Design, synthesis, and biological evaluation of new N-4-Substituted 2 '-deoxy-2 '-fluoro-4 '-azido cytidine derivatives as potent anti-HBV agents

作者：Lv, Zhigang; He, Wu; Tian, Xianhai; Kang, Jinfeng; Liu, Yangxue; Peng, Youmei; Zheng, Liyun; Wang, Qingduan; Yu, Wenquan^*; Chang, Junbiao

来源：European Journal of Medicinal Chemistry, 2015, 101: 103-110.

DOI：10.1016/j.ejmech.2015.06.030

• 2 '-deoxy-2 '-beta-fluoro-4 '-azido-beta-D-arabinofuranosyl cytidines
• N-4-substituted
• Anti-HBV activity
• HBV antigens
• Viral DNA replication

A series of new 2'-deoxy-2'-beta-fluoro-4'-azido-B-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 HM, EC50, HBeAg = 0.25 mu M) and viral DNA replication (intracellular, EC50 = 0.099 mu M; extracellular, EC50 < 0.01 mu M).

• 出版日期2015-8-28
• 单位郑州大学; 河南省医药科学研究院