Design, synthesis, and biological evaluation of new N4-Substituted 2′-deoxy-2′-fluoro-4′-azido cytidine derivatives as potent anti-HBV agents
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Add time:08/01/2019 Source:sciencedirect.com
A series of new 2′-deoxy-2′-β-fluoro-4′-azido-β-d-arabinofuranosyl cytidine derivatives bearing heteroatom-containing N4-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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