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Design, synthesis, and biological evaluation of new N(4)-Substituted 2'-deoxy-2'-fluoro-4'-azido cytidine derivatives as potent anti-HBV agents. 2015
Zhigang Lv, and
Wu He, and
Xianhai Tian, and
Jinfeng Kang, and
Yangxue Liu, and
Youmei Peng, and
Liyun Zheng, and
Qingduan Wang, and
Wenquan Yu, and
Junbiao Chang
College of Chemistry and Molecular Engineering, Zhengzhou University, Zhengzhou 450001, PR China.
A series of new 2'-deoxy-2'-β-fluoro-4'-azido-β-d-arabinofuranosyl cytidine derivatives bearing heteroatom-containing N(4)-substituents were designed and synthesized. Antiviral screening in HepG2.2.15 cells identified three analogs (1a, 1d &1g) with good anti-HBV activity and low cytotoxicty. Of them, compound 1g exhibited significant inhibitory activity on both HBV antigens secretion (EC50, HBsAg = 9 nM, EC50, HBeAg = 0.25 μM) and viral DNA replication (intracellular, EC50 = 0.099 μM; extracellular, EC50 < 0.01 μM).
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