Inhibitors of hepatitis C virus NS3· 4A protease. Effect of P4 capping groups on inhibitory potency and pharmacokinetics

RB Perni, G Chandorkar, KM Cottrell, CA Gates…

Index: Perni, Robert B.; Chandorkar, Gurudatt; Cottrell, Kevin M.; Gates, Cynthia A.; Lin, Chao; Lin, Kai; Luong, Yu-Ping; Maxwell, John P.; Murcko, Mark A.; Pitlik, Janos; Rao, Govinda; Schairer, Wayne C.; Drie, John Van; Wei, Yunyi Bioorganic and Medicinal Chemistry Letters, 2007 , vol. 17, # 12 p. 3406 - 3411

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Citation Number: 30

Abstract

Reversible tetrapeptide-based compounds have been shown to effectively inhibit the hepatitis C virus NS3· 4A protease. Inhibition of viral replicon RNA production in Huh-7 cells has also been demonstrated. We show herein that the inclusion of hydrogen bond donors on the P4 capping group of tetrapeptide-based inhibitors result in increased binding potency to the NS3· 4A protease. The capping groups also impart significant effects on the ...