阿米福韦类似物及其前药的设计、合成与生物活性

Design,synthesis and biological activity of prodrugs of alamifovir analogs

目的对新型抗乙肝药物阿米福韦进行结构改造,设计合成新的前药。方法以2-氯乙醇为原料,经氯甲基化、取代、缩合、烃化、水解、缩合得到目标产物。结果合成了11个新结构化合物,并经1H-NMR、13C-NMR、MS确证结构。体外抗乙肝病毒活性测试结果显示,阿米福韦异丙基碳酸酯的抗病毒活性显著提高,为阿米福韦的100倍。结论阿米福韦碳酸酯能够更好的释放活性药物,提高抗病毒活性。

Aim To design and synthesize new alamifovir analogs prodrugs.Methods The target compounds were synthesized via chloromethylation,substitution,condensation,alkylation,hydrolization,condensation using 2-chloroethanol as starting material.Results 11 New compounds were synthesized and characterized with 1H-NMR,13C-NMR and MS.In vitro anti-HBV activity evaluation revealed that new alamifovir prodrug 1a is about 100 times more potent than alamifovir.Conclusion The anti-HBV activity of the new prodrug of alamifovir derivatives can be improved by releasing the active molecule more efficiently.