Novel drugs are urgently needed to combat hepatitis B virus (HBV) infection due to drug-resistant virus. In this paper, a series of novel 4-monosubstituted 2′-deoxy-2′-β-fluoro-4′-azido-β-d-arabinofuranosyl 1,2,3-triazole nucleoside analogues (1a-g) were designed, synthesized and screened for in vitro anti-HBV activity. At 5.0 μM in the cellular model, all the synthetic compounds display activities comparable to that of the positive control, lamivudine at 20 μM. Of the compounds tested, the amide-substituted analogue (1a) shows the most promising anti-HBV activity and low cytotoxicity in the cell model. In particular, it retains excellent activity against lamivudine-resistant HBV mutants. In duck HBV (DHBV)-infected duck models, both the serum and liver DHBV DNA levels (67.4% and 53.3%, respectively) were reduced markedly by the treatment with 1a. Analysis of the structure of HBV polymer/1a-triphosphate (1a-TP) complex shows that 1a-TP is stabilized by specific van der Waals interactions with the enzyme residues arising from 4-amino-1,2,3-triazole and the 4′-azido group.

由于抗药性病毒，迫切需要新型药物来对抗乙型肝炎病毒（HBV）感染。本文设计了一系列新颖的4-单取代的2'-脱氧-2'-β-氟-4'-叠氮基-β- d-阿拉伯呋喃糖基1,2,3-三唑核苷类似物（1a-g），合成并筛选体外抗HBV活性。在5.0  μ M在蜂窝模式下，所有的合成化合物显示比得上阳性对照，拉米夫定在20活动 μ M的化合物测试，酰胺-取代的类似物（1A）在细胞模型中显示出最有希望的抗HBV活性和低细胞毒性。特别是，它对抗拉米夫定的HBV突变体具有出色的活性。在鸭HBV（DHBV）感染的鸭模型中，用1a处理可显着降低血清和肝脏DHBV DNA水平（分别为67.4％和53.3％）。HBV聚合物/ 1a-三磷酸酯（1a-TP）配合物的结构分析表明，1a-TP通过与4-氨基-1,2,3-三唑和4-氨基苯甲酸产生的酶残基的特异性范德华相互作用而稳定。 '-叠氮基团。