Approach to synthesis and study of pharmacological effects of new 1,3,5-triazine derivatives

Introduction. Among the derivatives of 1,3,5-triazine, compounds with different biological activity are known, but there are few drugs of this structure on the pharmaceutical market. Thus, the production of new medicines based on a triazine core, as well as the study of their biological activity is an urgent direction. Objective: synthesis of new 1,3,5-triazine derivatives using the reaction of recycling of 2,5-disubstituted-4-hydroxy-6H-1,3-oxazine-6-ones by 1,3-binucleophiles to obtain different substituents at positions 2,4,6 in one stage, as well as assessment of acute toxicity, diuretic activity in silico and in vivo for synthesized products. Material and methods. The target compounds were obtained as a result of the interaction of 2,5-disubstituted-4-hydroxy-6H-1,3-oxazine-6-ones and S-methylisothiourea of hemisulfate in the presence of an equimolar amount of sodium methylate in a methanol medium. Prediction of acute toxicity of the studied compound was carried out using the local version of the GUSAR software. Computer screening of biological activity was carried out using the PASS program. Acute toxicity in vivo was determined on white male mice. For experimental evaluation of the diuretic activity of the obtained compounds in vivo, the Taylor, Topliss model was included in the work. Results. 2-(methylsulfanyl)-4-(4-nitrophenyl)-6-ethyl-1,3,5-triazine, 2-(methylsulfanyl)-4-(4-nitrophenyl)-6-(pentane-1-yl)-1,3,5-triazine were obtained with a yield of 72% and 69%, respectively. The structure of the obtained compounds was proved using 1H and 13C NMR spectroscopy. The predicted and experimental data of acute toxicity correlate with each other, and the studied compounds belong to the class "low-toxic". During the screening of biological activity using the PASS program, data on the estimated diuretic activity were obtained. Studies of biological activity in vivo have shown that the target compounds have pronounced diuretic activity. Conclusion. New compounds have been synthesized, their structure has been proved using modern physico-chemical analysis methods. The results of computer prediction made it possible to determine the potential class of toxicity and identify potential biological activity. With the help of experimental pharmacological studies, it has been proved that the studied compounds have low toxicity and exhibit pronounced diuretic activity.