Anadys Pharmaceuticals, Inc., 3115 Merryfield Row, San Diego, CA 92121, USA.
Bioorg Med Chem Lett. 2009 Nov 1;19(21):6047-52. doi: 10.1016/j.bmcl.2009.09.051. Epub 2009 Sep 17.
The discovery of 5,5'- and 6,6'-dialkyl-5,6-dihydro-1H-pyridin-2-ones as potent inhibitors of the HCV RNA-dependent RNA polymerase (NS5B) is described. Several of these agents also display potent antiviral activity in cell culture experiments (EC50 <0.10 microM). In vitro DMPK data for selected compounds as well as crystal structures of representative inhibitors complexed with the NS5B protein are also disclosed.
描述了 5,5'- 和 6,6'-二烷基-5,6-二氢-1H-吡啶-2-酮作为 HCV RNA 依赖性 RNA 聚合酶 (NS5B) 的有效抑制剂的发现。这些试剂中的一些在细胞培养实验中也显示出很强的抗病毒活性（EC50 <0.10 microM）。还披露了选定化合物的体外 DMPK 数据以及代表性抑制剂与 NS5B 蛋白结合的晶体结构。
