Hydroxamates as inhibitors of histone deacetylase

Details Hydroxamates as inhibitors of histone deacetylase Hydroxamates as inhibitors of histone deacetylase

C - Chemistry, Metallurgy

07

D

C07D 239/42 (2006.01) A61K 31/506 (2006.01) A61P 7/12 (2006.01) A61P 9/00 (2006.01) A61P 19/02 (2006.01) A61P 25/28 (2006.01) A61P 29/00 (2006.01)

Patent

CA 2668070

Compounds of formula (I), and salts, N-oxides, hydrates and solvates thereof are histone deacetylase inhibitors and are useful in the treatment of cell proliferative diseases, including cancers: wherein Q, V and W independently represent -N= or -C=; B is a divalent radical selected from (B1), (B2), (B3), (B4), (B5) and (B6), wherein the bond marked * is linked to the ring containing Q, V and W through -[Linker1]- and the bond marked ** is linked to A through -[Linker2]-; A is an optionally substituted mono-, bi- or tri-cyclic carbocyclic or heterocyclic ring system; -[Linker1]- and [Linker2]- independently represent a bond, or a divalent linker radical; and R is (a) a radical of formula R1R2CHNH-Y-L1 -X1-(CH2)Z- or (b) a radical of formula R-L1-Y1-(CH2)Z-.

L'invention concerne des composés représentés par la formule (I), et des sels, N-oxydes, hydrates et solvates de ces composés qui sont des inhibiteurs de l'histone désacétylase et sont utiles dans le traitement de maladies de prolifération cellulaire, telles que les cancers. Dans cette formule, Q, V et W représentent indépendamment -N= ou -C=; B représente un radical divalent choisi parmi (B1), (B2), (B3), (B4), (B5) et (B6), la liaison marquée par * est liée au noyau contenant Q, V et W par -[Lieur1]- et la liaison marquée par ** est liée à A par -[Lieur2]-; A représente un système de noyau carbocyclique ou hétérocyclique mono-, bi- ou tri-cyclique, facultativement substitué; -[Lieur1]- et -[Lieur2]- représentent indépendamment une liaison ou un radical de liaison divalent; et R représente (a) un radical de formule R1R2CHNH-Y-L1 -X1-(CH2)Z- ou (b) un radical de formule R-L1-Y1-(CH2)Z-.

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