Inhibition of interleukin-1β converting enzyme (ICE or caspase 1) by aspartyl acyloxyalkyl ketones and aspartyl amidooxyalkyl ketones

A series of acyloxyalkyl and amidooxyalkyl ketones appended to a carbobenzyloxy aspartic acid core have been prepared. The most potent of these new inhibitors was 4i with a Ki of 0.5 μM. These two series provide an improved understanding of the binding requirements for the hydrophobic prime side of ICE.

Acyloxyalkyl, 4, and amidooxyalkyl, 7, ketones based on aspartic acid have been prepared. These two series provide an improved understanding of the binding requirements for the hydrophobic prime side of ICE.Figure optionsDownload as PowerPoint slide