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

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.