The thesis is about actual and important problems of modern pharmacy. The path of the search for biologically active substances based on the development of methods for obtaining was investigated and the properties of new derivatives of 5-(1H-tetrazole-1-yl)methyl-4-R-3-thio(amino)-1,2,4-triazoles, which have low-toxicity and high levels of biological activity, was studied. These compounds can be the basis for the creation of original medicines. Furthermore, 5-(1H-tetrazole-1-yl)methyl-4H-1,2,4-triazole-3-yl-1-(5-nitrofuran-2-yl)methanimine, which has high rates of antimicrobial and antifungal activity, is recommended for the in-depth study. 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. Moreover, the careful analysis of the literature revealed a number of issues requiring a solution, among which the purposeful creation of biologically active compounds, derivatives of 5-(1H-tetrazole-1-yl)methyl-4-R-3-thio(amino)-1,2,4-triazole, which exhibit a wide spectrum of biological activity and have lowtoxicity. Known methods of synthesis of 3-thio(amino)-1,2,4-triazoles, which are based on the use of carboxylic acids with alkyl-, aryl- and heteryl-substituents, have been adopted. For creating new derivatives of 1,2,4-triazoles thiones, nitriles, acids inorganic and organic salts, amines, imines with selective reduction of imino-group were synthesized. The next stage of our work it was replaced the Sulfur on the Nitrogen in the third position of the 1,2,4-triazole, which allowed the creation of 3-amino-1,2,4-triazole and their derivatives, imines, amines, thioureasand acetamide. All synthesized substances were purified by the method of crystallization from individual solvents or their mixtures. The structure of synthesized compounds was confirmed by a complex of modern physical-chemical methods of analysis. During the thesis, about 100 new compounds were synthesized in the series of 5-(1H-tetrazole-1-yl)methyl-4-R-3-thio(amino)-1,2,4-triazole which have different types of biological activity. In the first stage of the biological part of the work, the acute toxicity of 41 synthesized derivatives of 5-(1H-tetrazole-1-yl)methyl-4-R-3-thio(amino)-1,2,4-triazole were studied. It has been established that the LD50 of the synthesized substances were in the range of 357-1060 mg / kg. The regularities of the substitution effects on the C4 atom of the nucleus were established 1,2,4-triazole and when replacing Sulfur with Nitrogen in the third position of heterocycle, i.e: the introduction into the fourth position of the 1,2,4-triazole of the phenyl substituent leads to increase in the toxicity of substances. This is the most noticeable in the series of 3-thio derivatives of 1,2,4-triazole. The derivatives of 5-(1H-tetrazole-1-yl)methyl-4-phenyl-3-thio-1,2,4-triazole have high diuretic, antipyretic and hypoglycemic activity rates compared to 3-amino-1,2,4-triazoles; the hydrolysis of nitriles of 2-(5-(1H-tetrazole-1-yl)methyl-4-phenyl-3-thio-1,2,4-triazole-3-ylthio)acetic(propanoic, benzoic) acids are resulted in slight decrease in acute toxicity, and influences high levels of antipyretic activity; the transition to salts of 2-, 4-[5-(1H-tetrazole-1-yl)methyl-4-phenyl-(1,2,4-triazole-3-yl)thiomethyl]benzoic acids are led to increase in the diuretic, actoprotective, antihypoxic and hypoglycemic effects, with acute toxicity of compounds in the 607-977 mg / ml; the substitute of the Sulfur by the amino-group in the third position of the 1,2,4-triazole is led to slight decrease in toxicity, antimicrobial and antifungal activity. According to our research, the primary pharmacological screening for 5-(1H-tetrazole-1-yl)methyl-4H-1,2,4-triazole-3-yl-1-(5-nitrofuran-2-yl)-methanamine were confirmed by diffusion in Agar. It was showed the high rates of antimicrobial and antifungal activity. For this compound, the project of the laboratory synthesis method, the technical requirements for the final product, and the project "Quality control methods" for manufacturing non-sterile medicinal products have been developed and approved. The results of the study of biological activity were decided, laws of the "structure-action" dependence were established, which can be applied for the purposeful search for biologically active compounds among the derivatives of 5-(1H-tetrazole-1-yl)methyl-4-R-3-thio(amino)-1,2,4-triazole. The results of the thesis, which were introduced in the educational and research process of higher educational institutions of Ukraine.
