Imidazol-1,2,3-triazole Derivatives as Novel and Potent Scaffolds of α-Glucosidase Inhibitors: Synthesis and Biological Evaluations

A treatment for type 2 diabetes mellitus (T2DM) that has been approved is the inhibition of α-glucosidase. Using a simple and straightforward three-step synthetic route that utilized a Cu(I)-catalyzed azide–alkyne cycloaddition (CuAAC) click chemistry approach in the last step, a new series of substituted 1H-imidazol-1H-1,2,3-triazoles, specifically 5a–5j, were synthesized in an effort to create new anti-α-glucosidase agents. 1H and 13C NMR spectroscopy and mass spectrometry were used to characterize these motifs in great detail. The positive control in this investigation was acarbose, which had an IC50 value of 750.0 µM. The 1H-imidazol-1H-1,2,3-triazoles that were replaced showed inhibitory potencies several times stronger than those of conventional medicines, with IC50 values ranging from 14.89 to 311.20 μM. In particular, compounds containing fluorine groups as aryl substitutions exhibited anti-α-glucosidase activity with an IC50 value of 14.89 μM (5f = 4-CF3), which was 53 times stronger than the positive control acarbose, while compounds carrying the 2,4-(F)2 motif had an IC50 value of 29.50 μM, which was 25 times stronger.