| 摘要 |
2139129 9425435 PCTABS00034 Compounds of formula (1), wherein R represents a -CONHOR6 ¢where R6 is a hydrogen atom or an acyl group!, carboxyl (-CO2H), esterified carboxyl, -SR6 or -P(O)(X1R7)-X2R8 group, where X1 and X2, which may be the same or different, is each an oxygen or sulphur atom and R7 and R8, 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 alkyl, alkenyl, cycloalkyl, cycloalkylalkyl, aryl, amino (-NH2), substituted amino, carboxyl (-CO2H), or esterified carboxyl group; R3 represents a hydrogen atom or an alkyl group; R4 represents a hydrogen atom or an alkyl group; R5 represents a group -C(R9)(R10)Het-R11, wherein R9 and R10 which may be the same or different is each an optionally substituted alkyl or alkenyl group optionally interrupted by one or more -O- or -S- atoms or -N(R12)- groups (where R12 is a hydrogen atom or an optionally substituted alkyl group), or an optionally substituted cycloalkyl, cycloalkenyl, aryl or heteroaryl group, or R9 and R10 together with the carbon atom to which they are attached are linked together to form an optionally substituted cycloalkyl or cycloalkenyl group, Het is -O-, -S(O)p- ¢where p is zero, or an integer 1 or 2! or -N(R12)-, and R11 is a hydrogen atom or an aliphatic, cycloaliphatic, heterocycloaliphatic, aromatic, or heteroaromatic group; X is an amino (-NH2), substituted amino, hydroxyl or substituted hydroxyl group, or is linked to the atom or group Het in R5 to form a chain -X-Alk-R5- where X is -N(R12)-, Alk is an optionally substituted alkylene chain and R5 is -Het-C(R9)(R10)-; and the salts, solvates, hydrates and prodrugs thereof. The compounds are orally active metalloproteinase inhibitors, with a good duration of action and may be of use in the prophylaxis or treatment of diseases or disorders in which stromelysin, collagenase and gelatinase have a role, for example in the treatment of cancer to control the development of tumor metastases.
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