Design and synthesis of potent and selective aldose reductase inhibitors based on pyridylthiadiazine scaffold

被引：30

作者：

Chen, Xin ^{[1
]}

Yang, Yanchun ^{[1
]}

Ma, Bing ^{[1
]}

Zhang, Shuzhen ^{[1
]}

He, Minlan ^{[1
]}

Gui, Dequan ^{[1
]}

Hussain, Saghir ^{[1
]}

Jing, Chaojun ^{[1
]}

Zhu, Changjin ^{[1
]}

Yu, Qun ^{[2
]}

Liu, Yan ^{[3
]}

机构：

[1] Beijing Inst Technol, Dept Appl Chem, Beijing 100081, Peoples R China

[2] Beijing Inst Transfus Med, Beijing 100850, Peoples R China

[3] Xiamen Univ, Coll Chem & Chem Engn, Xiamen 361005, Peoples R China

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2011年 / 46卷 / 05期

基金：

北京市自然科学基金;

关键词：

Pyrido[2,3e]-[1,2,4]-thiadiazine; Acetic acid derivative; Inhibitor; Aldose reductase; ACETIC-ACID DERIVATIVES; DIABETIC COMPLICATIONS; CARBOXYLIC-ACID; ACCUMULATION; SUBSTRATE; TYROSINE-48; CATALYSIS; ENZYME; NERVE; LENS;

D O I：

10.1016/j.ejmech.2011.01.072

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of pyrido[2,3-e]-[1,2,4]-thiadiazine 1,1-dioxide acetic acid derivatives were synthesized and tested for their inhibitory activity against aldose reductase (ALR2). These derivatives were found to be potent aldose reductase inhibitors with IC50 values ranging from 0.038 mu M to 11.29 mu M. Most but not all of them showed a strong ALR2 inhibition activity and significant selectivity, which were further supported by docking studies. Of these inhibitors, compound 7d exhibited highest inhibition activity. Structure activity relationship studies indicate the requirement of N2-benzyl group with electron-withdrawing substituents and N4-acetic acid group in the pyridothiadiazine scaffold. (C) 2011 Elsevier Masson SAS. All rights reserved.

引用

页码：1536 / 1544

页数：9

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