目的 合成一系列帕拉米韋巰基二肽前藥并考察其在不同介質(zhì)中的穩(wěn)定性。方法 以帕拉米韋結(jié)構(gòu)中1位羧基為反應(yīng)位點(diǎn)，巰基二肽為載體，通過酯化反應(yīng)合成一系列帕拉米韋巰基二肽前藥。采用高效液相色譜法測定帕拉米韋巰基二肽前藥在不同pH值緩沖溶液、大鼠胃液、大鼠小腸液、人工胃液（含胃蛋白酶）、人工腸液（含胰酶）、大鼠血漿中的穩(wěn)定性，采用一級動力學(xué)方程計(jì)算降解速率常數(shù)。結(jié)果 合成了4個帕拉米韋巰基二肽前藥，它們在胃腸道中穩(wěn)定性良好。結(jié)論 帕拉米韋巰基二肽前藥具有良好的穩(wěn)定性，為帕拉米韋口服給藥的開發(fā)可提供依據(jù)。

Objective To synthesize a series of peramivir mercapto dipeptide prodrugs and investigate their stability at the different medium. Methods A series of prodrugs of peramivir were synthesized by esterification with 1 carboxyl group in the structure of peramivir as the reaction site and phobic dipeptide as the carrier. The stability of peramivir merapto dipeptide prodrug in different pH buffer solutions, rat gastric juice, rat small intestinal juice, artificial gastric juice (containing pepsin), artificial intestinal juice (containing pancreatin), and rat plasma were determined by HPLC method. First-order kinetic equations were used to calculate the degradation rate constant. Results Four peramivir mercapto dipeptide prodrugs were synthesized with good stability at the different medium. Conclusion Peramivir mercapto dipeptide prodrugs have good stability, which can provide a basis for the development of peramivir oral administration.

R914

國家自然科學(xué)基金資助項(xiàng)目（81860630；81360485）；江西省研究生創(chuàng)新專項(xiàng)資金項(xiàng)目（YC2019-S363）