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.

Keywords: HCV antivirals; Nucleotide phosphoramidate prodrugs; Pyrimidine nucleoside analogs.