| Abstract |
ABSTRACT Compounds of formula (I) are inhibitors of histone deacetytase activity, and are useful in the treatment of, for example, cancers:: wherein R1 is a carboxyclic acid group (-COOH), or an ester group which is hydroysable 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)r, -C{=O)O. –C(=O)NR3, -C(=S)-NR3, -C(=NI)NR3 or -S(=O)2NR3- wherein R3 is hydrogen or optionally substituted C1-C6 alkyl; L1 is a divalent radical of formula -(Alk1)m(Q)4Ak2 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, alkyl Q1 is an optionally substituted divalent mono- or bicyclic carbocycfic or heterocyclic radical having 5-13 ring members, Alk1 and Alk2 independently represent optionally substituted divalent C3-C7 cycloalkyl radicals, or optionally substituted straight or txanched, C1-C6 alkyiene, C2-C6 alkenylene ,or C2-C6 alkynylene radicals which may optionally contain or terminate in an ether (-O), thioether (-S-) or amino (-NR^-) Br* wherein RA is hydrogen or optionally substituted C1-C6 alkyl; Xhx*" represents a txxid; -C(=O); or -S(=O)2-; -NR4C(=OV, -C(=O)NR4-,-NR4C(=O)NR5-, -NR^S(=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 cartocyclic or heterocyclic ring system wherein the radicals R1R2NH-Y-L1-XV1; and HONHGCOLINKER]- 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 hydroxamk acid group, is equivalent to that of an unbranched saturated hydrocarbon chain of from 3-10 carbon atoms. |