新型醛糖还原酶抑制1-乙酰基-1H-吲哚-3-乙酸酯的合成及其抑制活性

Synthesis and Inhibitory Activity of Novel Aldose Inhibitor Reductase 1-Acetyl-1H-indole-3-acetate

醛糖还原酶抑制剂(ARIs)抑制多元醇途径的醛糖还原酶是治疗糖尿病并发症的重要策略。以2-氯苯甲酸为起始原料,在碱性条件下经铜催化,与甘氨酸反应生成氯代邻羧基苯基甘氨酸,再与乙酸酐反应,生成N-乙酰基邻羧基苯甲酸。然后在吡啶催化下合环,生成1-乙酰基-^(1)H-吲哚-3-乙酸酯(AIA),总收率为79.0%,纯度为99.0%。通过^(1)H NMR、^(13)C NMR和MS(ESI)对其结构进行表征,并对该化合物的的醛糖还原酶抑制活性进行测定,IC 50=9.4×10^(-2)μM。

Inhibition of polyol pathway Aldose reductase by Aldose reductase inhibitors(ARIs)is an important strategy for the treatment of diabetic complications.In this experiment,2-chlorobenzoic acid was used as the starting material,under alkaline conditions,reacted with glycine to generate chloro-o-carboxyphenylglycine,and then reacted with acetic anhydride to generate N-acetyl-o-carboxybenzoic acid,and then pyridine catalyzed under the cyclone to form 1-acetyl-^(1)H-indole-3-acetate(AIA).The total yield is 79.0%,and the purity is 99.0%.Its structure was characterized by^(1)H NMR,^(13)C NMR and MS(ESI),and the aldose reductase inhibitory activity of the compound was determined,and its IC 50 value was 9.4×10^(-2)μM.