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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. 2017
Wenquan Yu, and
Ertong Li, and
Zhigang Lv, and
Ke Liu, and
Xiaohe Guo, and
Yuan Liu, and
Junbiao Chang
College of Chemistry and Molecular Engineering, Zhengzhou University, Zhengzhou, Henan 450001, P. R. China.
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.
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