Hydroxamic acid derivatives as inhibitors of hdac enzymatic activity

Abstract

Compounds of formula (I) are inhibitors of histone deacetylase activity, and are useful in the treatment of, for example, cancers: wherein Yis a bond, —(C═O)—, —S(O)—, —C(═O)O—, —OC(═O)—, —(C═O)NR—, —NR(C═O)—, —S(O)NR—, —NRS(O)—, or —NR(C═O)NR—, wherein Rand Rare independently hydrogen or optionally substituted (C-C)alkyl, Lis a divalent radical of formula -(Alk)(Q)(Alk)wherein m, n, p, Alk, Alkand Q are as defined in the claims; z is 0 or 1; A represents an optionally substituted mono-, bi— or tri-cyclic carbocyclic or heterocyclic ring system; -[Linker]- represents a divalent linker radical; R is a radical of formula (X) or (Y): wherein Ris a carboxylic acid group (—COOH), or an ester group which is hydrolysable by one or more intracellular carboxylesterase enzymes to a carboxylic acid group; Ris hydrogen; or optionally substituted C-Calkyl, C-Ccycloalkyl, aryl, aryl(C-Calkyl)-, heteroaryl, heteroaryl(C-Calkyl)-, —(C═O)R, —(C═O)OR, or —(C═O)NRwherein Ris hydrogen or optionally substituted (C-C)alkyl, C-Ccycloalkyl, aryl, aryl(C-Calkyl)-, heteroaryl, or heteroaryl(C-Calkyl)-; Ris hydrogen or optionally substituted C-Calkyl; and B is a monocyclic heterocyclic ring of 5 or 6 ring atoms wherein Ris linked to a ring carbon adjacent the ring nitrogen shown, and ring B is optionally fused to a second carbocyclic or heterocyclic ring of 5 or 6 ring atoms in which case the bond shown intersected by a wavy line may be from a ring atom in said second ring.