Design and Synthesis of Novel Tetrazole–Imidazole Hybrids as Antidiabetic Agents by the Ugi-Azide Multicomponent Reaction

Diabetes remains a major worldwide health issue, requiring the development of new therapeutic agents. This study involved the design and synthesis of a series of tetrazole–imidazole hybrids as prospective antidiabetic agents utilizing the Ugi-azide multicomponent reaction. Ten novel compounds 4a–4j was successfully synthesized and characterized using various spectroscopic techniques. The in vitro antidiabetic efficacy of these compounds was assessed via α-glucosidase inhibition assay, demonstrating considerable inhibitory activity. Notably, compound 4j bearing a 2,4-bis(trifluoromethyl)phenyl moiety exhibited the highest potency with an IC50 of 3.58 μM, outperforming the standard inhibitor acarbose (IC50 = 650.10 μM). The structure–activity relationship analysis indicated that electron-withdrawing substituents, particularly fluorine and trifluoromethyl groups, enhance inhibitory potency. These findings emphasize the potential of tetrazole–imidazole hybrids as promising options for future development in antidiabetic medication research.