Enaminones have garnered significant attention because of their unique properties and their importance in synthetic chemistry as highly versatile building blocks. In this study, a novel series of heterocyclic compounds based on pyridine and pyrimidine scaffolds was synthesized through the reactions of enaminones 2 with nitriles and various ammonia derivatives. The structures of the newly synthesized compounds were confirmed using multiple spectroscopic techniques, including IR, ¹H-NMR, ¹³C-NMR, and MS, as well as elemental analysis. Evaluation of the antimicrobial activity of these heterocycles demonstrated notable potency, particularly among the pyrimidine analogues.