Synthesis and evaluation of novel 1-(2-acylhydrazinocarbonyl)-cycloalkyl carboxamides as interleukin-1beta converting enzyme (ICE) inhibitors.
Basic Information
ID: ALA1146191
Journal: Bioorg Med Chem Lett
Title: Synthesis and evaluation of novel 1-(2-acylhydrazinocarbonyl)-cycloalkyl carboxamides as interleukin-1beta converting enzyme (ICE) inhibitors.
Authors: Soper DL, Sheville J, O'Neil SV, Wang Y, Laufersweiler MC, Oppong KA, Wos JA, Ellis CD, Fancher AN, Lu W, Suchanek MK, Wang RL, De B, Demuth TP.
Abstract: Novel 1-(2-acylhydrazinocarbonyl)cycloalkyl carboxamides were designed as peptidomimetic inhibitors of interleukin-1beta converting enzyme (ICE). A short synthesis was developed and moderately potent ICE inhibitors were identified (IC(50) values <100 nM). Most of the synthesized examples were selective for ICE versus the related cysteine proteases caspase-3 and caspase-8, although several dual-acting inhibitors of ICE and caspase-8 were identified. Several of the more potent ICE inhibitors were also shown to inhibit IL-1beta production in a whole cell assay (IC(50) < 500 nM).
CiteXplore: 16782334
DOI: 10.1016/j.bmcl.2006.05.076
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