新型磺酰类醛糖还原酶抑制剂的合成及活性研究

Synthesis and Inhibitory Activity of Sulfonyl Compounds as New Aldose Reductase Inhibitors

以2,4-二甲苯胺为原料,设计并合成了一系列环外磺酰胺(酯)类衍生物,对目标化合物的醛糖还原酶(ALR2)抑制活性进行了测定,并利用分子对接方法研究了抑制剂与醛糖还原酶蛋白的结合模式.结果显示环外磺酰类化合物8a-d,12a-b,16a-b具有良好的体外醛糖还原酶抑制活性,分子模拟预测其能与酶蛋白的活性位点空腔较好结合.化合物8a-d是一类新型醛糖还原酶抑制剂,活性良好,并可作为先导化合物探索活性更高的醛糖还原酶抑制剂.

A series of sulfonamide （ester） derivatives were designed and synthesized by using 2,4- dimethylaniline as the starting material. The in vitro inhibitory activities of the target compounds against aldose reductase were evaluated. Docking studies were performed to examine the manner by which newly prepared compounds interact with ALR2. It was found that sulfonyl compounds 8a-d, 12a-b, 16a-b show moderate inhibitory activities against aldose reductase and they interact with the ALR2 active site pocket in a good way. Compounds 8a-d are found as a new type of aldose reductase inhibitors with moderate activity and they can be used as lead compounds to explore ARIs with higher activity.