基于喹喔啉酮结构的醛糖还原酶抑制剂的设计合成与构效关系研究

A series of aldose reductase(ALR2) inhibitor candidates were designed and synthesized based on quinoxalin-2(1H)-one, and a carboxyl group was introduced at N1 position. Moreover, the side chain at C3 position was modified. All compounds were tested for ALR2 inhibitory activity, showing significant inhibition. The results also show that, among them, 2-(3-(4-hydroxyphenylpropenyl)-2-oxoquinoxaline-1(2H) -alkyl) acetic acid(4d) demonstrate the most potent inhibitory activity with an IC₅₀ value of 93 nmol/L, being equal to epalrestat(IC₅₀=83 nmol/L), which is the only commercial aldose reductase inhibitor(ARI). In addition, molecular docking experiments reveal that compound 4d can bind tightly to the active site of aldose reductase.