阿奇霉素新衍生物的设计、合成及抗病毒活性  

DESIGN, SYNTHESIS AND ANTIVIRAL ACTIVITY OF SOME NEW AZITHROMYCIN DERIVATIVES

作　　者：谢麟[1] 沈家祥 雷小平[1] 

机构地区：[1]北京大学药学院,北京100083 [2]北京集才医药技术开发有限公司,北京100083

出　　处：《药学学报》2002年第12期942-945,共4页Acta Pharmaceutica Sinica

基　　金：中国西尔研究开发基金资助 ( 1999 0 9)

摘　　要：目的　利用阿奇霉素的体内分布特点 ,设计了新的阿奇霉素衍生物 ,寻找具抗病毒活性的新化合物。方法　利用O2 计算机辅助药物设计工作站 ,设计并合成新阿奇霉素衍生物 ,用抗乙肝病毒药物筛选模型进行了药理活性研究。结果　设计合成了 3个新的阿奇霉素衍生物和两个新中间体 ,目的物 4a ,4b ,5经波谱分析结构准确。药理活性结果表明化合物具抗病毒活性。结论　化合物 4b具很好的抗病毒活性。证实化合物设计思路正确 ,可以指导类似化合物的设计。AIM To design and synthesize new derivatives of azithromycin, based on the distribution features of azithromycin in vivo and to improve the selectivity and activity of antiviral agents using the 15 membered-ring macrolide as the carrier. METHODS New derivatives of azithromycin were designed on O 2 computer-aided workstation and synthesized through two paths, anti-HBV (hepatits B viral) reagent screening model was used to carry out pharmacological research. RESULTS Three new azithromycin derivatives and two intermediates were synthesized. Target compounds 4a, 4b and 5 are confirmed to be correct by spectrum analysis. Pharmacological results indicate that some of them showed antiviral activity. CONCLUSION One of the new azithromycin derivatives 4b showed anti-virus effect. The design method is correct, which may be used to instruct the design of similar compounds.

关 键 词：阿奇霉素 阿奇霉素衍生物 抗病毒活性 计算机辅助药物设计 药物合成 

分 类 号：R914.2[医药卫生—药物化学] R914.[医药卫生—药学]