Aminomethylation of 1,6-diamino-4-aryl-2-oxo-1,2-dihydropyridine-3,5-dicarbonitriles under the action of excess of formaldehyde in ethanol has led to the formation of 7-aryl-3-(hydroxymethyl)-5-oxo-1,2,3,5-tetrahydro[1,2,4]triazolo[1,5-a]pyridine-6,8-dicarbonitriles. Bioavailability parameters of the obtained compounds have been predicted in silico and the possible protein targets have been predicted via the protein-ligand docking.

The reaction of 1,6-diamino-2-oxo-1,2-dihydropyridine-3,5-dicarbonitriles, which are easily available through the reaction of cyanoacetohydrazide with arylmethylene malononitriles, with ninhydrin leads to the formation of novel dihydroindeno[1,2-e]pyrido[1,2-b][1,2,4]triazines. Another active carbonyl compound, glyoxal, reacts with 1,6-diamino-2-oxo-1,2-dihydropyridine-3,5-dicarbonitriles under mild conditions to give functionalized 6-oxo-6H-pyrido[1,2-b][1,2,4]triazine-7,9-dicarbonitriles.

Here, 1,6-diamino-2-oxo-1,2-dihydropyridine-3,5-dicarbonitriles, prepared by the reaction of cyanoacethydrazide with arylmethylene malononitriles, react with 1-cyanoacetyl-3,5-dimethylpyrazole and chloroacetyl chloride to give corresponding cyanoacetamides and chloroacetamides. The reaction with phthalic anhydride proceeds under harsh conditions to give 4,7-dioxo-4,7-dihydropyrido[1′,2′:2,3][1,2,4]triazolo[5,1-a]isoindole- 1,3-dicarbonitriles.

Accumulation of beta-amyloid peptide (Aß) in the brain followed by the formation of fibrils is a key factor in the progression of Alzheimer's disease (AD). One therapeutic strategy for AD consists in inhibition of fibrillation in its early stages. Today, a large body of research data has been accumulated indicating the ability of nitrogen-containing heterocycles with various substituents to directly bind to Aβ and inhibit its oligomerization. In this work, we consider a new representative of this class of substances – a pyrido-1,3,5-triazine derivative (AAD82) – and construct models of ADD82 complexes with monomeric and protofibrillar forms of Aβ. The correlation of the set of amino acid residues involved in the formation of such a complex, as well as the total energy of its formation, are analyzed.