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 Strastes

Bioorganic & Medicinal Chemistry Letters（1997）

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摘要

Aryl-substituted tetronic acids, tetramic acids, and cyclic β-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 (kobs[I] 100,000–250,000 M−1s−1) of the cysteine protease ICE.

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