Objective: The aim of the work was to develop effective methods for the synthesis of biologically active heterocyclic systems containing 1,2,4-triazole and pyrazole. Material and Method: Chemical structures of synthesized compounds were characterized with elemental analysis, IR, 1 H-NMR, LC-MS techniques. The antiradical activity was evaluated using the 2,2-diphenyl-1picrylhydrazyl (DPPH) radical scavenging activity assay. Result and Discussion: Developed optimal methods of obtaining of alkylderivatives of 5-(5-methyl-1Hpyrazol-3-yl)-4-phenyl-4H-1,2,4-triazole-3-thiol. A number of synthesized compounds showed moderate antiradical activity.

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.

Aim. To analyze the carbonyl derivatives of 7-((3-thio-4-R-4H-1,2,4-triazole-5-yl)methyl)theophylline their mother substance was synthesized and its interaction with α-haloketones series was carried out.Methods and results. The physical-chemical properties of the obtained compounds have been studied and their structures have been confi rmed by elemental analysis, infrared spectrometry, 1 H NMR spectrometry, UV spectrophotometry and gas chromatography mass spectrometry. Preliminary computer study of acute toxicity and biological activity has been also carried out. It has been determined that the obtained compounds may exhibit diuretic and analeptic activity and 1,2,4-triazole fragment can theoretically increase it. Conclusion. Preliminary prediction of acute toxicity has showed that the compounds are low-toxic.Синтез і фізико-хімічні дослідження карбонільних похідних 7-((3-тіо-4-R-4H-1,2,4-тріазол-5-іл)метил)теофілінуКниш З метою дослідження карбонільних похідних 7-((3-тіо-4-R-4H-1,2,4-тріазол-5-іл)метил)теофіліну виконали синтез вихідної речовини та її взаємодію з рядом α-галогенкетонів. Досліджені фізико-хімічні властивості одержаних сполук і підтверджена їхня будова за до-помогою елементного аналізу, ІЧ-спектрометрії, 1 Н ЯМР-спектрометрії, УФ-спектрофотометрії та хромато-мас-спектрометрії. Здій-снили попереднє комп'ютерне дослідження гострої токсичності та біологічної активності. Встановили, що отримані сполуки можуть проявляти діуретичну й аналептичну активності, а фрагмент 1,2,4-тріазолу теоретично може підсилювати цю активність. Попереднє прогнозування гострої токсичності показало: сполуки належать до малотоксичних. Синтез и физико-химическое исследование карбонильных производных 7-((3-тио-4-R-4H-1,2,4-триазол-5-ил) метил)теофиллина А. С. Гоцуля, П. С. Князевич, А. И. Панасенко, Е. Г. КнышС целью исследования карбонильных производных 7-((3-тио-4-R-4H-1,2,4-триазол-5-ил)метил)теофиллина проведен синтез исход-ного вещества и его взаимодействие с рядом α-галогенкетонов. Исследованы физико-химические свойства полученных соединений и подтверждено их строение с помощью элементного анализа, ИК-спектрометрии, 1 Н ЯМР-спектрометрии, УФ-спектрофотометрии и хромато-масс-спектрометрии. Проведённое предварительное компьютерное исследование острой токсичности и биологической активности. Установлено, что полученные соединения могут проявлять диуретические и аналептические активности, а фрагмент 1,2,4-триазола теоретически может усиливать эту активность. Предварительное прогнозирование острой токсичности показало, что соединения относятся к малотоксичным.Ключевые слова : 1,2,4-триазол, теофиллин, синтез, ИК-спектрометрия, 1 Н ЯМР-спектрометрия. Запорожский медицинский журнал.

Objective:The aim of the work was to develop effective methods for the synthesis of biologically active heterocyclic systems containing pyrrole, indole and 1,2,4-triazole. In this study, firstly fourteen [1,2,4]triazolo [3,4-b][1,3,4]thiadiazoles compounds requiring for this study were synthesized.Material and Method: Chemical structures of synthesized compounds were characterized with elemental analysis, 1 H NMR, LC-MS techniques. The biological potential of the synthesized substances was estimated by the molecular docking method.Result and Discussion: An optimal method for the synthesis of [1,2,4]triazolo [3,4-b][1,3,4]thiadiazoles has been developed. In molecular modeling studies, the compounds were found to be similar to known drugs in some respects. Besides, the interaction of each molecule in the active site of the crystal structures of cyclooxygenase-1, lanosterol 14-α-demethylase, kinases of anaplastic lymphoma were considered as in silico.

Aim. The research of antimicrobial and antifungal activity of 7-((3-thio-4-R-4H-1,2,4-triazoles-3-yl)methyl)theophylline S-derivatives has been erformed. Methods and results. Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922, Pseudomоnas aeruginosa ATCC 27853, Candida albicans ATCC 885-653 have been taken as a set of standard test-strains. It has been proved that the most active alkyl-derivatives are 7-((3-thio-4-R-4H-1,2,4-triazole-3-yl)methyl)theophylline. Among the synthesized salts, which turned to be active against Staphylococcus aureus, the 2-(5-((theophylline-7-yl)methyl)-4-phenyl-4H-1,2,4-triazole-3-ylthio)acetate ammonium has attracted our attention. Conclusion. The perspective class of compounds for further research on this type of biological activity has been defi ned. Дослідження протимікробної та протигрибкової активності S-похідних 7-((3-тіо-4-R-4Н-1,2,4-тріазол-3-іл)метил)теофіліну