1H-1,2,3-三氮唑乙酸酯衍生物的合成与体外抗乙肝病毒活性研究

1H-1,2,3-Triazol-1-yl acetate derivatives and in vitro anti-HBV activity

目的设计合成1H-1,2,3-三氮唑环衍生物,并测定其体外抗乙肝病毒活性。方法以取代吲哚为原料,经取代、环加成反应得到14个目标化合物,通过^(1)H-NMR、^(13)C-NMR和MS方法对化合物的结构进行表征,以HepG2.2.15为细胞模型进行抗乙肝病毒体外活性实验,测试化合物在体外对乙肝病毒e抗原(HBeAg)和乙肝病毒表面抗原(HBsAg)分泌的影响。结果与结论其中4个目标化合物能较好地抑制HBeAg和HBsAg的分泌,化合物2-(4-((5-氯-1H-吲哚-1-基)甲基)-1H-1,2,3-三唑-1-基)乙酸乙酯(IC_(50)=75.41μmol·L^(-1),SI=9.23)能较好抑制HBV DNA。吲哚5号位含有吸电子基团卤素原子的化合物对抑制乙肝病毒的分泌效果较好。

1H-1,2,3-Triazole ring derivatives were designed and synthesized from indole,and measured for anti-HBV activity in vitro.Fourteen target compounds were obtained from substituted indoles by substitution and cycloaddition reaction.The structures of the compounds were characterized by^(1)H-NMR,^(13)C-NMR and MS methods.HepG2.2.15 was used as a cell model to test the anti-HBV activity in vitro,and the effects of the compound on the secretion of hepatitis B surface antigen(HBsAg)and hepatitis B e antigen(HBeAg)in vitro were tested.Compounds 3c,3d,3m and 3n can inhibit the secretion of HBeAg and HBsAg.Meanwhile,compound 2-(4-((5-chloro-1H-indol-1-yl)methyl)-1 H-1,2,3-triazol-1-yl)ethyl acetate(IC_(50)=75.41μmol·L^(-1),SI=9.23)can better inhibit HBV DNA than other compounds synthesized.The indole 5-position halogen atom had obvious effect on inhibiting the secretion HBV.