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

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Identification of 9H-purin-6-amine derivatives as novel aldose reductase inhibitors for the treatment of diabetic complications
Archiv der Pharmazie ( IF 4.3 ) Pub Date : 2022-04-24 , DOI: 10.1002/ardp.202200043
Junkai Zhu ₁ , Gang Qi ₁ , Yan Kuang ₁ , Yating Zhao ₁ , Xinjie Sun ₁ , Changjin Zhu ₂ , Xin Hao ₁ , Zhongfei Han _{1,

2}

Affiliation

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 μM, 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.

中文翻译：

鉴定 9H-purin-6-amine 衍生物作为治疗糖尿病并发症的新型醛糖还原酶抑制剂

设计合成了一系列 9 H -purin-6-amine 衍生物作为醛糖还原酶 (ALR) 抑制剂。大多数这些衍生物，在核心结构上具有 C6 取代的苄胺侧链和 N9 羧酸，被发现是有效和选择性的 ALR 抑制剂，对 ALR2具有亚微摩尔的 IC _50值。特别是化合物4e的活性最强，IC ₅₀值为0.038 μM，同时也被证明具有优异的抑制选择性。构效关系和分子对接研究强调了羧酸头基以及 9 H的 C6 苄胺侧链上不同卤素取代基的重要性-purin-6-amine 支架，用于构建强效和选择性 ALR 抑制剂。

更新日期：2022-04-24

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