Synthesis And Anti-Hcv Activity Of A Novel 2,' 3 '-Dideoxy-2 '-Alpha-Fluoro-2 '-Beta-C-Methyl Guanosine Phosphoramidate Prodrug

A novel 2',3'-dideoxy-2'-alpha-fluoro-2'-beta-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 mu M) in the Huh-7 cell line. The prodrug (1) displayed nanomolar level antiviral activity (EC50 = 0.39-1.1 mu M) against the HCV genotype (GT) la, lb, 2a, and lb S282T replicons.