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

• DOI: 10.1007/s11030-020-10137-8
• Publication Date: 2020-10-12T16:03:58Z
• Authors: Mina Saeedi; Maryam Raeisi-Nafchi; Sepideh Sobhani; Seyedeh Sara Mirf...; Mahsa Zardkanlou; Somayeh Mojtabavi; Mohammad Ali Fara...; Tahmineh Akbarzadeh
• Keywords: Moiety; Acarbose; Carbamate; Docking (animal); Lead compound; IC50; Active compound

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.