Organocatalyzed solvent free an efficient novel synthesis of 2,4,5-trisubstituted imidazoles for α-glucosidase inhibition to treat diabetes

A new and efficient solvent free synthesis of 2,4,5-trisubstituted imidazoles (3a-3j) was achieved by N-acetyl glycine (NAG) catalyzed three components condensation of aldehydes, benzil and ammonium acetate. Our synthetic methodology accommodated a range of various substituted alkyl and aryl aldehydes. Evaluation of alpha-glucosidase inhibitory activity of these imidazole derivatives revealed that most of them presented good alpha-glucosidase inhibition at low micro- molar concentrations. Among the synthesized compounds, compound 3c, bearing the ortho- hydroxy phenyl substituent at position 2 displayed the highest inhibitory activity with an IC50 value 74.32 +/- 0.59 mu M. In silico molecular docking for all compounds and computational studies of the most active compound 3c were also performed. (C) 2014 Elsevier Inc. All rights reserved.