Synthesis and properties of S-derivatives of 4-amino-5-(5-methylpyrazol-3-yl)-1,2,4-triazole-3-thiol
DOI:
https://doi.org/10.14739/2409-2932.2021.3.243176Keywords:
5-methylpyrazole, 1,2,4-triazole, synthesis, properties, molecular dockingAbstract
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.
References
Boraei, A. T. A., El Ashry, E. S. H., & Duerkop, A. (2016). Regiose-lectivity of the alkylation of S-substituted 1,2,4-triazoles with dihaloalkanes. Chemistry Central Journal, 10, 22. https://doi.org/10.1186/s13065-016-0165-0
Varynskyi B., Kaplaushenko A., & Parchenko V. (2018). Electrospray ionization mass spectrometry fragmentation pathways of salts of some 1,2,4-triazolylthioacetate acids, the active pharmaceutical ingredients. Asian Journal of Pharmaceutical and Clinical Research, 11(10), 303-312. https://doi.org/10.22159/ajpcr.2018.v11i10.16564
Varynskyi, B. (2019). PIPEridinium 2-((5-(furan-2-yl)-4-phenyl-4h-1,2,4-triazol)-3-yl) acetate forced degradation study. Ankara Universitesi Eczacilik Fakultesi Dergisi, 43(2), 117-134. https://doi.org/10.33483/jfpau.480073
Hulina, Yu. S., & Kaplaushenko, A. G. (2018). Synthesis, physical and chemical properties of 5-((1H-tetrazole-1-yl)methyl)-4-R-4H-1,2,4-triazole-3-thiols and their chemical transformations. Russian Journal of Biopharmaceuticals, 10(1), 26-30.
Samelyuk, Y. G., & Kaplaushenko, A. G. (2014). Synthesis of 3-alkylthio(sulfo)-1,2,4-triazoles, containing methoxyphenyl substituents at C5atoms, Their antipyretic activity, Propensity to adsorption and acute toxicity. Journal of Chemical and Pharmaceutical Research, 6(5), 1117-1121.
Can, N. Ö., Acar Çevik, U., Sağlık, B. N., Levent, S., Korkut, B., Öz-kay, Y., & Koparal, A. S. (2017). Synthesis, Molecular Docking Studies, and Antifungal Activity Evaluation of New Benzimidazole-Triazoles as Potential Lanosterol 14α-Demethylase Inhibitors. Journal of Chemistry, 2017, 9387102. https://doi.org/10.1155/2017/9387102
Kaur, R., Dwivedi, A. R., Kumar, B., & Kumar, V. Recent (2016). Developments on 1,2,4-triazole nucleus in anticancer compounds. Anti-Cancer Agents in Medicinal Chemistry, 16(4), 465-489. https://doi.org/10.2174/1871520615666150819121106
Gotsulya, A. S., Panasenko, O. I., Knysh, Ye. G., & Knyazevich, P. S. (2015). Synthesis and physical-chemical research of 7-((3-thio-4-R-4H-1,2,4-triazole-5-yl)methyl)theophylline carbonyl derivatives. Zaporozhye medical journal, (3), 103-107. https://doi.org/10.14739/2310-1210.2015.3.44510
Hotsulia, A. S. Syntez, peretvorennia, fizyko-khimichni ta biolohichni vlastyvosti v riadu N- ta S-zamishchenykh 1,2,4-tryazol-3-tiolu, yaki mistiat yadro pirolu, pirazolu, purynu ta ksantynu [Synthesis, transformation, physicochemical and biological properties in number N- та S-substituted 1,2,4-triazole-3-thiol, which contain the core of pyrrole, pyrazole, purine and xanthine (Doctoral dissertation)]. Zaporizhzhia State Medical University, Zaporizhzhia. [in Ukrainian].
Gotsulya A. S. (2020). Synthesis and antiradical activity of alkyl derivatives of 5-(5-methyl-1H-pyrazol-3-yl)-4-phenyl-4H-1,2,4-triazole-3-thiol. Journal of Faculty of Pharmacy of Ankara University, 44(2), 211-219. https://doi.org/10.33483/jfpau.6161161
Abdelall, E., Lamie, P. F., Ahmed, A., & El-Nahass, E. S. (2019). COX-1/COX-2 inhibition assays and histopathological study of the new designed anti-inflammatory agent with a pyrazolopyrimidine core. Bioorganic chemistry, 86, 235-253. https://doi.org/10.1016/j.bioorg.2019.01.031
Odds, F. C., Brown, A. J., & Gow, N. A. (2003). Antifungal agents: mechanisms of action. Trends in microbiology, 11(6), 272-279. https://doi.org/10.1016/s0966-842x(03)00117-3
Kummari, L. K., Butler, M. S., Furlong, E., Blundell, R., Nouwens, A., Silva, A. B., Kappler, U., Fraser, J. A., Kobe, B., Cooper, M. A., & Ro-bertson, A. (2018). Antifungal benzo[b]thiophene 1,1-dioxide IMPDH inhibitors exhibit pan-assay interference (PAINS) profiles. Bioorganic & Medicinal Chemistry, 26(20), 5408-5419. https://doi.org/10.1016/j.bmc.2018.09.004
Othman, A. A., Kihel, M., & Amara, S. (2019). 1,3,4-Oxadiazole, 1,3,4-thiadiazole and 1,2,4-triazole derivatives as potential antibacterial agents. Arabian Journal of Chemistry, 12(7), 1660-1675. https://doi.org/10.1016/j.arabjc.2014.09.003
Biovia. (2019). Discovery Studio Visualizer, V19.1.0.18287 [Software]. http://www.3dsbiovia.com/
ChemAxon. (2015). MarvinSketch, Version 6.3.0. [Software]. http://www.chemaxon.com
Worldwide Protein Data Bank. (n.d.). Protein Data Bank (PDB) [Da-tabase]. http://www.pdb.org
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