Recent advances on the synthesis of hepatitis C virus NS5B RNA-dependent RNA-polymerase inhibitors.
Hepatitis C is a viral liver infection considered as the major cause of cirrhosis and hepatocellular carcinoma (HCC). The HCV NS5B polymerase, an RNA-dependent RNA polymerase, is essential for HCV replication, which is able to catalyze the synthesis of positive (genomic) and negative (template) strand HCV RNA, but has no functional equivalent in mammalian cells. Therefore, the NS5B polymerase has emerged as an attractive target for the development of specifically targeted antiviral therapy for HCV (DAA, for direct-acting antivirals). Recently, a growing number of compounds have been reported as the NS5B polymerase inhibitors, some of which especially have been licensed in clinical trials. This review describes recent advances on the synthesis of the NS5B polymerase inhibitors, focusing on the merits and demerits of their synthetic methods. In particular, inspiration from the synthesis and the future direction of the NS5B polymerase inhibitors are highlighted.
Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, Jinan 250012, PR China.
Can
C
Zhao
Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, Jinan 250012, PR China.
Yinhu
Y
Wang
Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, Jinan 250012, PR China. Electronic address: mashutao@sdu.edu.cn.
Shutao
S
Ma
D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D016174:Hepacivirus / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012324:RNA-Dependent RNA Polymerase
D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D017361:Viral Nonstructural Proteins; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase
Antiviral therapy; Biological activity; Hepatitis C; Inhibitors; NS5B polymerase; Synthesis