Compounds of formula (I) are inhibitors of
histone deacetylase activity, and are useful in the treatment of, for example, cancers, wherein R1 is a
carboxylic acid group (—COOH), or an ester group which is hydrolysable by one or more
intracellular carboxyesterase enzymes to a
carboxylic acid group; R2 is the
side chain of a natural or non-natural
alpha amino acid; Y is a bond, C(═O)—, —S(═O)2—, —C(—O)O—, —C(O)NR3—, —C(═S)—NR3, —C(═NH)NR3 or —S(═O)2NR3— wherein R3 is
hydrogen or optionally substituted C1-C6
alkyl; L is a
divalent radical of formula -(Alk1)m(O)n(Alk2)p— wherein m, n and p are independently 0 or 1, Q is (i) an optionally substituted
divalent mono- or bicyclic carbocyclic or heterocyclic radical having 5-13 ring members, or (ii), in the case where both m and p are 0, a
divalent radical of formula —X2-Q1- or -Q1-X2— wherein X2 is —O—, S— or NRA— wherein RA is
hydrogen or optionally substituted C1-C3
alkyl, and Q1 is an optionally substituted divalent mono- or bicyclic carbocyclic or hetero-cyclic radical having 5-13 ring members, AIk1 and AIk2 independently represent optionally substituted divalent C3-C7 cycloalkyl radicals, or optionally substituted straight or branched, C1-C6 alkylene, C2-C6 alkenylene, or C2-C6 alkynylene radicals which may optionally contain or terminate in an
ether (—O—),
thioether (—S—) or amino (—NRA-) link wherein RA is
hydrogen or optionally substituted C1-C3
alkyl; X 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; z is 0 or 1; A represents an optionally substituted mono-, bi- or tri-cyclic carbocyclic or heterocyclic ring
system wherein the radicals R1R2NH—Y-L1-X1—[CH2]z— and HONHCO-[
LINKER]- are attached different ring atoms; and -[
Linker]- represents a divalent
linker radical linking a ring atom in A with the
hydroxamic acid group CONHOH, the length of the
linker radical, from the terminal atom linked to the ring atom of A to the terminal atom linked to the
hydroxamic acid group, is equivalent to that of an unbranched saturated
hydrocarbon chain of from 3-10 carbon atoms.