布洛芬丁香酚酯前体药物的合成及其水解动力学

目的合成布洛芬丁香酚酯并研究其在不同pH水溶液中及血浆、肝匀浆中的水解动力学。方法以布洛芬和丁香酚为原料,经过酯化反应合成了布洛芬前体药物布洛芬丁香酚酯,利用HPLC法测定不同pH值的缓冲溶液、血浆及肝均浆中药物水解动力学。经UV、IR、MS和NMR确证了目标化合物的结构。结果布洛芬丁香酚酯在pH为1.10~9.96时水解速率常数不受pH影响,pH为10.91~11.91时随pH值增加水解速率增大;在血浆及肝均浆中布洛芬丁香酚酯可迅速水解成布洛芬和丁香酚。结论布洛芬丁香酚酯是一个具有良好前景的非甾体抗炎前体药物。

Synthesis of ibuprofen eugenol ester prodrug and its hydrolysis kinetics

Objective To synthesize ibuprofen eugenol ester and study its hydrolysis kinetics.Methods Ibuprofen eugenol ester was synthesized by acylation reaction using ibuprofen and eugenol as the starting materials.The kinetics of ester hydrolysis was studied in aqueous buffer solutions pH 1.10-10.91 as well as rat plasma and rat liver homogenate by the HPLC method.Results The structure of ibuprofen eugenol ester was confirmed by IR,UV,MS and(()~1H)NMR spectroscopy and its purity was established by HPLC.The ester was stable at a wide pH range form 1.10 to 9.96.However,it was hydrolyzed by enzymes from 80% rat plasma and rat liver homogenate to form ibuprofen and eugenol.Conclusions Ibuprofen eugenol ester is a promise prodrug of non-steroidal anti-inflammatory drugs(NSAIDs).