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

Current Pharmaceutical Design
Shuni WangHong Liu

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.

Citations

Jan 10, 2018·World Journal of Hepatology·Reza Taherkhani, Fatemeh Farshadpour
Apr 20, 2019·Medicinal Research Reviews·Xiangyi JiangPeng Zhan
Dec 15, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Jianlin HanVadim A Soloshonok
May 18, 2019·Chemistry : a European Journal·Haibo MeiVadim A Soloshonok
May 3, 2020·Chemistry : a European Journal·Haibo MeiVadim A Soloshonok
Nov 20, 2019·European Journal of Medicinal Chemistry·Haibo MeiVadim A Soloshonok
Sep 24, 2020·European Journal of Medicinal Chemistry·Jiang LiuVadim A Soloshonok
Apr 28, 2021·European Journal of Medicinal Chemistry·Jianlin HanKunisuke Izawa

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