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

Bioorg Med Chem Lett. 2010 Sep 1;20(17):5089-94. doi: 10.1016/j.bmcl.2010.07.031. Epub 2010 Jul 11.

Abstract

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 K(i) of 0.5 microM. These two series provide an improved understanding of the binding requirements for the hydrophobic prime side of ICE.

MeSH terms

  • Caspase Inhibitors*
  • Cysteine Proteinase Inhibitors / pharmacology*
  • Humans
  • Ketones / pharmacology*
  • Models, Molecular
  • Monocytes / drug effects

Substances

  • Caspase Inhibitors
  • Cysteine Proteinase Inhibitors
  • Ketones