4’-Modified Pyrimidine Nucleosides as Potential Anti-hepatitis C Virus (HCV) Agents

Herein, we have investigated novel pyrimidine nucleosides bearing a 4’-carboxyl functionality (6-10, 13 and 15) as anti-HCV agents. In this new class of compounds, 7, 9, 10 and 15 demonstrated in vitro anti-HCV activity similar to or better than a known anti-HCV drug, ribavirin. In this work, we also, surprisingly, identified a 3’-sulfoxide analog of 3’-thiacytidine (16), obtained as a side product during the synthesis of 15, as a potent inhibitor of HCV replication at the concentration similar to that of ribavirin. No detectable in vitro cytotoxicity was observed for the investigated compounds up to the highest concentration tested.