Cheng Cliff C, Huang Xiaohua, Shipps Gerald W, Wang Yu-Sen, Wyss Daniel F, Soucy Kyle A, Jiang Chuan-Kui, Agrawal Sony, Ferrari Eric, He Zhiqing, Huang H-C
Department of Lead Discovery Chemistry, Merck Research Laboratories, 320 Bent Street, Cambridge, Massachusetts 02141.
Department of Infectious Diseases, Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033.
ACS Med Chem Lett. 2010 Aug 17;1(9):466-71. doi: 10.1021/ml100128h. eCollection 2010 Dec 9.
Pyridine carboxamide-based inhibitors of the hepatitis C virus (HCV) NS5B polymerase were diversified and optimized to a variety of topologically related scaffolds. In particular, the 2-methyl nicotinic acid scaffold was developed into inhibitors with improved biochemical (IC50-GT1b = 0.014 μM) and cell-based HCV replicon potency (EC50-GT1b = 0.7 μM). Biophysical and biochemical characterization identified this novel series of compounds as palm site binders to HCV polymerase.
基于吡啶甲酰胺的丙型肝炎病毒（HCV）NS5B聚合酶抑制剂被多样化并优化成各种拓扑相关的骨架。特别是，2-甲基烟酸骨架被开发成具有改善的生化活性（IC50-GT1b = 0.014 μM）和基于细胞的HCV复制子活性（EC50-GT1b = 0.7 μM）的抑制剂。生物物理和生化特性鉴定表明，这一系列新型化合物是HCV聚合酶的棕榈位点结合剂。
