Caspase inhibitors and uses thereof

摘要

This invention provides caspase inhibitors of formula I: wherein Z is oxygen or sulfur; R¹ is hydrogen, -CHN₂, R, CH₂OR, CH₂SR, or -CH₂Y; between R³ and R⁴ represents a single or double bond; Y is an electronegative leaving group; R² is CO₂H, CH₂CO₂H, or esters, amides or isosteres thereof; R³is a group capable of fitting into the S2 subsite of a caspase enzyme; R⁴ is a hydrogen or C_1-6 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.