Ignatova T. Synthesis, physical-chemical and biological properties of 4-R-5-phenethyl-2,4-dihydro-3H-1,2,4-triazole-3-thions and their substitutes

The thesis is one of the most relevant work in the pharmaceutical industry, which contains the main aspects of synthesis, study of physical-chemical, and search for new biologically active compounds based on the 5-phenethyl-4-R-3-thio(amino)-1,2,4-triazole. The test compounds have low toxicity and high pharmacological action, which can be new promising drugs. Іn-depth study recommended 1-(benzo[d][1,3]dioxol-5-yl)-N-(5-phenethyl-4H-1,2,4-triazole-3-yl)methanimine, which has high antihypoxic effects. For this compound, the project of laboratory synthesis method, technical requirements for the final product, and the project "Quality control methods" for the manufacture of non-sterile medicinal products have been developed and approved. As a result of the research, the known methods of synthesis of 3-thio(amino)-1,2,4-triazoles were adapted, which use carboxylic acids as starting materials with alkyl-, aryl- and heteryl substituents. The direction of the creation of new compounds in the series of 5-phenethyl-4-R-3-thio(amino)-1,2,4-triazole has been proposed, the synthesis of about 100 compounds did not describe in the literature. At first, optimal conditions for acid and alkaline hydrolysis of2-[{5-phenethyl-4-R-(1,2,4-triazole-3-yl)q1rthio}(aceto-, propano-, benzo)]nitriles were described and selected. Preparative methods of synthesis of previously unknown substances were offered by 5-phenethyl-4-R-1,2,4-triazole-3-thiones, nitriles, iminoesters, and salts of 2-[5-phenethyl-4-R-(1,2,4-triazole-3-yl)thio]ethanoic(propanoic, benzoic)acids,6-(5-phenethyl-4-R-(1,2,4-triazole-3-yl)thio)pyridin-3-amines, the corresponding imines and their selective reduction products. To create new biologically active compounds, an attempt was made to replace the sulfuratom in the third position of the nucleus 1,2,4-triazole with a nitrogenatom, which allowed to obtain 5-phenethyl-1,2,4-triazole-3-amine and its methanimines, amines, thiourea. Through the GUSAR-online program, acute toxicity has been predicted for previously synthesized 5-phenethyl-4-R-3-thio(amino)-1,2,4-triazole and its derivatives. Antimicrobial and antifungal, antipyretic, hypoglycemic, antioxidant and antihypoxic effects were studied, which allowed to establish patterns between the nature of substitutes and the detection of biological activity. Keywords: 5-phenethyl-4-R-3-thio(amino)-1,2,4-triazole derivatives, modification, synthesis, physical-chemical properties, biological activity.