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

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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.

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Acknowledgements

This work was financially supported by grants from Tehran University of Medical Sciences with Project No. 98-03-33-43696.

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Authors and Affiliations

  1. Medicinal Plants Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

    Mina Saeedi

  2. Persian Medicine and Pharmacy Research Center, Tehran University of Medical Sciences, Tehran, Iran

    Mina Saeedi & Tahmineh Akbarzadeh

  3. Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

    Maryam Raeisi-Nafchi, Sepideh Sobhani & Tahmineh Akbarzadeh

  4. Department of Medicinal Chemistry, School of Pharmacy-International Campus, Iran University of Medical Sciences, Tehran, Iran

    Seyedeh Sara Mirfazli

  5. Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, P.O. Box 14155-6451, Tehran, 1417614411, Iran

    Mahsa Zardkanlou, Somayeh Mojtabavi & Mohammad Ali Faramarzi

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  1. Mina Saeedi
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Correspondence to Tahmineh Akbarzadeh.

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This paper is dedicated to the memory of our unique teacher in Chemistry and Medicinal Chemistry, Professor Abbas Shafiee (1937–2016).

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Saeedi, M., Raeisi-Nafchi, M., Sobhani, S. et al. Synthesis of 4-alkylaminoimidazo[1,2-a]pyridines linked to carbamate moiety as potent α-glucosidase inhibitors. Mol Divers 25, 2399–2409 (2021). https://doi.org/10.1007/s11030-020-10137-8

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