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

• A novel method has been developed for the facile and efficient synthesis of imidazole derivatives.
• This simple and versatile protocol yielded the targeted compounds in good to excellent yields.
• Most of the synthesized compounds have exhibited potent α-glucosidase activity.
• Generally ortho-hydroxy phenyl substituted compounds showed more promising inhibition.
• Compound 3c presented the highest inhibitory activity with IC50 value 74.32 ± 0.59 μM.

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 α-glucosidase inhibitory activity of these imidazole derivatives revealed that most of them presented good α-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 μM. In silico molecular docking for all compounds and computational studies of the most active compound 3c were also performed.

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