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

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.

Keywords: 4-Alkylaminoimidazo[1,2-a]pyridine; Carbamates; Synthesis; α-Glucosidase.