HYDROXAMIC ACID DERVICATIVES AS INHIBITORS OF HDAC ENZYMATIC ACTIVITY

摘要

Compounds of formula (I) are inhibitors of histone deacetylase activity, and are useful in the treatment of, for example, cancers: formula (I) wherein Y¹ is a bond, -(C=O)-, -S(O₂)-, -C(=O)O-, -OC(=O)-, -(C=O)NR₃, -NR₃(C=O)-, -S(O₂)NR₃-, -NR₃S(O₂)-, or -NR₃(C=O)NR₅-, wherein R₃ and R₅ are independently hydrogen or optionally substituted (C₁-C₆)alkyl, L¹ is a divalent radical of formula -(Alk¹)_m(Q)_n(Alk²)_p- wherein m, n, p, AIk¹, AIk² and Q are as defined in the claims; z is O 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 R₁ is a carboxylic acid group (-COOH), or an ester group which is hydrolysable by one or more intracellular carboxylesterase enzymes to a carboxylic acid group; R₄ is hydrogen; or optionally substituted C₁-C₆ alkyl, C₃-C₇cycloalkyl, aryl, aryl(C₁-C₆ alkyl)-, heteroaryl, heteroaryl(C₁-C₆ alkyl)-, -(C=O)R₃, -(C=O)OR₃, or -(C=O)NR₃ wherein R₃ is hydrogen or optionally substituted (C₁-C₆)alkyl, C₃-C₇ cycloalkyl, aryl, aryl(C₁-C₆ alkyl)-, heteroaryl, or heteroary(C₁-C₆ alkyl)-; R₄