4'-叠氮基胞嘧啶核苷

1. Evolution of HCV NS5B Nucleoside and Nucleotide Inhibitors    HCV: The Journey from Discovery to a Cure    2019
Abstract:Adenosine and cytidine analogs containing the 2′-C-methyl substituent were identified as initial hits from screening. These compounds displayed selective anti-HCV activity in a cell-based HCV replicon assay and, as their triphosphates, inhibited HCV NS5B polymerase enzyme in a cell-free assay. Since then, a number of new 2′-modified nucleoside analogs and nucleotide derivatives were synthesized and evaluated for direct inhibition of HCV replication. Potency, selectivity, and other drug-like properties were substantially optimized, and consequently more than a dozen compounds were advanced into preclinical and clinical evaluations. In the end, a prodrug of 2′-fluoro-2′-C-methyluridine monophosphate PSI-7977 (GS-7977, sofosbuvir) was approved for the treatment of chronic HCV infection.
2.Specific targeted antiviral therapy for hepatitis C    Current Gastroenterology Reports    2007    
Abstract:Since the discovery of the hepatitis C virus (HCV) as the major cause of non-A, non-B hepatitis in 1989, the search for specific targeted antiviral therapy for HCV (STAT-C) has been underway. Recently, major advances in the understanding of HCV biology and the development of an in vitro system of HCV replication have contributed to the selection of multiple candidate drugs for the treatment of hepatitis C. In 2006, five such candidate drugs have entered phase II clinical trials in patients chronically infected with hepatitis C, including small molecule inhibitors of the HCV NS3 serine protease and NS5B RNA-dependent RNA polymerase. This review focuses on hepatitis C protease and polymerase inhibitors that have progressed to phase II clinical development, foreshadowing the era of STAT-Cs.