Synthesis of 4-alkylaminoimidazo[1,2- a ]pyridines linked to carbamate moiety as potent α -glucosidase inhibitors,Molecular Diversity

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Synthesis of 4-alkylaminoimidazo[1,2- a ]pyridines linked to carbamate moiety as potent α -glucosidase inhibitors
Molecular Diversity ( IF 3.9 ) Pub Date : 2020-10-12 , DOI: 10.1007/s11030-020-10137-8
Mina Saeedi _{1,

2} , Maryam Raeisi-Nafchi ₃ , Sepideh Sobhani ₃ , Seyedeh Sara Mirfazli ₄ , Mahsa Zardkanlou ₅ , Somayeh Mojtabavi ₅ , Mohammad Ali Faramarzi ₅ , Tahmineh Akbarzadeh _{2,

3}

Affiliation

Abstract

In this work, various imidazo[1,2-a]pyridines linked to carbamate moiety were designed, synthesized, and evaluated for their α-glucosidase inhibitory activity. Among synthesized compounds, 4-(3-(tert-Butylamino)imidazo[1,2-a]pyridin-2-yl)phenyl p-tolylcarbamate (6d) was the most potent compound (IC₅₀ = 75.6 µM) compared with acarbose as the reference drug (IC₅₀ = 750.0 µM). Kinetic study of compound 6d indicated a competitive inhibition. Also, the molecular docking study suggested desired interactions with the active site residues. In particular, hydrogen bonds and electrostatic interactions constructed by compound 6d afforded well-oriented conformation in the 3A4A active site.

Graphic abstract

中文翻译：

合成与氨基甲酸酯部分连接的 4-烷基氨基咪唑并[1,2-a]吡啶作为有效的 α-葡萄糖苷酶抑制剂

抽象的

在这项工作中，设计、合成了各种与氨基甲酸酯部分连接的咪唑并[1,2- a ]吡啶，并评估了它们的α-葡萄糖苷酶抑制活性。在合成的化合物中，与阿卡波糖相比，4-(3-(叔丁基氨基)咪唑并[1,2- a ]吡啶-2-基)苯基对甲苯基氨基甲酸酯 ( 6d ) 是最有效的化合物 (IC ₅₀ = 75.6 µM)作为参考药物（IC ₅₀ = 750.0 µM）。化合物6d的动力学研究表明存在竞争性抑制。此外，分子对接研究表明与活性位点残基存在所需的相互作用。特别是，化合物6d构建的氢键和静电相互作用在 3A4A 活性位点中提供了良好定向的构象。

图文摘要

更新日期：2020-10-12

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