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A novel 2',3'-dideoxy-2'-α-fluoro-2'-β- 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 (EC 50 = 0.39-1.1 μM) against the HCV genotype (GT) 1a, 1b, 2a, and 1b S282T replicons.

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