The Bsmoc group as a novel scaffold for the design of irreversible inhibitors of cysteine proteases

Bioorganic & Medicinal Chemistry Letters
Jim IleyCláudio M Soares

Abstract

Carbamate and ester derivatives of the 1,1-dioxobenzo[b]thiophen-2-ylmethyloxycarbonyl (Bsmoc) scaffold react readily with thiols via a Michael addition at rates not significantly affected by the nature of the carboxylic or carbamic acid leaving group. These Michael acceptors are irreversible inhibitors of the cysteine proteases papain and human liver cathepsin B, displaying first-order kinetics with respect to inhibitor concentration. In contrast, none of the Bsmoc derivatives inhibited porcine pancreatic elastase, a serine protease.

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Citations

Mar 18, 2010·Chemical Communications : Chem Comm·Dyeison AntonowGiovanna Zinzalla
May 16, 2006·Bioorganic & Medicinal Chemistry Letters·Cláudia ValentePhilip J Rosenthal
Jun 6, 2009·Chemico-biological Interactions·Daniela M SantosCecília M P Rodrigues

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