全世界有3.5-4亿人为慢性乙型肝炎病毒 (HBV) 感染者，其中有约9300万的患者分布在我国。目前获得美国FDA所批准在临床使用的抗HBV药物有7种，其中有5种为核苷 (酸) 类化合物。然而，到目前为止还没有一种治疗手段可以治愈乙肝，当前已有的药物由于副作用和/或耐药性等原因也并不能满足临床治疗的需要。面对这样严峻的形势，开发药效好、副作用小且耐药性低的乙肝治疗新药意义重大。本项目在前期核苷类药物研发工作的基础上，设计并将合成一系列新型的4'-叠氮氟代（嘧啶/嘌呤）核苷类衍生物；通过对其抗HBV活性的筛选、构效关系的研究和进一步的优化，以寻找到具有开发前景的新型抗HBV核苷化合物。本项目的实施将为抗乙肝新药研发提供结构新颖的核苷类先导化合物，具有重要的学术价值和潜在的应用前景。

350-400 million people have been chronically infected with hepatitis B virus (HBV) worldwide, with about 93 million of these patients in China. So far, 7 anti-HBV drugs have been approved by US FDA for clinical use, with five of them being nucleos(t)ides. However, by now there is no cure for hepatitis B, and the current medicines still cannot meet clinical need due to their side effects and /or drug resistance. Therefore, development of new anti-HBV drugs with better efficacy, low side effects and low drug resistance rate is of great significance to the therapeutics of chronic hepatitis B. Built on our previous nucleoside drug development achievement, a series of novel 2'-deoxy-2'-fluoro-4'-azido (pyrimidine/purine) nucleoside derivatives were designed and will be synthesized in this project. Through anti-HBV activity screening, structure-activity relationship (SAR) investigation and further optimization of these nucleosides, new potential anti-HBV molecule(s) will be identified. With this project, our group is developing novel nucleoside lead compound(s) for further drug discovery and development, which is of important academic value and potential application prospect.