The combination of various heterocyclic systems with a wide range of properties is quite expedient and is, in practice, a justified direction for obtaining biologically active substances, which ultimately forms a favorable basis for the creation of drugs. In recent decades, the attention of scientists has been closely focused on nitrogen-containing heterocyclic compounds. Among such compounds, 1,2,4-triazole and pyrazole occupy a special place. Indeed, on the basis of these systems, a significant number of well-known drugs have been created, which are widely used at the present time. The aim of the work was the synthesis of S-derivatives of 4-amino-5-(5-methylpyrazol-3-yl)-1,2,4-triazole-3-thiol, study of their physical and chemical properties, pre-screening studies with subsequent establishment of the feasibility of further pharmacological studies. Materials and methods. Experimental methods of organic chemistry: synthesis using microwave activation, physical and chemical methods for the analysis of organic compounds (determination of the melting point, elemental analysis, 1H NMR, IR spectroscopy and chromatography-mass spectrometry). Methods for in silico pre-screening studies to establish the biological potential in several synthesized compounds (molecular docking). Results. 10 new S-derivatives of 4-amino-5-(5-methylpyrazol-3-yl)-1,2,4-triazole-3-thiol were synthesized. The structure of the obtained compounds was confirmed by a set of physical and chemical methods of analysis. According to the results of prescreening studies, the main directions of research of biological properties of synthesized compounds were provided. Conclusions. The expediency of using microwave irradiation in the synthesis of a series of S-alkyl derivatives of 4-amino-5-(5-methylpyrazol-3-yl)-1,2,4-triazole-3-thiol had been proved. Based on the results of in silico studies, the expediency of further studies of anti-inflammatory, antifungal and anticancer activities in several synthesized compounds had been substantiated.

A-research concept and design; B-collection and/or assembly of data; C-data analysis and interpretation; D-writing the article; E-critical revision of the article; F-final approval of the article Increased attention to thiadiazole and 1,2,4-triazole derivatives is determined by the extensive structural modification capabilities of heterocyclic system derivatives and their high pharmacological potential. Synthesis of new molecules containing, along with the 1,2,4-triazole moiety, thiadiazole is a promising trend in the field of biologically active substances. The aim of this work was to study the reaction of nucleophilic substitution of 5-((5-amino-1,3,4-thiadiazole-2-ylthio)methyl)-1,2,4-triazole-3-thione with haloalkanes and to establish the structure of the obtained compounds. Materials and methods. Thiosemicarbazide was used as the key starting reagent. As a result of the reaction of the starting material with carbon disulfide in dimethylformamide, a thione was obtained which was further reacted with the iso-propyl ester of the chloroethane acid. The resulting ester was used for further transformations using hydrazinolysis reaction, nucleophilic addition, and intramolecular alkaline heterocyclization. The alkylderivatives of the obtained 5-((5-amino-1,3,4-thiadiazole-2-ylthio)methyl)-1,2,4triazole-3-thione were synthesized by reaction with bromoalkanes, in an alcohol medium with an equimolecular amount of alkali. The structure of the synthesized compounds was confirmed by modern physical-chemical methods of analysis: 1 H NMR spectroscopy, IR spectrophotometry, and elemental analysis data. The individuality of substances was established by means of high-performance liquid chromatography. Results. The method of obtaining 5-((5-amino-1,3,4-thiadiazole-2-ylthio)methyl)-1,2,4-triazole-3-thione has been optimized. The optimal conditions for the synthesis S-alkylderivatives of 5-((5-amino-1,3,4-thiadiazole-2-ylthio)methyl)-1,2,4-triazole-3-thione were determined. The structure of the synthesized compounds was established and their physical properties were investigated. Conclusions. A number of S-alkylderivatives of 5-((5-amino-1,3,4-thiadiazole-2-ylthio)methyl)-1,2,4-triazole-3-thione were obtained and their structure was confirmed by modern physical-chemical methods of analysis. Синтез і властивості 5-(((5-аміно-1,3,4-тіадіазол-2-іл)тіо)метил)-4-феніл-1,2,4-тріазол-3-тіону та його деяких S-похідних А. С. Гоцуля, C. O. Федотов Увага до похідних тіадіазолу та 1,2,4-тріазолу зумовлена широкими можливостями структурної модифікації похідних цих гетероциклічних систем та їхнім високим фармакологічним потенціалом. Синтез нових молекул, що містять тіадіазол поряд із фрагментом 1,2,4-тріазолу,-перспективний напрям у галузі створення біологічно активних субстанцій. Мета роботи-вивчення реакції нуклеофільного заміщення 5-((5-аміно-1,3,4-тіадіазол-2-ілтіо)метил)-1,2,4-тріазол-3-тіону за участю галогеналканів і встановлення структури одержаних сполук. Матеріали та методи. Як ключовий вихідний реагент використали тіосемікарбазид....

Heterocyclic compounds remain the most promising group of compounds, through which the new drugs with characteristic list of properties are successfully created. Examples of this systems are 1,2,4-triazole and pyrazole. The presence in one molecule structure of fragments of two different azaheterocycles is synthetically interesting and allows increasing the probability to obtain biologically active substance with a wide spectrum of action. The aim of the work was to optimize the synthesis conditions and investigate the properties of N-R-2-(5-(5-methyl-1H-pyrazole-3-yl)-4phenyl-4H-1,2,4-triazole-3-ylthio)acetamides in case of change of chemical process conditions. Methods and results. Ethyl 5-methyl-1H-pyrazole-3-carboxylate, which was obtained by known techniques using acetone, diethyl oxalate, sodium methoxide, followed by hydrazine hydrate in equivalent amount, was used as the key starting reagent. The resulting ethyl 5-methyl-1H-pyrazole-3-carboxylate was used to carry out hydrazinolysis reactions and nucleophilic addition of phenyl isothiocyanate with subsequent alkaline heterocyclicization. The synthesized 5-(5-methyl-1H-pyrazol-3-yl)-4-phenyl-4H-1,2,4-triazole-3-thiole was used in alkylation reactions with promising reagents for the design of pharmacophoric fragments. The products of such reaction are N-R-2-(5-(5-methyl-1H-pyrazole-3-yl)-4-phenyl-4H-1,2,4-triazole-3-ylthio)acetamides. The structure of the resulting compounds was confirmed by elemental analysis, 1 H NMR spectroscopy, IR spectrophotometry. The individuality of the substances was determined by thin-layer chromatography and chromatographic mass spectrometry. For synthesized compounds, preliminary screening was performed using the PASS On-line ® software and molecular docking. Conclusions. N-R-2-5-(5-methyl-1H-pyrazole-3-yl)-4-phenyl-4H-1,2,4-triazole-3-ylthio)acetamides are obtained with high yields and purity, their properties are investigated. Синтез, будова та властивості N-R-2-(5-(5-метил-1H-піразол-3-іл)-4-феніл-4H-1,2,4-тріазол-3-ілтіо)ацетамідів А. С. Гоцуля, С. О. Федотов Гетероциклічні сполуки залишаються найбільш перспективною групою, за їхньою допомогою відбувається успішне створення нових лікарських засобів із характерним переліком властивостей. Прикладами таких систем є 1,2,4-тріазол і піразол. Наявність у структурі однієї молекули фрагментів двох різних азагетероциклів є синтетично цікавим і дає змогу збільшити ймовірність одержання біологічно активної субстанції з широким спектром дії. Мета роботи-оптимізація умов синтезу та дослідження властивостей N-R-2-(5-(5-метил-1H-піразол-3-іл)-4-феніл-4H-1,2,4-тріазол-3-ілтіо)ацетамідів при зміні умов перебігу хімічного процесу. Методи та результати. Як ключовий вихідний реагент використали етил 5-метил-1Н-піразол-3-карбоксилат, який одержали за відомими методиками з використанням ацетону, діетилоксалату, натрій метилату та з наступним використанням гідразин гідрату в еквівалентній кількості. Одержаний етил 5-метил-1Н-піразол-3-карбоксилат використали для реакцій гідразинолізу та нуклеофіл...

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A -research concept and design; B -collection and/or assembly of data; C -data analysis and interpretation; D -writing the article; E -critical revision of the article; F -final approval of the article Studies in the field of chemistry and pharmacology of derivatives of thiadiazole and 1,2,4-triazole are promising and relevant, which is associated with significant success in creating new drugs based on them. The combination of these heterocycles in one molecule makes it possible to increase the probability of detecting substances with a certain type of biological activity among the synthesized compounds.The aim of the work was to optimize the synthesis and study of the properties of S-alkyl derivatives of 5-R-4-phenyl-1,2,4-triazole-3thione, containing a thiadiazole fragment in their structure, as well as the prediction of possible biological activity to rating the prospects of further studies in vivo and in vitro. Materials and methods.As a key starting reagent, 3-amino-1-phenylthiourea was used. Using the reaction between the starting reagent and carbon disulfide in DMF, thion was obtained, which was further alkylated with isopropyl chloroacetate. The resulting reaction product was then used for subsequent transformations using hydrazinolysis reactions, nucleophilic addition of phenylisothiocyanate and intramolecular alkaline heterocyclization. A number of S-derivatives of the obtained 4-phenyl-5-((5-phenylamino-1,3,4-thiadiazole-2-ylthio)methyl)-1,2,4-triazole-3-thione were synthesized by the interaction with haloalkanes in the presence of an equivalent amount of alkali in alcoholic medium. The structure of the obtained compounds was confirmed by elemental analysis, 1 H NMR spectroscopy, and IR-spectrophotometry. The individuality of substances was established by high performance liquid chromatography. For the synthesized substances, an individual calculated screening was performed using the PASS Online ® software product.Results. The procedure for preparing 4-phenyl-5-((5-phenylamino-1,3,4-thiadiazole-2-ylthio)methyl)-1,2,4-triazole-3-thione was optimized. The optimal synthesis conditions were determined S-alkylderivatives of 4-phenyl-5-((5-phenylamino-1,3,4-thiadiazole-2-ylthio)methyl)-1,2,4-triazole-3-thiol, the structure was established the obtained substances and their physical properties were studied. With the help of computer-assisted prediction Pass Online ® , a promising direction for further studies of the biological activity of the target reaction products was determined. Conclusions.A series of S-alkylderivatives of 4-phenyl-5-((5-phenylamino-1,3,4-thiadiazole-2-ylthio)methyl)-1,2,4-triazole-3-thione were obtained, the structure of these compounds was confirmed by physical-chemical methods of analysis. At the next stages of the study, it would be planned to establish indicators of the antimicrobial activity of the synthesized substances. Синтез і властивості деяких S-похідних 4-феніл-5-((5-феніламіно-1,3,4-тіадіазол-2-ілтіо)метил)-1,2,4-тріазол-3-тіону C. O. Федотов, А. С. ГоцуляДослідження в галуз...