Synthesis and Antioxidant Activities of Alkylderivatives of 5-(5-Methyl-1h-Pyrazol-3-Yl)-4-Phenyl-4h-1,2,4-Triazole-3-Thiole

Панасенко

2022

АП

Pyrazole and 1,2,4-triazole derivatives play an important strategic role in modern medicine and pharmacy. This fact is due to the significant possibilities of chemical modification and significant pharmacological potential among the derivatives of these heterocycles. The introduction of 1,2,4-triazole and pyrazole fragments into the structure of new substances allows to influence the formation of a certain type of activity. The structural combination of these heterocycles in one molecule increases the likelihood of interaction with various biological targets. At the same time, the creation of condensed systems involving 1,2,4-triazole is undoubtedly scientifically attractive and promising. The aim of the research was to study the conditions for obtaining 3-(5-(4-methoxyphenyl)pyrazol-3-yl)-6-R-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles and studying the properties of these compounds. Materials and methods. The first stage of the synthetic part of the work involved the use of diethyl oxalate and 1-(4-methoxyphenyl)ethan-1-one with the participation of sodium hydride in toluene. The obtained ethyl 4-hydroxy-4-(4-methoxyphenyl)-2-oxobut-3-ethanoate in the next step was used in the process of conversion into ethyl 5-(4-methoxyphenyl)pyrazole-3-carboxylate with the participation of hydrazine hydrate. Further modification of the molecule was the stepwise formation of the structure of 4-amino-5-(5-(4-methoxyphenyl)pyrazol-3-yl)-1,2,4-triazole-3-thiol. The next stage of the work involved the interaction with carboxylic acids in the environment of phosphorus oxychloride. To determine the composition and identify the structure of the isolated substances, 1H NMR and infrared spectra were recorded, as well as qualitative and quantitative indicators of the elemental composition of the synthesized structures were obtained. The individual nature of the presence of substances and the degree of their purity were determined using high performance liquid chromatography. Results. Synthesis of 3-(5-(4-methoxyphenyl)pyrazol-3-yl)-6-R-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles was performed and optimal conditions were determined the process of obtaining these substances. The structure of the products of chemical transformation was confirmed and the results of the study of physical properties were recorded. The results of docking studies allowed to confirm the prospects of the chosen direction of synthetic transformations, which ultimately allowed to determine the biological potential of the obtained compounds. The model enzyme was 14-α-demethylase lanosterol (code 3LD6), information on which was used from the database of the Protein Structures Database (PDB). Conclusions. As a result of the molecular docking, data were obtained that form an idea of a certain level of probability of the effect of synthesized compounds on the activity of 14α-demethylase lanosterol, which justified the need for further study of antifungal activity.

Section: Discussionsupporting

confidence: 57%

Section: Resultsmentioning

confidence: 99%

Section: актуальні питання фармацевтичної і медичної науки та практик...mentioning

confidence: 99%

Section: General Scheme Of Synthesis Of 3-(5-(4-methoxyphenyl)pyrazol...mentioning

confidence: 99%

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Synthesis and properties of some 3-(5-(4-methoxyphenyl)pyrazol-3-yl)-6-R-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles

Панасенко

2022

АП

“…The synthetic part of the study consisted of resynthesis of 5-methylpyrazole and subsequent chemical conversion to 4-amino-5-(5-methylpyrazol-3-yl)-1,2,4-triazole-3-thiol by a known method [9,10].…”

Section: Methodsmentioning

confidence: 99%

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.

Synthesis and properties of 3-(ethylthio)-9-methyl-6-(alkylthio)pyrazolo[1,5-d][1,2,4]triazolo[3,4-f][1,2,4]triazines

Fedotov

2022

АП

The combination of pyrazole and 1,2,4-triazole fragments in one structure makes it possible to achieve some success in creating potential biologically active compounds. Various factors contribute to this process. Among them, we can note the significant possibilities of chemical transformation involving these cycles, the simplicity, and reliability of methods, the creation of molecules with a certain level of bioavailability and the ability to influence a number of biochemical processes. Taking into account the presented facts, the creation of new compounds in a number of pyrazolo-triazole condensed systems is scientifically attractive with endowed features of practical significance and relevance. The aim of the work was to identify optimal conditions for the production of 3-(ethylthio)-9-methyl-6-(alkylthio)pyrazolo[1,5-d][1,2,4]triazolo[3,4-f][1,2,4]triazines and to study the properties of the target reaction products. Materials and methods. The chemical part of the work involved the step-by-step creation of target reaction products in the form of 3-(ethylthio)-9-methyl-6-(alkylthio)pyrazolo[1,5-d][1,2,4]triazolo[3,4-f][1,2,4]triazines. The first stage was aimed at conducting the interaction of diethyloxalate with acetone with the participation of sodium methylate in a methanol medium. Ethyl-2,4-dioxopentanoate was used in the conversion process to 3-methylpyrazole-5-carbohydrazide with the participation of hydrazine hydrate. Further modification of the molecule consisted of the gradual formation of the structure of 4-amino-5-(3-methylpyrazol-5-yl)-1,2,4-triazole-3-thiol. The next step involved the synthesis of 3-ethylthio-5-(3-methylpyrazol-5-yl)-1,2,4-triazole-4-amine. Further conversion included the production of potassium 3-ethylthio-9-methylpyrazolo[1,5-d][1,2,4]triazolo[3,4-f][1,2,4]triazine-6-thiolate and its S-alkyl derivatives along the triazine fragment. Cyclooxygenase-2, lanosterol-14α-demethylase and receptor tyrosine kinase were selected as model enzymes for docking, the crystal structure of which was loaded from the Protein Data Bank. Results. The synthesis of 3-(ethylthio)-9-methyl-6-(alkylthio)-pyrazolo[1,5-d][1,2,4]triazolo[3,4-f][1,2,4]triazines were carried out and the optimal conditions for the production of these substances were determined. The structure of the chemical transformation products was proved and the results of the study of the main physical properties were recorded. The results of virtual studies provided an opportunity to substantiate the prospects of the selected chemical transformation vector, which ultimately made it possible to determine the biological potential of the obtained compounds. Conclusions. Based on the results of the study, information was obtained that gives a certain idea of the possible level of influence of synthesized compounds on the activity of lanosterol-14α-demethylase, which makes it advisable to further search for substances with fungistatic and fungicidal effects.