Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA.
Bioorg Med Chem Lett. 2013 Dec 15;23(24):6585-7. doi: 10.1016/j.bmcl.2013.10.060. Epub 2013 Nov 6.
The discovery of lead compound 2e was described. Its covalent binding to HCV NS5B polymerase enzyme was investigated by X-ray analysis. The results of distribution, metabolism and pharmacokinetics were reported. Compound 2e was demonstrated to be potent (replicon GT-1b EC50 = 0.003 μM), highly selective, and safe in in vitro and in vivo assays.
本文描述了先导化合物 2e 的发现。通过 X 射线分析研究了其与 HCV NS5B 聚合酶的共价结合。报告了分布、代谢和药代动力学的结果。在体外和体内试验中，化合物 2e 表现出强效（复制子 GT-1b EC50 = 0.003 μM）、高度选择性和安全性。
