhibitors

C - Chemistry, Metallurgy

07

D

C07D 471/10 (2006.01) A61K 31/438 (2006.01) A61K 31/527 (2006.01) A61P 35/00 (2006.01) C07D 491/107 (2006.01)

Patent

CA 2721467

This invention is related to new histone deacetylase inhibitors according to the general formula (I) wherein: the dotted line is an optional additional bond; n is zero or an integer from 1 to 4; R1 is hydrogen; C1-C6 alkyl, optionally substituted by cycloalkyl, aryl or by heteroaryl; (CO)R3; (SO2)R4; cycloalkyl; aryl; or heteroaryl; R2 is C1-C6 alkyl, optionally substituted by aryl or by heteroaryl; aryl; heteroaryl; or (CO)R5; X is CH2, oxygen or NR6; Y is a bond, CHR7 or NR8; Z is oxygen, CR9R10 or C=R11; and R3, R4, R5, R6, R7, R8, R9, R10 and R11 are as further defined in the specification; and pharmaceutical acceptable salts thereof.

Cette invention concerne de nouveaux inhibiteurs de lhistone désacétylase répondant à la formule générale (I) dans laquelle : la ligne pointillée est une liaison supplémentaire facultative ; n vaut zéro ou est un entier de 1 à 4 ; R1 est un hydrogène, un alkyle en C1-C6, facultativement substitué par un cycloalkyle, un aryle ou par un hétéroaryle ; (CO)R3 ; (SO2)R4 ; un cycloalkyle ; un aryle ; ou un hétéroaryle ; R2 est un alkyle en C1-C6, facultativement substitué par un aryle ou par un hétéroaryle ; un aryle ; un hétéroaryle ; ou (CO)R5 ; X est CH2, un oxygène ou NR6 ; Y est une liaison, CHR7 ou NR8 ; Z est un oxygène, CR9R10 ou C=R11 ; et R3, R4, R5, R6, R7, R8, R9, R10 et R11 sont tels que définis plus loin dans la description. L'invention concerne également des sels pharmaceutiques acceptables de ceux-ci.

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