Design, Synthesis and Biological Evaluation of Imidazo[1,2-a]pyridine Derivatives as Novel DPP-4 Inhibitors

Chemical Biology & Drug Design
Qing LiHuibin Zhang

Abstract

A new series of DPP-4 inhibitors with imidazo[1,2-a]pyridine scaffold were designed by exploiting scaffold hopping strategy and docking study. Based on docking binding model, structural modifications of 2-benzene ring and pyridine moieties of compound 5a led to the identification of compound 5d with 2, 4-dichlorophenyl group at the 2-position as a potent (IC50  = 0.13 μm), selective (DPP-8/DPP-4 = 215 and DPP-9/DPP-4 = 192) and in vivo efficacious DPP-4 inhibitor. Further, molecular docking revealed that compound 5d could retain key binding features of DPP-4 with the pyridine moiety of imidazo[1,2-a]pyridine ring providing an additional π-π interaction with Phe357 of DPP-4. Compound 5d might be a promising lead for further development of novel DPP-4 inhibitor treating T2DM.

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Citations

Jun 8, 2018·Archiv der Pharmazie·Ankit RohillaMohammad Shahar Yar
Nov 28, 2017·Future Medicinal Chemistry·María José Ojeda-MontesCristina Valls
Apr 24, 2020·Bioorganic Chemistry·Xinxian DengFaqin Jiang
Jun 10, 2021·The Journal of Pharmacy and Pharmacology·Samvel N SirakanyanPřemysl Mladěnka
Aug 25, 2021·Bioorganic & Medicinal Chemistry·Shubham KumarAmit Mittal
Nov 16, 2021·Journal of Biomolecular Structure & Dynamics·Samima KhatunFirdoos Ahmad Sofi

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