Development of an Efficient Niobium-Catalyzed Hantzsch Multicomponent Reaction Methodology

Diabetes mellitus is a major metabolic disorder, and inhibition of dipeptidyl peptidase-4 (DPP-IV) represents an effective strategy for glycemic control.¹ Previous HQSAR and molecular docking studies enabled the identification of key structural features related to biological activity, supporting the design of new DPP-IV ligands. 1,4-Dihydropyridines (1,4-DHPs) are privileged scaffolds in medicinal chemistry and can be synthesized through the Hantzsch multicomponent reaction. In this work, a niobium-catalyzed methodology for the synthesis of symmetrical 1,4-DHPs was developed by evaluating different reaction conditions and catalysts. Reactions were performed under reflux (Method A) and microwave irradiation (Method B) using niobium pentoxide (NBO), niobium phosphate (NBP), and ammonium niobium oxalate (ANO) as catalysts. Product yields ranged from 13–65% under reflux and 44–87% under microwave irradiation. NBO and NBP showed the best catalytic performance, while microwave-assisted reactions afforded higher yields, shorter reaction times, and an efficient protocol for preparing symmetrical 1,4-dihydropyridines.