Highly potent non-peptidic inhibitors of the HCV NS3/NS4A serine protease
D Sperandio, AR Gangloff, J Litvak, R Goldsmith…
文献索引：Sperandio, David; Gangloff, Anthony R.; Litvak, Joane; Goldsmith, Richard; Hataye, Jason M.; Wang, Vivian R.; Shelton, Emma J.; Elrod, Kyle; Janc, James W.; Clark, James M.; Rice, Ken; Weinheimer, Steve; Yeung, Kap-Sun; Meanwell, Nicholas A.; Hernandez, Dennis; Staab, Andrew J.; Venables, Brian L.; Spencer, Jeffrey R. Bioorganic and Medicinal Chemistry Letters, 2002 , vol. 12, # 21 p. 3129 - 3133
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 Zn2+-dependent inhibitor (1). Optimization of this screening hit afforded a 10-fold more potent inhibitor (46) under Zn2+ conditions (Ki= 27nM). This compound (46) binds also to NS3/NS4A in a Zn2+ independent fashion (Ki= 1μM). The SAR of this class of compounds under Zn2+ conditions is highly ...
