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

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*Hong Liu*

Affiliation:

• Hamari Chemicals Ltd., 1-4-29 Kunijima, Higashi-Yodogawa-ku, Osaka 533-0024,Japan

• IKERBASQUE, Basque Foundation for Science, Alameda Urquijo 36-5, Plaza Bizkaia, 48011 Bilbao,Spain

• CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203,China

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.

Cite this article as:

Wang Shuni , Wang Yibing, Wang Jiang, Sato Tatsunori, Izawa Kunisuke *, Soloshonok A. Vadim*, Liu Hong*, 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 2017; 23 (30) . https://dx.doi.org/10.2174/1381612823666170522122424