Virchow Canonica1, Zafiriou Bogdanos2, Davis Rhoads3, Fenaroli Belmont2,3*

ABSTRACT

A novel series of fused nicotinonitrile derivatives was successfully constructed through the reaction of 2,6-dioxonicotinonitrile (compound 1) with a variety of electrophilic reagents. Specifically, the reaction of pyridone 1 with different benzylidene derivatives (2, 3, and 7) led to the formation of pyrano[2,3-b]pyridine derivatives 4 and 11, respectively. Further, pyridone 1 underwent reactions with ?,?-unsaturated carbonyl compounds and benzoyl isothiocyanate, yielding the corresponding pyridine derivatives 11–13 and 16. In addition, sulfurization and selenation of pyridone 1 in the presence of triethylamine afforded the fused heterocycles 14 and 15. The structures of all newly synthesized compounds were confirmed using IR, NMR spectroscopy, and elemental analysis. A selection of these pyridine derivatives was evaluated for anticancer activity, revealing promising cytotoxic potential. These findings suggest that the newly engineered fused nicotinonitrile scaffolds may serve as valuable leads for the development of novel anticancer agents. Keywords: Fused nicotinonitrile; Pyrano[2,3-b]pyridine; Heterocyclic synthesis; Dihydropyridine; Anticancer evaluation.