Title:The Second-generation of Highly Potent Hepatitis C Virus (HCV) NS3/4A Protease Inhibitors: Evolutionary Design Based on Tailor-made Amino Acids, Synthesis and Major Features of Bio-activity
VOLUME: 23 ISSUE: 30
Author(s):Shuni Wang, Yibing Wang, Jiang Wang, Tatsunori Sato, Kunisuke Izawa*, Vadim A. Soloshonok* and Hong Liu*
Affiliation:State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203, Hamari Chemicals Ltd., 1-4-29 Kunijima, Higashi-Yodogawa-ku, Osaka 533-0024, Hamari Chemicals Ltd., 1-4-29 Kunijima, Higashi-Yodogawa-ku, Osaka 533-0024, IKERBASQUE, Basque Foundation for Science, Alameda Urquijo 36-5, Plaza Bizkaia, 48011 Bilbao, CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203
Keywords:Hepatitis C virus (HCV), pandemic, direct-acting antiviral agents (DAAs), NS3/4A protease inhibitor, tailor-made amino acids,
structure-activity relationship (SAR), asymmetric synthesis, ring-closing metathesis (RCM).
Abstract: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.
