5-取代嘧啶开环核苷膦酸酯类化合物的合成及其抗病毒活性研究
Studies on synthesis and antiviral activities of 5-substituted pyrimidine acyclic nucleoside phosphonate compounds on HBV
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摘要: 目的:设计合成5-取代嘧啶开环核苷膦酸酯类新化合物并进行体外抗病毒活性实验。方法:氯甲基氯乙基醚与三氟乙醇磷酸酯缩合后,经碘-氯交换得碘代乙氧基甲基三氟乙醇膦酸酯侧链,和5-取代嘧啶在DBU作用下缩合,氯甲酸酯酰胺化,设计合成得到8个新化合物1 a~1 h。对合成的目标化合物进行了初步的体外抗乙肝病毒药理活性实验。结果:设计合成的8个化合物对HBsAg和HBeAg都有一定的抑制作用,其中化合物1d的抑制活性优于拉米夫定。结论:5-取代嘧啶开环核苷膦酸酯类化合物保持抗病毒活性,N6位长链脂肪氯甲酸酯取代的化合物抗HBV病毒活性较好。Abstract: Objective :To study on synthesis and antiviral activities of 5-substituted pyrimidine acyclic nucleoside phosphonate compounds on HBV. Methods : Starting with substituted pyrimidine,we synthesized 8 firstly reported compounds 1a~1h.Preliminary pharmacological test was made on HBV. Results :TThe test results show the inhibitory rate of targeted compounds on HBsAg and HBeAg is normal,but 1d is higher than lamivudine. Conclusion :5-substituted pyrimidine acyclic nucleoside phosphonate compounds keep the normal activities on HBV and introduce long chain of chloroformate at N6 of pyrimidine shows better activity.
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Key words:
- 5-substituted pyrimidine /
- chemical synthesis /
- acyclic nucleotide /
- anti-HBV activity
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