2-(8-氮杂-6-取代苯硫基-9H-嘌呤-9-基)乙氧基甲基磷酸类化合物的设计、合成及抗病毒活性  

Studies on synthesis and antiviral activities of a novel acyclic nucleoside phosphonates analogues on HBV

作　　者：邱晓敏[1] 刘嘉[1] 冯继禄[1] 牛春娟[1] 李科[1] 

机构地区：[1]第二军医大学药学院药物化学教研室,上海200433

出　　处：《药学实践杂志》2010年第4期299-303,共5页Journal of Pharmaceutical Practice

基　　金：上海市2004年度重大科技攻关项目(2004DZ19209)

摘　　要：目的设计、合成新型抗乙型肝炎病毒的开环核苷膦酸类似物。方法根据阿德福韦(PMEA)的结构特点,采用生物电子等排体理论,引入8-氮杂-6-取代苯硫基嘌呤,设计、合成系列目标化合物。化合物结构经IR,1H-NMR谱进行确证。对1 a-1 e化合物进行了体外抗HBsAg、HBeAg和抗HBV-DNA活性筛选试验。结果设计合成了10个目标化合物;所测化合物抗HBsAg、HBeAg活性均好于PMEA,化合物1 e抗HBV-DNA活性与PMEA相当,值得继续研究。结论PMEA引入8-氮杂-6-取代苯硫基嘌呤抗HBV-DNA活性保持,抗HBsAg、HBeAg活性提高。Objective To study of design and synthesis of the novel acyclic nucleoside phosphonates analogues and study their activities of inhibiting HBV. Methods Based on the chemical structure of PMEA, and according to the theory of bioisostere, a 8-aza-6-thiophenyl group was introduced and a series of title compounds were synthesized. All of them were confirmed by IR,1H-NMR and MS. Preliminary pharmacological test of Compounds 1a-1e was made on HBV. Results Ten compounds were synthesized. The test results show the inhibitory rate of la-le compounds on HBsAg and HBeAg is higher than PMEA. The inhibitory rate of compound le on HBV-DNA is correspond with PMEA. Conclusion The PMEA derivatives with a 8-aza-6-thiophenyl group have high activity on inhibiting HBsAg, HBeAg and HBV-DNA.

关 键 词：开环核苷膦酸类似物 化学合成 阿德福韦 抗乙肝病毒活性 

分 类 号：R914[医药卫生—药物化学]