Ionic liquid-promoted multicomponent synthesis of fused tetrazolo[1,5-a]pyrimidines as α-glucosidase inhibitors

A simple and facile synthesis of fused tetrazolo[1,5-a]pyrimidine derivatives based on the multicomponent reaction of acetophenone, dimethylformamidedimethylacetal and 5-aminotetrazole is described. A green chemical synthesis has been achieved by using1-butyl-3-methylimidazolium hydrogen sulfate [Bmim]HSO4 ionic liquid as a reusable medium. Short synthetic route, operational simplicity, good yields, eco-friendliness and recyclability of the ionic liquid are the advantages of this method. The synthesized compounds were screened for α-glucosidase inhibitory activity using yeast maltase (MAL12) as a model enzyme. Inhibition and kinetic studies have shown that compounds 4d and 4g are found to be active showing comparable inhibitory potency with acarbose. Further docking studies of the derivatives with MAL12 homology model identified a similar binding mode consistent with the binding of acarbose. These studies along with in silico predicted ADMET properties suggest that these molecules could represent a new scaffold that may be useful for the development of new anti-diabetic drugs.

Figure optionsDownload as PowerPoint slide