Caspase inhibitors and uses thereof

摘要

This invention provides compounds of formula I: wherein Z is oxygen or sulfur; R1 is hydrogen, -CHN2, R, CH2OR, CH2SR, or -CH2Y; <custom-character file="US20030092703A1-20030515-P00900.TIF" wi="20" he="20" id="custom-character-00001"/>next to R3 represents a single or double bond; Y is an electronegative leaving group; R2 is CO2H, CH2CO2H, or esters, amides or isosteres thereof; R3 is a group capable of fitting into the S2 subsite of a caspase enzyme; R4 is a hydrogen or C1-6 alkyl or R3 and R4 taken together form a ring; Ring A and Ring B are each heterocyclic rings, and R and R5 are as described in the specification. The compounds are effective inhibitors of apoptosis and IL-1beta secretion.