Synthesis and characterization of 1′-C-cyano-2′-fluoro-2′-C-methyl pyrimidine nucleosides as HCV polymerase inhibitors

Abstract The first synthesis of 1′- C -CN, 2′-F, 2′- C -Me pyrimidines is described. Anti-HCV activity was assessed and compared to the 1′- C -CN, 2′- C -Me as well as the 2′-F, 2′- C -Me pyrimidines. A phosphoramidate prodrug of the cytidine derivative showed activity in the low micromolar range against HCV replicons.