Synthesis and evaluation of novel 1-(2-acylhydrazinocarbonyl)-cycloalkyl carboxamides as interleukin-1beta converting enzyme (ICE) inhibitors.

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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 Jr

Synthesis and evaluation of novel 1-(2-acylhydrazinocarbonyl)-cycloalkyl carboxamides as interleukin-1beta converting enzyme (ICE) inhibitors.

Bioorg Med Chem Lett. 2006 Aug 15;16(16):4233-6. Epub 2006 Jun 16.

PubMed ID

16782334 [ View in PubMed

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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).

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Pralnacasan	Caspase-1	IC 50 (nM)	3.6	N/A	N/A	Details