ProTide-上海有机化学研究所.PDF

DOI: 10.6026/cjoc201705022 综述与进展 有机化学 Chinese Journal of Organic Chemistry REVIEW 磷酰胺酯前药策略及ProTide 技术在药物研发中的应用与进展 a a a a, b a, b a, b* 聂飚 金传飞 钟文和 任青云 张英俊 张霁 a b （广东东阳光集团药业研究院 东莞 抗感染新药研发国家重点实验室 523871 ） 摘要 本文介绍了磷酰胺酯前药策略和ProTide 技术在抗病毒和癌症药物研究领域的发展历史和进展，对核苷磷酰胺酯 前药的合成, 立体选择性构建手性核苷磷酰胺酯前药合成方法的最新突破以及其在新药研究中的应用做了述评，指出该 技术对新药设计与结构修饰改造，包括挖掘老药新用等方面值得学习借鉴和推广. 关键词 磷酰胺酯; 前药；核苷；抗病毒药物；磷酸盐和磷酸酯; ProTide Application and Recent Progress of Phosphoramidate Prodrugs Strate- gies and ProTide Technology in Drug Discovery * Nie, Biao Jin, Chuanfei Zhong, Wenhe Ren, Qingyun Zhang, Yingjun Zhang, Ji (HEC Pharm Group, HEC RD Center, the State Key Laboratory of Anti-Infective Drug Development, Guangdong, Dongguan 523871) Abstract This review provides the brief history for the development and advances of ProTide strategies in the field of anti- viral and anticancer pharmaceutical development. A summary is provided for the synthesis of nucleoside phosphoramidates, recent breakthroughs in the stereoselective assembly of chiral prodrugs and its application. This technology is extremely useful and has simplified innovative drug design of phosphorous-containing prodrugs. Simplifying such structural modification may create a new avenue of competition in the invention of new medicines from the parent drug. Keywords phosphoramidates ；prodrugs; nucleosi