AbbVie, Department R4AJ, Building AP52N, 1 North Waukegan Road, North Chicago, IL 60064, United States.
Bioorg Med Chem Lett. 2013 Aug 1;23(15):4367-9. doi: 10.1016/j.bmcl.2013.05.078. Epub 2013 Jun 4.
Described herein is the development of a potent non-nucleoside, small molecule inhibitor of genotype 1 HCV NS5B Polymerase. A 23 μM inhibitor that was active against HCV polymerase was further elaborated into a potent single-digit nanomolar inhibitor of HCV NS5B polymerase by additional manipulation of the R and R1 substituents. Subsequent modifications to improve physical properties were made in an attempt to achieve an acceptable pharmacokinetic profile.
本文描述了一种有效的非核苷、小分子 HCV 基因型 1 NS5B 聚合酶抑制剂的开发。进一步对 23μM 的 HCV 聚合酶抑制剂进行了修饰，通过对 R 和 R1 取代基的进一步修饰，得到了一种对 HCV NS5B 聚合酶具有高效活性的单个位数纳摩尔抑制剂。为了达到可接受的药代动力学特征，随后进行了改善物理性质的修饰。
