新型核苷膦酸酯类化合物的合成及其抗乙肝病毒活性研究

Synthesis and anti-hepatitis B virus(HBV) activities of novel phosphonate nucleosides

目的设计合成新型核苷膦酸酯类化合物,并进行体外抗乙肝病毒活性评价。方法以不同取代的硫酚与2-氨基-9-[2-[二(2,2,2-三氟乙氧基)膦酰甲氧基]乙基]-6-氯嘌呤进行烃化反应合成目标化合物,化合物结构经1H-NMR和FAB-MS谱确证。采用HepG2.2215细胞进行体外抗乙肝病毒活性评价。结果与结论设计合成了9个核苷膦酸酯类新化合物,这些化合物均有一定的抗乙肝病毒活性。化合物4a、4b的活性强于拉米夫定、阿德福韦酯。苯环上取代基的类型显著影响核苷膦酸酯类化合物抗乙肝病毒活性。

Aim To design and synthesize novel phosphonate nuclcosides, and to evaluate their anti-hepatitis B virus activities in vitro. Methods The target compounds were synthesized by the alkylation of different subistituted thiophenols with 2-amino-6-chloro -9- [ 2-（phosphono methoxy） ethyl ] purine bis（2, 2,2-trifluo- roethyl） ester. All of the synthesized compounds were confirmed by 1H-NMR and FAB-MS. These compounds were tested to inhibit HBV in vitro with HepG2.2215 cells. Results and conclusion Nine target compounds that have been ＇never reported in the previous lectures were synthesized and exhibited potent anti-HBV activities to some extent. The compounds of 4a, 4b had higher potent anti-HBV activities than that of lamivudine and adefovir dipvoxil. The substitutent has an important influence on anti-hepatitis B virus activity of the title compounds.