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

Abstract

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

“…1 H NMR spectra of synthesized compounds (8)(9)(10)(11)(12)(13)(14) were recorded in accordance with the proposed structures. Thus, the signal of protons of the NH group of the pyrazole cycle was located at 13.05-13.07 ppm in the form of a singlet.…”

“…The resulting sediment was filtered and dried. [1,2,4]triazolo [3,4-b] [1,3,4]thiadiazoles (8)(9)(10)(11)(12)(13)(14) To 0.01 mol of the initial 4-amino-5-(5-(4-methoxyphenyl) pyrazole-3-yl)-1,2,4-triazole-3-thiol, 0.01 mol of the corresponding carboxylic acid (benzoic, 2-methoxy-, 3-methoxybenzoic, 2-chlorobenzoic, 2-bromo-5-methoxybenzoic, 2-bromo-4-fluorobenzoic, 2-bromo-5-nitrobenzoic) and 15 ml of POCl 3 was added and heated for 3 hours at the temperature of 80 °C. After cooling, the solution was poured onto the ice.…”

“…The combination of different heterocyclic fragments with pharmacophore properties in one molecule makes it possible to use in practice the basic principles of the hybrid pharmacophore method for constructing molecules that are promising from the point of view of Pharmacology [1][2][3][4][5][6][7][8][9]. This approach allows you to achieve the necessary pharmacological effect, influence the indicators of toxicity and selectivity of action [10][11][12][13][14][15]. Recently, there has been an increased interest in the study of condensed heterocyclic systems.…”

“…The compounds crystallized from concentrated ethanoic acid. The substances were crystalline white (8)(9)(10)(11), yellow (12,14), and bright yellow (13). These substances were practically insoluble in water, soluble in organic solvents.…”

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

“…The stepwise formation of the structure of the Intermediate 3-ethylthio-5-(3-methylpyrazol-5-yl)-1,2,4-triazole-4-amine and the properties of all preintermediates were described in previous works [14,15]. The synthesis of potassium 3-…”