Discovery of pyrimidine nucleoside dual prodrugs and pyrazine nucleosides as novel anti-HCV agents.
Basic Information
ID: ALA4411327
Journal: Bioorg Med Chem
Title: Discovery of pyrimidine nucleoside dual prodrugs and pyrazine nucleosides as novel anti-HCV agents.
Authors: Guo S, Xu M, Guo Q, Zhu F, Jiang X, Xie Y, Shen J.
Abstract: To explore the application potential of dual prodrug strategies in the development of anti-HCV agents, a variety of sofosbuvir derivatives with modifications at the C4 or N3 position of the uracil moiety were designed and synthesized. Some compounds exhibited potent anti-HCV activities, such as 4e and 8a-8c with similar EC50 values (0.20-0.22 μM) comparative to that of sofosbuvir (EC50 = 0.18 μM) in a genotype 1b based replicon Huh-7 cell line. Moreover, 8b displayed a good human plasma stability profile, and was easily metabolized in human liver microsomes expectantly. On the other hand, aiming to discover novel anti-HCV nucleosides, pyrazin-2(1H)-one nucleosides and their phosphoramidate prodrugs were investigated. Several active compounds were discovered, such as 25e (EC50 = 7.3 μM) and S-29b (EC50 = 19.5 μM). This kind of nucleosides were interesting and would open a new avenue for the development of antiviral agents.
CiteXplore: 30683552
DOI: 10.1016/j.bmc.2019.01.007
Patent ID: ┄