Synthesis and evaluation of diacylhydrazines as inhibitors of the interleukin-1β converting enzyme (ICE)

Diacylhydrazines ([azaAsp1] derivatives) were prepared and shown to inactivate ICE in a time-dependent manner. Inactivation rates for most of these diacylhydrazines were 10-fold slower than their α-substituted methylketone congeners. Rates for 6 and 7 (ca. 18,000 M−1s−1) compared favorably to those reported for Ac-Tyr-Val-Ala-Asp-CH-N2 and azapeptide inhibitors for other cysteine proteases.