基于降低肾毒性的阿德福韦膦酸酯衍生物的设计与合成
Design and synthesis of phosphonates derivatives of Adefovir with reduced nephrotoxicity
作者：裴健颖;刘影;傅晓钟;欧瑜;李靖;董永喜;王永林;兰燕宇;
Author：
收稿日期： 年卷（期）页码：2012,27(05):-478-482
期刊名称：华西药学杂志
Journal Name：WEST CHINA JOURNAL OF PHARMACEUTICAL SCIENCES
关键字：阿德福韦;乙肝病毒;前药;非甾体药物
Key words：
基金项目：国家自然科学基金资助项目(批准号:20962004);;
贵州省社会发展攻关计划(No.QKHSYZ-2009-3081);;
贵州省高层次人才科研特助基金(批准号:TZJF-2009-36)
中文摘要
目的合成具有较高抗HBV活性与较低肾细胞毒性的新型阿德福韦衍生物。方法低温下,硫代N-Boc-L-氨基酸与1,2-二溴乙烷在NaH条件下制备硫代N-Boc-L-氨基酸-3-溴-1-丙基酯;非甾体抗炎药(布洛芬、酮洛芬、氟比洛芬)与3-溴-1-丙醇在DCC/DMAP条件下转变为非甾体抗炎药-3-溴-1-丙基酯;以上两种原料与阿德福韦在缩合剂N,N'-二环己基-4-吗啉基-咪(DCMC)存在下通过"一锅法"制备目标化合物。结果合成了6个未见文献报道的阿德福韦单硫代L-氨基酸酯,单非甾体抗炎药羧酸酯前药5a～5f。结论目标化合物及重要中间体结构均经过1HNMR、ESI-MS以及HRMS确证。
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