Synthesis and physical-chemical research of 7-((3-thio-4-r-4h-1,2,4-triazole-5-yl)methyl)theophylline carbonyl derivatives

Current Issues in Pharmacy and Medicine: Science and Practice

Knysh

2020

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 The combination of derivatives of 1,2,4-triazole and theophylline creates fertile soil for biologically active substances. The use of these heterocyclic systems allows the use of simple chemical modification methods and available reagents. This determines the relevance of the chosen direction of scientific research. The aim of the work was to study synthesis methods and study the properties of heterocyclic systems containing theophylline and 1,2,4-triazole fragment in their structure, create a chemical variety that was interesting from a scientific point of view and was promising in the search for biologically active substances. Materials and methods. Theophylline was used as the starting material. Using alkylation reactions, hydrazinolysis, interaction with a carbon disulfide followed by heterocyclization with an excess of hydrazine hydrate, 7'-((4-amino-5-thio-1,2,4-triazole-3-yl)methyl) theophylline was obtained. The following stages of the chemical conversion included alkylation reactions with haloalkanes, the formation of azomethine compounds by reaction with aromatic aldehydes, and the reaction with aromatic carboxylic acid chlorides. The structure of the obtained compounds was confirmed by data of elemental analysis, 1 H NMR spectroscopy and IR-spectrophotometry. The individuality of substances was established by using high performance liquid chromatography with diode-array and mass spectrometric detection. Results. S-alkylderivatives of 7'-((4-amino-5-thio-1,2,4-triazole-3-yl)methyl)-theophylline, Schiff bases and carboxamides were synthesized, their structure was proved, and physical properties were investigated. The synthesized compounds have been subjected to the in silico molecular docking study against the kinases of anaplastic lymphoma by using the 2XP2 ligand, lanosterol 14-α-demethylase by using the 3LD6 ligand, cyclooxygenase-2 by using the ligand 4Z0L which were downloaded from the protein data bank (PDB). Conclusions. Molecular docking has shown the ability of the synthesized compounds to influence the kinase activity of anaplastic lymphoma, cyclooxygenase-2 and lanosterol-14-α-demethylase. Синтез, будова та властивості похідних 7'-((4-аміно-5-тіо-1,2,4-тріазол-3-іл)метил)теофіліну А. С. Гоцуля, Є. Г. Книш Поєднання похідних 1,2,4-тріазолу й теофіліну створює підґрунтя для одержання біологічно активних речовин. Застосування цих гетероциклічних систем дає змогу використовувати нескладні методи хімічної модифікації та доступні реагенти. Це зумовлює актуальність обраного напряму наукових пошуків. Мета роботи-дослідження методів синтезу та вивчення властивостей гетероциклічних систем, що містять у своїй структурі теофілін і 1,2,4-тріазольний фрагмент, створюють цікаве з наукового погляду хімічне різноманіття та є перспективними в галузі пошуку біологічно активних субстанцій. Матеріали та методи. Як вихідну...

Section: актуальные вопросы фармацевтической и медицинской науки и прmentioning

confidence: 64%

Section: актуальные вопросы фармацевтической и медицинской науки и прmentioning

confidence: 99%

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Synthesis, structure and properties of 7-((4-amino-5-thio-1,2,4-triazole-3-yl)methyl)-theophylline derivatives

Current Issues in Pharmacy and Medicine: Science and Practice

Knysh

2020

“…Propyl 2-(theophylline-7'-yl)acetate, 2-(theophylline-7'-yl)acetohydrazide, 2-(2-(theophylline-7'-yl) acetyl)-N-ethylhydrazynecarbothioamide, 7'-((3-thio-4-ethyl-4Н-1,2,4-triazoles-5-yl)methyl)theophylline have been obtained in accordance with methods, described in the literature [1,9].…”

Section: Methodsmentioning

confidence: 99%

“…Therefore, combining it with different nature radicals may be interesting for further research [3,9]. Thus, increasing the probability of new pharmacological effects appearance and strengthening of existing is possible.…”

Section: а с гоцуляmentioning

confidence: 99%

Synthesis, physical and chemical research of alkyl-, heterylderivatives of 7'-((4-ethyl-5-thio-4H-1,2,4-triazoles-3-yl)methyl)theophylline

Current Issues in Pharmacy and Medicine: Science and Practice

2016

Aim. To analyze the alkyl-, heterylderivatives of 7'-((4-ethyl-5-thio-4H-1,2,4-triazoles-3-yl)methyl)theophylline their mother substance has been synthesized and its interaction with halogenalkane and halogenheteryle has been carried out.Methods and results. The physical and 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.Results and their discussion. Theophylline was used as starting substance from which through series successive stages of transformation (electrophilic substitution reaction, hydrazinolysis, etherifi cation and intramolecular alkaline heterocyclisation) starting thiol and alkyl derivatives were obtained. Alkyl derivatives were obtained in propanol-1 with heating. Synthesized substances were crystallized from methanol.Signals of methyl groups of theophylline, N 7 -CH 2 -groups, thioalkyl fragments are fi xed in 1 H NMR spectrum of obtained compound. Protons of the S-alkyl fragments resonate in a strong fi eld as a multiplet in area 1.53-1.01 ppm. Protons of N-C 2 H 5 fragment are fi xed also as a multiplet at 1.74-1.62 ppm. CH 2 -group is presented by protons signals as a singlet at 5.71 ppm. Protons of CH 3 -group of the xanthine sinton resonate at 2.95 and at 3.25 ppm.Personality of the compounds has been established using chromato-mass spectrometry. Conclusion. 13 New compounds have been obtained and their structure has been confi rmed.Indicators of computer evaluation of synthesized compounds using the PASS program have been researched. By means of prediction, results identifi ed the most perspective compounds for testing the biological activity in vitro. During the analysis of obtained results, it was able to establish that obtained compounds possess different types of biological activity. Diuretic and analeptic activities dominate among the most likely types of that predicted activities for all 13 compounds. Синтез і фізико-хімічні дослідження алкіл-та гетерилпохідних 7'-((4-етил-5-тіо-4Н-1,2,4-тріазол-3-іл)метил)теофіліну А. С. ГоцуляМета роботи -для дослідження алкіл-та гетерилпохідних 7'-((4-етил-5-тіо-4Н-1,2,4-тріазол-3-іл)метил)теофіліну здійснити синтез вихідної речовини й дослідити її взаємодію з галогеналканами та галогенгетерилами.Матеріали та методи. Як вихідну сполуку використали теофілін, з якого через ряд послідовних стадій (реакції електро-фільного заміщення, гідразинолізу, етерифікації та внутрішньомолекулярної лужної гетероциклізації) отримали вихідний тіол та його алкілпохідні. Алкілпохідні були синтезовані в середовищі пропанолу-1 при нагріванні. Синтезовані сполуки криста-лізовано в середовищі метанолу.Результати. Досліджено фізико-хімічні властивості сполук, що отримали, їхня будова доведена за допомогою елементного аналізу, ІЧ-спектрометрії, 1 Н ЯМР-спектрометрії, УФ-спектрофотометрії та хро...

Synthesis and properties of S-derivatives of 4-amino-5-(5-methylpyrazol-3-yl)-1,2,4-triazole-3-thiol

Fedotov

2021

АПФМНП

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.