7-(2-Aryl-1-cyanovinyl)-1,2,3,4-tetrahydropyrazolo[1,5-a][1,3,5]triazine-8-carbonitriles: Synthesis and Biological Activity

Abstract

A new method was proposed for the preparation of 5-amino-3-(cyanomethyl)-1H-pyrazole-4-carbonitrile by reaction of the potassium salt of malononitrile dimer with hydrazinium sulfate. The reaction of 5-amino-3(cyanomethyl)-1H-pyrazole-4-carbonitrile with aromatic aldehydes in the presence of catalytic amounts of morpholine leads to the formation of Knoevenagel condensation products. Aminomethylation of the resulting (Z)-5-amino-3-(2-aryl-1-cyanovinyl)-1H-pyrazole-4-carbonitriles with primary aromatic amines and excess aqueous HCHO in refluxing DMF leads to the formation of 7-(2-aryl-1-cyanovinyl)-1,2,3,4-tetrahydropyrazolo[1,5-a][1,3,5]triazine-8-carbonitriles. Bioavailability parameters were studied in silico, and possible protein targets were predicted by protein-ligand docking. In an in vitro experiment on cultures of E. coli, S. aureus and B. pumilis, 5-amino-3-(cyanomethyl)-1H-pyrazole-4-carbonitrile does not show any noticeable antibacterial effect. At the same time, three compounds of the pyrazolo[1,5-a][1,3,5]triazine series showed a pronounced antidote effect against the herbicide 2,4-D on sunflower seedlings in a laboratory experiment, for one compound a noticeable growth-stimulating effect was noted.