Caspase inhibitors and uses thereof

A compound of formula Ia:

• or a pharmaceutically-acceptable derivative thereof,
• wherein:
• next to R3 represents a single or double bond;
• Z is oxygen or sulfur;
• R1 is CH2Y;
• Y is an electronegative leaving group;
• R2 is CO2H, CH2CO2H, or esters, amides or isosteres thereof;
• R3 is hydrogen, a side chain of a natural α-amino acid, or a substituted or unsubstituted group having a molecular weight up to about 140 Daltons selected from C1-12 aliphatic, 5-14 membered aryl, (5-14 membered aryl)-(C1-12-alkyl)-, 3-9 membered heterocyclyl, or (3-9 membered heterocyclyl)-(C1-12-alkyl)-;
• wherein said R3 is optionally substituted with halogen, —R, —OR, —OH, —SH, —SR, acyloxy, phenyl (Ph), —OPh, —NO2, —CN, —NH2, —NHR, —N(R)2, —NHCOR, —NHCONHR, —NHCON(R)2, —NRCOR, —NHCO2R, —CO2R, —CO2H, —COR, —CONHR, —CON(R)2, —S(O)2R, —SONH2, —S(O)R, —SO2NHR, —NHS(O)2R, ═O, ═S, ═NNHR, ═NNR2, ═N—OR, ═NNHCOR, ═NNHCO2R, ═NNHSO2R, or ═NR;
• R is C1-6 aliphatic;
• R4 is hydrogen or a C1-6 aliphatic group that is optionally interrupted by —O—, —S—, —SO2—, —CO—, —NH—, or —N(C1-4 alkyl)-, or R3 and R4 taken together with their intervening atoms optionally form a 3-7 membered ring having 0-2 heteroatoms selected from nitrogen, oxygen or sulfur;
• Ring A is a nitrogen-containing mono-, bi- or tricyclic ring system having 0-5 additional ring heteroatoms selected from nitrogen, oxygen or sulfur provided that Ring A is not carbazole.