David J. Lauffer

The synthesis and evaluation of peptidyl aspartyl aldehydes as inhibitors of ice.

Abstract The tetrapeptide aldehyde Ac-Tyr-Val-Ala-AspH ( 1 , L-709,049) has been reported to be a potent reversible inhibitor of Interleukin-1β Converting Enzyme (ICE). We have prepared a series of analogs of 1 , in order to explore the active sige of ICE. The effects of truncation, methylation of the amide nitrogens and modification of the aldehyde group of 1 are presented.

3-Aryl-4-(arylhydrazono)-1H-pyrazol-5-ones: Highly ligand efficient and potent inhibitors of GSK3beta.

A series of 3-aryl-4-(arylhydrazono)-1H-pyrazol-5-one inhibitors of GSK3beta was developed from a low molecular weight, highly ligand efficient screening hit 1. Hit-to-lead optimization led to a number of highly potent inhibitors, while maintaining the high ligand efficiency of the screening hit.

A practical synthesis of (S) 3-tert-Butoxycarbonylamino-2-oxo-2,3,4,5-tetrahydro-1,5-benzodiazepine-1-acetic acid methyl ester as a conformationally restricted dipeptido-Mimetic for caspase-1 (ICE) inhibitors

A simple and versatile method for the synthesis of (S) 3-tert-butoxycarbonylamino-2-oxo-2,3,4,5-tetrahydro-1,5-benzodiazepine-1-acetic acid methyl ester (4), a dipeptide mimetic, has been developed. The regioselective functionalization of the N1 and N5 ring nitrogens and the C3 amino group is demonstrated in the synthesis of an interleukin-1beta converting enzyme inhibitor 13.