Efficient Synthesis of Pyrazolopyrimidines Containing a Chromane Backbone with Biological Activity Evaluation

In this study, a novel series of chromeno[4′,3′:3,4]pyrazolo[1,5-a]pyrimidine derivatives was efficiently synthesized through a multistep protocol using substituted aminochromenopyrazoles and activated methylene compounds. The synthetic methodology was robust and yielded structurally well-characterized products, as confirmed by NMR, IR, MS, and elemental analysis. The antimicrobial activities of the synthesized compounds were systematically evaluated against a panel of Gram-positive and Gram-negative bacterial strains. Several derivatives demonstrated significant antibacterial potential, with compound 6a exhibiting superior activity comparable to or exceeding that of standard Ampicillin. A preliminary structure-activity relationship (SAR) analysis revealed that specific substituents, such as hydroxyl, amino, and nitrile groups, play a critical role in enhancing antimicrobial efficacy. Furthermore, plausible mechanisms of action─such as DNA gyrase inhibition, membrane disruption, and potential dihydrofolate reductase interaction─were proposed based on structural features and recent literature. These findings suggest that the synthesized chromeno-pyrazolopyrimidines represent promising scaffolds for the development of new antibacterial agents targeting resistant pathogens.