Evolution, synthesis and SAR of tripeptide alpha-ketoacid inhibitors of the hepatitis C virus NS3/NS4A serine protease.

Stefania Colarusso, Benjamin Gerlach, Uwe Koch, Ester Muraglia, Immacolata Conte, Ian Stansfield, Victor G Matassa, Frank Narjes

Index: Bioorg. Med. Chem. Lett. 12(4) , 705-8, (2002)

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Abstract

N-terminal truncation of the hexapeptide ketoacid 1 gave rise to potent tripeptide inhibitors of the hepatitis C virus NS3 protease/NS4A cofactor complex. Optimization of these tripeptides led to ketoacid 30 with an IC50 of 0.38 microM. The SAR of these tripeptides is discussed in the light of the recently published crystal structures of a ternary tripetide/NS3/NS4A complexes.