Identification of 9H-purin-6-amine derivatives as novel aldose reductase inhibitors for the treatment of diabetic complications

被引：4

作者：

Zhu, Junkai ^{[1
]}

Qi, Gang ^{[1
]}

Kuang, Yan ^{[1
]}

Zhao, Yating ^{[1
]}

Sun, Xinjie ^{[1
]}

Zhu, Changjin ^{[2
]}

Hao, Xin ^{[1
]}

Han, Zhongfei ^{[1
,2
]}

机构：

[1] Yancheng Inst Technol, Fac Chem & Chem Engn, Yancheng, Peoples R China

[2] Beijing Inst Technol, Dept Appl Chem, Beijing, Peoples R China

来源：

ARCHIV DER PHARMAZIE | 2022年 / 355卷 / 08期

基金：

中国国家自然科学基金;

关键词：

9H-purin-6-amine; aldose reductase inhibitors; diabetic complications; POTENT;

D O I：

10.1002/ardp.202200043

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of 9H-purin-6-amine derivatives as aldose reductase (ALR) inhibitors were designed and synthesized. Most of these derivatives, having a C6-substituted benzylamine side chain and N9 carboxylic acid on the core structure, were found to be potent and selective ALR inhibitors, with submicromolar IC50 values against ALR2. Particularly, compound 4e was the most active with an IC50 value of 0.038 mu M, and it was also proved to be endowed with excellent inhibitory selectivity. The structure-activity relationship and molecular docking studies highlighted the importance of the carboxylic acid head group along with different halogen substituents on the C6 benzylamine side chain of the 9H-purin-6-amine scaffold for the construction of strong and selective ALR inhibitors.

引用

页数：9

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