| abstract |
Compounds of the formula described, or an optical isomer, diastereomer or enantiomer thereof, or pharmaceutically acceptable salt, biohydrolyzable amide, ester, or imide thereof are useful as inhibitors of metalloproteases. Also disclosed are pharmaceutical compositions and methods of treating diseases, disorders and conditions characterised by metalloprotease activity using these compounds or the pharmaceutical compositions containing them. Wherein; R1 is H; R2 is hydrogen, alkyl or acyl; A is COR3 or SO2R4; and R3 is alkoxy, aryloxy, heteroaryloxy, alkyl, aryl, heteroaryl, heteroalkyl, amino, alkylamino, dialkylamino, arylamino and alkylarylamino; R4 is alkyl, heteroalkyl, aryl, or heteroaryl, substituted or unsubstituted; X is O, S, SO, SO2, or NR5, wherein R5 is independently chosen from hydrogen, alkyl, heteroalkyl, heteroaryl, aryl, SO2R6, COR7, CSR8, PO(R9)2 or may optionally form a ring with W;and R6 is alkyl, aryl, heteroaryl, heteroalkyl, amino, alkylamino, dialkylamino, arylamino, diarylamino and alkylarylamino; R7 is hydrogen, alkoxy, aryloxy, heteroaryloxy, alkyl, aryl, heteroaryl, heteroalkyl, amino, alkylamino, dialkylamino, arylamino and alkylarylamino; R8 is alkyl, aryl, heteroaryl, heteroalkyl, amino, alkylamino, dialkylamino, arylamino, diarylamino and alkylarylamino; R9 is alkyl, aryl, heteroaryl, heteroalkyl; W is hydrogen or one or more lower alkyl moieties, or is an alkylene, arylene, or heteroarylene bridge between two adjacent or nonadjacent carbons (thus forming a fused ring); Y is independently one or more of hydrogen, hydroxy, SR10, SOR4, SO2R4, alkoxy, amino, wherein amino is of formula NR11R12, wherein R11 and R12 are independently chosen from hydrogen, alkyl, heteroalkyl, heteroaryl, aryl, SO2R6, COR7, CSR8, PO(R9)2; and R10 is hydrogen, alkyl, aryl, heteroaryl; Z is nil, a spiro moiety or an oxo group substituted on the heterocyclic ring. |