Synthesis of 5-acetyl-2-amino-1,4-diaryl-6-oxo-1,4,5,6-tetrahydropyridine-3-carbonitriles. rotamerium in the series of tetrahydropyridine-3-carbonitriles

It was found that the interaction of arylmethylidenemalonodinitrile with N-arylamides of acetoacetic acid proceeded in the presence of piperidine or triethylamine at room temperature. According to IR and NMR (1^H, ¹³C) spectroscopy, in both cases, 5-acetyl-2-amino-1,4-diaryl-6-oxo-1,4,5,6-tetrahydropyridine-3-carbonitriles are formed with yields of 47-75%. According to NMR spectroscopy data, if the aromatic ring of the amide part of the molecule contains an ortho-substituent in the initial compounds, then the products obtained in solution are in the form of two rotamers. The fact that these compounds exist in the form of two rotamers is also evidenced by the fact that when two methyl substituents are simultaneously present in the ortho- and para-positions of the compound, the chemical shift of the para-substituent protons does not change. Study of antitumor activity has shown that the synthesized substances exhibit both pronounced activity, suppressing tumor growth by 64% (P <0.05), and moderate antitumor activity (inhibiting tumor growth by 47-55% P <0.05, in relation to sarcoma -180. Study of the acute toxicity of these compounds has shown that the test substances are relatively low toxic. Their absolute lethal dose (LD 100) is higher than 1500 mg / kg