磷酸酯前药在药物研究中的应用  

Application of phosphates and phosphonates prodrugs in drug research and development

作　　者：姬勋[1,2] 王江[1] 张磊[1] 赵临襄[2] 蒋华良[1,2] 柳红[1] 

机构地区：[1]中国科学院上海药物研究所,新药研究国家重点实验室,上海201203 [2]沈阳药科大学制药工程学院,辽宁沈阳110016

出　　处：《药学学报》2013年第5期621-634,共14页Acta Pharmaceutica Sinica

基　　金：国家杰出青年科学基金资助项目(81025017)

摘　　要：根据药物分子的结构特点,磷酸酯前药可分为两类:一类是分子中含有磷酸基团的药物。该类药物由于脂溶性差而引入一些保护性片段,降低磷酸基团的亲水性,提高脂溶性和透膜能力,从而提高药物的生物利用度;另一类是为了改善药物的水溶性而引入磷酸基团的药物,该类药物利用磷酸基团极性大的特点降低药物的脂溶性,调节药物的理化性质,提高成药性。本文以结构修饰和优化出发,从药物的理化性质(脂溶性和水溶性)、药物安全性和药物代谢动力学性质三个方面介绍磷酸酯前药在药物研究中的应用。Based on the character of the molecular structure, the prodrugs of phosphates and phosphonates were divided into two categories. The first is the drug which contained the phosphate group, introducing protected groups to increase lipophilicity and improve bioavailability. The other one is the drug which had no phosphate group, introducing the phosphate group into molecules to enhance the solubility, regulate the distribution coefficient and enhance the drug-like property. This review focuses on the application of phosphates and phosphonates in drug research and development based on improvement of physico-chemical property, drug safety and the pharmacokinetics.

关 键 词：磷酸酯前药 生物利用度 脂溶性 水溶性 稳定性 HepDirect前药 

分 类 号：R916[医药卫生—药学]