Succinic acid amides as P2-P3 replacements for inhibitors of interleukin-1beta converting enzyme (ICE or caspase 1)

Bioorganic & Medicinal Chemistry Letters
Paul GalatsisRobert Talanian

Abstract

Succinic acid amides have been found to be effective P2-P3 scaffold replacements for peptidic ICE inhibitors. Heteroarylalkyl fragments occupying the P4 position provided access to compounds with nM affinities. Utilization of an acylal prodrug moiety was required to overcome biopharmaceutical issues which led to the identification of 17f, a potential clinical candidate.

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Citations

Nov 10, 2015·Chemical Reviews·Marcin PorebaMarcin Drag
Aug 25, 2017·Organic & Biomolecular Chemistry·Y AdriaenssensP Van der Veken
Apr 15, 2015·Chemical Biology & Drug Design·Margaret KawarskiCaitlin E Karver
Apr 9, 2014·Angewandte Chemie·Maurizio BernasconiAndreas Pfaltz
May 14, 2021·Bioorganic & Medicinal Chemistry Letters·Yuanyuan ZhangHui Xu
Nov 1, 2011·Journal of the American Chemical Society·Xiao Wang, Stephen L Buchwald

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