PEPTIDYL DERIVATIVES AND THEIR USE AS METALLOPROTEINASES INHIBITORS

摘要

Compounds of formula (1) are described wherein R represents a -CONHOH, carboxyl (-CO2H), esterified carboxyl or -P(O)(X?1R8)X2R9¿ group, where X?1 and X2¿, which may be the same or different is each an oxygen or a sulphur atom, and R?8 and R9¿, which may be the same or different each represents a hydrogen atom or an optionally substituted alkyl, aryl or aralkyl group; R1 represents a hydrogen atom or an optionally substituted alkyl, alkenyl, aryl, aralkyl, heteroaralkyl or heteroarylthioalkyl group; R2 represents an optionally substituted aryloxy, arylthio, aryloxyalkyl, arylthioalkyl, heteroaryl, heteroaralkyl, heteroaryloxy, heteroarylthio, heteroaryloxyalkyl or heteroarylthioalkyl group; R3 represents a hydrogen atom or an alkyl group; R4 represents a hydrogen atom or an alkyl group; R5 represents an optionally substituted alkyl or alkenyl group optionally interrupted by one or more -O- or -S- atoms or -N(R7) groups, [where R7 is a hydrogen atom or a C¿1-6? alkyl group] or a group -[Alk]nR?6¿ where Alk is an alkyl or alkenyl group optionally interrupted by one or more -O- or -S- atoms or -N(R7) groups, n is zero or an integer 1 and R6 is an optionally substituted cycloalkyl or cycloalkenyl group; X represents an amino (-NH¿2?), or substituted amino, hydroxyl or substituted hydroxyl group; and the salts, solvates and hydrates thereof. The compounds are metalloproteinase inhibitors and in particular are selective inhibitors of the action of gelatinase, and may be of use in the treatment of cancer to control the development of tumour metastases.