α-((Tetronoyl)oxy)- and α-((tetramoyl)oxy)methyl ketone inhibitors of the interleukin-1β converting enzyme (ICE)

Todd L. Graybill, Catherine P. Prouty, Gary J. Speier, Denton Hoyer, Roland E. Dolle, Carla T. Helaszek, Mark A. Ator, Joanne Uhl, Joost Strasters

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Aryl-substituted tetronic acids, tetramic acids, and cyclic P-dicarbonyl moieties were evaluated as leaving groups in the peptidyl-COCH2-X type inhibitor iii. Tripeptidyl aspartyl α-((tetronoyl)oxy)- and α-((tetramoyl)oxy)methyl ketone derivatives demonstrate potent time-dependent inhibition (k(obs)/[I] 100,000-250,000 M-1 s-1) of the cysteine protease ICE.

Original languageEnglish
Pages (from-to)41-46
Number of pages6
JournalBioorganic and Medicinal Chemistry Letters
Volume7
Issue number1
DOIs
StatePublished - Jan 7 1997

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