摘要
目的:合成吡硫醇前体药物,并研究其在不同pH缓冲溶液中及血浆中的水解动力学。方法:以吡硫醇和丙酸酐为原料,经过简单的酯化反应合成吡硫醇丙酯,利用RP-HPLC法测定前体药物的油水分配系数、溶解度、在不同pH值缓冲溶液中及血浆中的降解动力学。结果:经UV,IR,MS和NMR确证目标化合物的结构。前体药物的水解曲线呈V-型分布,pH值在5-6最稳定,血浆中前药可迅速转化成吡硫醇。结论:吡硫醇丙酯是具有良好前景的前体药物。
Objective:To synthesize pyritinol tetrapropionate ester prodrug, determine its aqueous stability at various pH values and bioreversion kinetics in rat plasma. Methods:Pyritinol tetrapropionate ester prodrug was synthesized by esterification reaction using pyritinol and propionic anhydride as the starting materials. Prodrug hydrolysis was studied in aqueous buffer solutions with pH 2 - 10 as well as 80% rat plasma solution by the reversed-phase high performance liquid chromatography (RP-HPLC) method, meanwhile the solubility and the partition coefficient of the prodrug were investigated. Results: The structure of systhesized prodrug was confirmed by IR, UV, MS and ^1H-NMR spectroscopy and it's purity was deteced by RP-HPLC. The prodrug exhibited a typical V-shape of a carboxylic ester with maximum stability at slight acidic pH 5.0 - 6.0. It could be hydrolyzed fastly by enzymes in 80% rat plasma. Conclusion: Pyritinol tetrapropionate ester prodrug is a promising prodrug.
出处
《中国新药杂志》
CAS
CSCD
北大核心
2007年第18期1488-1491,共4页
Chinese Journal of New Drugs
关键词
吡硫醇
前体药物合成
水解速率常数
血浆水解
pyritinol
prodrug synthesis
hydrolysis rate constants
blood degradation