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

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journal contribution
posted on 01.05.2017, 00:00 by Wenquan Yu, Ertong Li, Zhigang Lv, Ke Liu, Xiaohe Guo, Yuan Liu, Junbiao Chang
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 (EC50 = 0.39–1.1 μM) against the HCV genotype (GT) 1a, 1b, 2a, and 1b S282T replicons.