Document Report Card

Basic Information

ID: ALA1134940

Journal: Bioorg Med Chem Lett

Title: Highly potent non-peptidic inhibitors of the HCV NS3/NS4A serine protease.

Authors: Sperandio D, Gangloff AR, Litvak J, Goldsmith R, Hataye JM, Wang VR, Shelton EJ, Elrod K, Janc JW, Clark JM, Rice K, Weinheimer S, Yeung KS, Meanwell NA, Hernandez D, Staab AJ, Venables BL, Spencer JR.

Abstract: Screening of a diverse set of bisbenzimidazoles for inhibition of the hepatitis C virus (HCV) serine protease NS3/NS4A led to the identification of a potent Zn(2+)-dependent inhibitor (1). Optimization of this screening hit afforded a 10-fold more potent inhibitor (46) under Zn(2+) conditions (K(i)=27nM). This compound (46) binds also to NS3/NS4A in a Zn(2+) independent fashion (K(i)=1microM). The SAR of this class of compounds under Zn(2+) conditions is highly divergent compared to the SAR in the absence of Zn(2+), suggesting two distinct binding modes.

CiteXplore: 12372517

DOI: 10.1016/s0960-894x(02)00680-7