Wang Shuni, Wang Yibing, Wang Jiang, Sato Tatsunori, Izawa Kunisuke, Soloshonok Vadim A, Liu Hong
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203, China.
Hamari Chemicals Ltd., 1-4-29 Kunijima, Higashi-Yodogawa-ku, Osaka 533-0024, Japan.
Curr Pharm Des. 2017;23(30):4493-4554. doi: 10.2174/1381612823666170522122424.
Hepatitis C is a current pandemic liver disease caused by the hepatitis C virus (HCV) with high morbidity and mortality. Recently, the direct-acting antiviral agents (DAAs) targeting HCV NS3/4A, NS5A and NS5B have become the most effective therapies against HCV infection in the clinical treatment. Among them, the second-generation of NS3/4A inhibitors have emerged as the mainstay of the DAA therapies, which are derived from the peptide substrate of NS3/4A protease and modified with various tailor-made amino acids in order to achieve high sustained virologic response (SVR) against HCV. This review summarizes sixteen examples of the second-generation of HCV NS3/4A inhibitors, mainly focusing on the clinical application, structure development, structure-activity relationship (SAR) and their synthesis.
丙型肝炎是由丙型肝炎病毒（HCV）引起的一种当前流行的肝脏疾病，具有高发病率和死亡率。最近，靶向HCV NS3/4A、NS5A和NS5B的直接抗病毒药物（DAAs）已成为临床治疗中对抗HCV感染最有效的疗法。其中，第二代NS3/4A抑制剂已成为DAA疗法的中流砥柱，它们源自NS3/4A蛋白酶的肽底物，并通过各种定制氨基酸进行修饰，以实现对HCV的高持续病毒学应答（SVR）。本综述总结了第二代HCV NS3/4A抑制剂的十六个实例，主要侧重于临床应用、结构开发、构效关系（SAR）及其合成。
