Synthesis and Anti-HCV Activity of a Novel 2',3'-Dideoxy-2'-α-fluoro-2'-ß-C-methyl Guanosine Phosphoramidate Prodrug.

A novel 2',3'-dideoxy-2'-α-fluoro-2'-ß-C-methyl-6-methoxy guanosine (8) and its phosphoramidate prodrug (1) have been designed and synthesized. Their biological activity was evaluated in both cytotoxicity and cell-based HCV replicon assays. Neither compounds exhibited cytotoxicity up to the highest concentration tested (100 µM) in the Huh-7 cell line. The prodrug (1) displayed nanomolar level antiviral activity (EC50 = 0.39-1.1 µM) against the HCV genotype (GT) 1a, 1b, 2a, and 1b S282T replicons.