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

作　　者：李卓玲 杨威龙 赵珊 王淑红 李臣 王志兵[1] 修志明 LI Zhuoling;YANG Weilong;ZHAO Shan;WANG Shuhong;LI Chen;WANG Zhibing;XIU Zhiming(College of Chemistry and Life Sciences,Changchun University of Technology,Changchun 130012,China;Jilin Collaborative Innovation Center for Antibody Engineering,Jilin Medical College,Jilin 132013,China;Changchun BC&HC Pharmaceutical Technology Co.,Ltd.,Changchun 130012,China)

机构地区：[1]长春工业大学化学与生命科学学院,吉林长春130012 [2]吉林医药学院吉林省抗体工程科技协同创新中心,吉林吉林132013 [3]长春百纯和成医药科技有限公司,吉林长春130012

出　　处：《合成化学》2024年第2期124-127,共4页Chinese Journal of Synthetic Chemistry

基　　金：吉林省创新创业人才项目(2020038);吉林省科技厅项目(20210510008RQ)。

摘　　要：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.

关 键 词：糖尿病并发症 醛糖还原酶抑制剂 合成 抑制活性 1-乙酰基-1 H-吲哚-3-乙酸酯 

分 类 号：Q5[生物学—生物化学]