For creating a new biologically active compounds are using a system on which already exist medications. One such system is the core of 1,2,4-triazole. The aim of our work was to study the antimicrobial and antifungal activity new 4-((R-iden)amino)-5-(thiophen-2-ylmethyl)-4H-1,2,4-triazole-3-thiols. The study was conducted according to the method of serial dilutions. As a result of studies new synthesized 4-((R-idene)amino)-5-(thiophene-2-ilmetyl)-4H-1,2,4-triazoles-3-thiols exhibit antimicrobial and antifungal activity. The most active compound that exhibits antimicrobial activity against Staphylococcus aureus is 4-((1-(phenyl)ethylidene)amino)-5-(thiophene-2-ilmetyl)-4H-1,2,4-triazoles-3-thiol and 4-((3-nitrobenzylidene)amino)-5-(thiophene-2-ilmetyl)-4H-1,2,4-triazoles-3-thiol, 4-((4-fluorbenzylidene)amino)-5-(thiophene-2-ilmetyl)-4H-1,2,4-triazoles-3-thiol exhibit antifungal activity level of the comparator fluconazole, compound III, VI exceed its performance.

The rapid development of modern medicine and pharmacy leads to an increase in synthetic drugs. Thus, in the professional literature says that one of the perspective directions are searching for new biologically active compounds including heterocyclic systems and the introduction of the latest in medical, pharmaceutical or veterinary practice. It is known that heterocyclic ring system 1,2,4-triazole moiety is promising for the synthesis of new active ingredients with various kinds of pharmacological actions. The aim of the study was the analysis of literature and patent sources over the past 10 years and the generalization of the results for certain types of biological activity of 1,2,4-triazole. Results of literary analysis show a wide range of biological activity of 1,2,4-triazole-3-tion. The data determine the relevance of further research of derivatives of 1,2,4-triazole in the actoprotective, antimicrobial, antifungal, antihypoxic, hypoglycemic, analgesic, antiinflammatory and others activity in order to find new highly effective in terms of biological substances that can form the basis of new medicines.

The rapid development pace of the pharmaceutical science constantly increases the demand for new kind of medicine featured with high biological activity and non-toxicity at the same time. Setting the aim to enlarge the amount of scientific findings in the domain of biologically active substances, 1,2,4-triazole and theophylline were used as the starting material. These compounds form the basis for the majority of drugs, such as diuretics, antifungal and antibacterial medicaments. The combination of heterocycles put under research demonstrate a repeated probability increase in the variety of activities. Therefore, the relevance of the following study is determined by valuable properties of these substances. Besides that, the presence of a hydrazide element accounts for a high probability level of antimicrobial, particularly anti-tuberculosis activity. In order to identify optimal conditions for the synthesis and physicochemical property research, 2-((5-((theophylline-7'-yl)methyl)-4-R-4H-1,2,4-triazole-3-yl)thio) acetohydrazide ylidenderivatives were obtained. The process of production was carried out through long chain reactions, using the sodium salt of theophylline as a substrate. The conversion is well known being described in many papers. Hydrazide was taken as the starting compound. It was dissolved in water-alcoholic medium while separately, aldehyde was dissolved or mixed in ethyl alcohol as well. The resulting solutions were decanted. The precipitate formed immediately or after a certain period of time, which is likely due to the state of matter of the starting aldehyde. 10 compounds (light-yellow crystalline materials with sharp melting point) were synthesized after that. Their structures and physicochemical properties were confirmed with modern methods of analysis. It is established that the reaction proceeds rapidly with a yield of 77‒95% in water-alcoholic medium at a temperature of about 80 °C.

Chemistry of the 1,2,4-triazole derivatives recently attracts the attention of many scientists, mainly due to the presence of the number of the valuable pharmacological properties. In modern medical practice, there are many examples of successful heterocyclic systems derivatives usage. First of all, it is a group of drugs with antifungal activity (fluconazole, itraconazole, voriconazole, pozakonazol), antidepressant activity (alprazolam, triazolam), anticancer activity (anastrozole, letrozole). But despite the great practical importance of works in this area, the structure of 1,2,4-triazoles-3-thione derivatives have been studied imperfectly. Therefore, the study of this class of compounds is actual now. The aim of this work was to study the UV-spectra of the research compounds in different polarity solvents (water, 95% ethanol, 0,1 M and 1 M sodium hydroxide, 0,1 M and 1 M hydrochloric acid, 0,1 M and 1 M sulfate acid solution, chloroform, isopropanol, acetonitrile and dioxane) for structure–spectral data relationship establishing. Spectrophotometer SPECORD 200-222U214 was used to study the UV-spectra of the analyzed compounds and to measure their intensity. During the research, it was found that the electronic spectra of 7-((3-thio-4-methyl-1,2,4-triazoles-5-yl)methyl)theophylline, 7-((3-thio-4-ethyl-1,2,4-triazolе-5-yl)methyl)theophylline and 7-((3-thio-4-phenyl-1,2,4-triazolе-5-yl)methyl)-theophylline were characterized by maximums in the short-wave (203–235 nm) and medium-wavе part (250–272 nm) of UV-spectrum. Due to the presence of the methylene fragment in investigated molecules, which connects the purine cycle with 1,2,4-triazole, absorbtion maximums were caused by π→π*-electron jumping of the corresponding type 1La and 1Lb.

Chemistry of heterocyclic compounds is one of the most popular sector in organic chemistry. Scientists allocate among them a class of derivatives of 1,2,4-triazole. This class of compounds attracts attention his broad spectrum of biological activity. There are antiviral, anti-inflammatory, anti-tubercular, antimicrobial, antioxidant, actoprotective, anti-cancer and other activities. The derivatives of 1,2,4-triazole have one more important advantage. It is low toxicity. This properties do this class of derivatives promising for researches their chemical structure and biological activity and purposeful search of biologically active substances. The purpose of the work is synthesis of 5-(4-(tert-butyl)phenyl)-4-((R)amino)-4H-1,2,4-triazoles-3-thiols from appropriate ylidene derivatives of 4-amino-5-(4 (tert-butyl)phenyl)-4H-1,2,4-triazoles-3-thiol and research of their physical and chemical properties. The objects of research were 10 new compounds, derivatives of 4-amino-5-(4-(tert-butyl)phenyl)-4H-1,2,4-triazoles-3-thiol. These compounds are the crystal substances which are odorless, insoluble in water and soluble in organic solvents. Investigation of the physical and chemical properties of this compounds was carried out according to the methods listed in the State Pharmacopoeia of Ukraine. The melting temperature of synthesized compounds was determined by device OptiMelt Stanford Research Systems MPA100. The structure of the compound was confirmed by 1H-NMR spectroscopy (Mercury 400) and gas chromatography-mass spectrometry (Agilent 1260 Infinity HPLC). 10 new compounds, derivatives of 4-amino-5-(4-(tert-butyl)phenyl)-4H-1,2,4-triazoles-3-thiol, were synthesized in a study. The chemical structure of the new compounds was confirmed by modern instrumental methods of analysis. Results of the done work can be use in the future search of biologically active substances.

The achievements of modern pharmaceutical chemistry allow to develop a wide range of potential new drugs. However, their success in clinical practice depends on their safety. Therefore, the presence of evidence of their safety and efficacy is an integral part of any research. The aim of our study was to investigate acute toxicity of synthesized 1,2,4-triazoles derivatives, studying behavioral reactions to toxic doses and dependence "structure – action". Methods. To install middle lethal dose (LD50) the substance was administered intraperitoneally as an aqueous suspension stabilized by Tween-80. The substance was administrated once to four groups of laboratory animals (white nonlinear rats), 2 animals in each group. Multiple doses were administered, including the dose which does not cause the death of any animal and the dose which causes the death of all animals in the group. After administration of the compounds we conducted surveillance for two weeks to all animals who stayed alive. Results. The least toxic compound among the studied 4-(R-benzylidenamino)-5-methyl-4H-1,2,4-triazoles-3-thiones was compound 1 with an index of 840 mg/kg, which contains 4-methoxybenzilidene substituent on N4-nitrogen atom and the most toxic was compound 5, which has 4-brombenzilidene substituent at the same prosition (LD50 – 284 mg/kg). So we see that replacing bromine atom leads to the reduction of toxic properties. So we can assume that the introduction of a halogen atom to benzilidene phenolic core substituent increases the toxic properties of the synthesized compounds. An interesting pattern is observed for compounds 2–4, which contain two methoxy substituents, and their LD50 almost did not changed and range from 764 to 790 mg/kg. Conclusions. The study has found that 4-(R-benzylidenamino)-5-methyl-4H-1,2,4-triazol-3-tiones belonging to IV Class of toxicity. In addition, these compounds can be subjected to further biological study.

Introduction. Nowadays 1,2,4-triazole-3-thiol furan derivatives have established themselves as a separate class of promising bioactive compounds. Presented substance is practically non-toxic and exhibits various kinds of pharmacological activity. New original drug «Tryfuzol» in two dosage forms (1% injectable solution and 1% solution for oral administration) triumphantly entered the practice of the national veterinary. The most attractive in pharmacological aspects are water-soluble compounds 5-(furan-2-yl)-4R-1,2,4-triazole-3-thiols. Other classes of 1,2,4-triazole-3-thiol furan derivatives are also in considerable scientific interest. However, despite the presence of a sufficiently large number of publications, the issue of pharmacological tests systematization of the 1,2,4-triazole-3-thiol furan derivatives is still open. In this way the aim of our work was the systematization of the available sources of domestic authors. Materials and methods. Our work presents the results of systematic analysis of the available domestic literature related to the study of pharmacological properties of 1,2,4-triazole-3-thiol furan derivatives. Research results. It is known that 1,2,4-triazole-3-thiol furan derivatives have wide range of properties and biological activities. Thioacetate salts of corresponding acids show the highest results. The authors investigated the properties of water-soluble compounds of 1,2,4-triazole-3-thiol furan derivatives. Another group of compounds was investigated on hypoglycemic activity. It was established that the most active were piperidine 2-(5-(furan-2-yl)-4-(3-methylphenyl)-1,2,4-triazol-3-ylthio) acetate and piperidine 2-(5-(furan-2-yl)-4-phenyl-1,2,4-triazol-3-ylthio) acetate. Conclusion. The scientific potential of the domestic pharmaceutical industry has no doubts for today. The literature analysis of Russian authors proves the obvious prospect of further research of biologically active compounds among 1,2,4-triazole-3-thiol furan derivatives.

Aim. The research of biologicaly active molecules among the number of fluorphenyl derivatives of 1,2,4-triazoles-3-thioles is an important task for modern pharmaceutical science. The reactions of the 5-benziliden-2-(3-fluorphenyl)triazoles-[3,2-v]-1,2,4triazoles-6-(5H)-ones recovery has been carried out with the aim to expand the arsenal of potential pharmacologically active structures.Methods and results. Structure of the synthesized molecules has been revealed using complex of physical-chemical methods of analysis, identity has been confirmed by chromatography.Conclusion. For the first time according to the results of complex analysis it was proved that recovery of the relevant 5-benziliden-2-(3-fluorphenyl)triazoles-[3,2-v]-1,2,4-triazoles-6-(5H)-ones appears with bicyclical structure destruction and formation of unsaturated spirits. Finally the structure of molecules has been confirmed with X-ray diffraction analyzes.

Aim. Research of the acute toxicity of new compounds could prevent the development of compounds with high pharmacological activity, which exhibit undesirable pharmacological properties. Therefore, on the first stages of research the study of the acute toxicity of new compounds is quite actual. Methods and results. For further research of the pharmacological properties of the synthesized compounds the acute toxicity of 5-thio-substituted 3-(5-bromofuran-2-yl)-4-ethyl-(4H)-1,2,4-triazole derivatives has been examined on white nonlinear rats by V. B. Prozorovskiy method (2007). The comparative evaluation of researched parameters for newly synthesized 3-(5-bromofuran-2-yl)-4-ethyl-4H-1,2,4-triazole-5-thione derivatives and already applicable drugs, which are 1,2,4-triazole derivatives has been performed. Conclusion. It has been established that the acute toxicity of the test compounds is in the ranges from 331 to 713 mg/kg, which indicates their low toxicity and classifies them to the IV-th class of toxicity.

Aim. Modern medicine widely applies drugs from the group of 1,2,4-triazole (fluconazole, triazolam, alprazolam, letrozole and others) in the practice. This class of compounds has synthetic origin and a broad spectrum of biological activity, and is characterized by low toxicity. It is known that the presence of triazole ring in the molecule effects on the range and intensity of biological action. Methods and results. In order to create new biologically active compounds in a series of ylidene derivatives of 4-amino-5-(4-tretbutilfenil)-4H-1,2,4-triazole-3-thiol proposed preparative methods of synthesis 5-(4-tretbutilfenil) -4-R-4H-1,2,4-triazole-3-thiols have been proposed. The structure of synthesized compounds has been confirmed by 1H NMR-spectroscopy, chromatography-mass spectrometry and elemental analysis. Conclusion. This indicates the possibility of using these substances to further biological studies.

Aim. Research of the acute toxicity of new compounds could prevent the development of compounds with high pharmacological activity, which exhibit undesirable pharmacological properties. Therefore, on the first stages of research the study of the acute toxicity of new compounds is quite actual. Methods and results. For further research of the pharmacological properties of the synthesized compounds the acute toxicity of 5-thio-substituted 3-(5-bromofuran-2-yl)-4-ethyl-(4 H )-1,2,4-triazole derivatives has been examined on white nonlinear rats by V. B. Prozorovskiy method (2007). The comparative evaluation of researched parameters for newly synthesized 3-(5-bromofuran-2-yl)-4-ethyl-4 H -1,2,4-triazole-5-thione derivatives and already applicable drugs, which are 1,2,4-triazole derivatives has been performed. Conclusion . It has been established that the acute toxicity of the test compounds is in the ranges from 331 to 713 mg/kg, which indicates their low toxicity and classifies them to the IV- th class of toxicity.

Aim. Nowadays, every seventh person over forty years tends to glucose tolerance disturbance. In order to determine glucose tolerance of newly synthesized salts of 2-(5-adamantane-1-yl)-4-R-1,2,4-tirazoles-3-yltio)acetic acids, pharmacological screening of the influence of corresponding salts on a glucose level in the glucose tolerance test has been carried out. Methods and results. It was found, that there are some regularities between the chemical structure of the obtained compounds and their pharmacological activity. Conclusion. This indicates the prospects of further researches of the received compounds.

Aim. The research of anti-inflammatory activity of 2-(5-((theophylline-7’-yl)methyl)-4-R-4H-1,2,4-triazole-3-ylthio)acetic acid’s salts has been conducted on the «formalin-induced edema of the rats’extremities» model of acute inflammation.Methods and results. Inflammatory reaction has been modeled using 2,0% aqueous formalin solution. Diclofenac sodium has been used as a reference drug. The research results have been processed by modern statistical methods of analysis. As the research results show, the most active are 2-(5-((theophylline-7’-yl)methyl)-4-R-4H-1,2,4-triazole-3-ylthio)acetic acid and it’s diethyletanolammonium salt. Conclusion. Among studied substances the piperidine 2-(5-((theophylline-7’-yl)methyl)-4-phenyl-4H-1,2,4-triazole-3-ylthio)acetateshould also be noted, as it shows high anti-inflammatory activity.