ENZYME INHIBITORS

摘要

Compounds of formula (I), inhibit HDAC activity: wherein A, B and D independently represent =CH- or =N-; W is-CH=CH- Or -CH2CH2-; 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; R2 and R3 are selected from the side chains of a natural or non-natural alpha amino acid, provided that neither R2 nor R3 is hydrogen, or R2 and R3, taken together with the carbon to which they are attached, form a 3-6 membered saturated cycloalkyl or heterocyclyl ring; Y is a bond, -C(=O)-, -S(=O)2-, -C(=O)O-, -C(=O)NR'-, -C(=S)-NR', -C(=NH)NR' or -S(=O)2NR - wherein R' is hydrogen or optionally substituted C1-C6 alkyl; L1 is a divalent radical of formula -(Alk1)m(Q)n(Alk2)p- wherein m, n, p, Q, AIk1 and AIk2 are as defined in the claims; X1 represents a bond; -C(=O); or -S(=O)2-; -NR4C(=O)-, -C(=O)NR4-,- NR4C(=O)NR5-, -NR4S(=O)2-, or -S(=O)2NR4- wherein R4 and R5 are independently hydrogen or optionally substituted C1-C6 alkyl; and z is 0 or 1.