Preparation of new derivatives of 4-dihydro-2H-spiro[benzo[f]pyrido[1,2-b][1,2,4]triazepines.

In the present study, a convenient synthetic approach to a novel series of spirocyclic compounds was developed. The key intermediates, 1,6-diamino-2-oxo-1,2-dihydropyridine-3,5-dicarbonitriles, are readily accessible from the reaction of cyanoacetohydrazide with various arylidenemalononitriles. Condensation of these intermediates with dimedone affords 6-amino-1-((5,5-dimethyl-3-oxocyclohex-1-en-1-yl)amino)-4-(aryl)-2-oxo-1,2-dihydropyridine-3,5-dicarbonitrile derivatives. Subsequent reaction with indenoquinoxaline or ninhydrin initiates spirocyclization, leading to the formation of previously undescribed heterocycles. The progress of all reactions was monitored by thin-layer chromatography (TLC) using ethyl acetate/hexane mixtures in a 6:1 ratio and a methanol/toluene mixture in a 9:1 ratio as eluents. UV light and an iodine chamber were used for visualization. All synthesized compounds were fully characterized by IR spectroscopy, ¹H NMR spectroscopy, and ¹³C NMR spectroscopy. To evaluate their potential as drug candidates, an in silico predictive study was carried out. ADMET parameters were also calculated to assess drug-likeness. Molecular docking against a panel of cancer-related protein targets revealed high binding affinities, suggesting that these compounds possess significant anticancer activity. Furthermore, the antidotal (protective) activity of the synthesized derivatives against the herbicide 2,4-D was investigated experimentally on sunflower cultivar Master. Growth-regulating activity on sunflower cultivar Master was also studied. Overall, these new spiro compounds represent attractive scaffolds for further development as anticancer agents.