Synthesis, physical and chemical properties and anxiolytic activity OF 2-(4-(R-arylidenamino)-5-methyl-4H-1,2,4-triazole-3-YL)thio)acetic acids and their salts

Authors

DOI:

https://doi.org/10.15587/2519-4852.2018.135786

Keywords:

1, 2, 4-triazole, 1HNMR, synthesis, heterocyclic compounds

Abstract

It is estimated that 50% of all molecules of medicinal products used in drug therapy are administered as salts. This fact indicates that formation of a medicinal substance salt is an important stage in the development of a medicinal remedy.

Therefore, we believe that the combinatorial synthesis of organic and inorganic salts of derivatives of 1,2,4-triazole has not only theoretical but also practical significance.

The aim of the work is to synthesize and establish the structure of new 2-((4-(R-arylidenamino)-5-methyl-4H-1,2,4-triazole-3-yl)thio)acetic acids and their salts, where R is 2H, 4-dimethylaminobenzyliden, 2-hydroxybenzyliden, 4-hydroxybenzyliden, 4-nitrobenzyliden and their anxiolytic activity.

Materials and methods of research. The physical and chemical properties of the obtained compounds were examined according to the methods presented in the State Pharmacopoeia of Ukraine. The melting temperature was determined on an automatic melting device OptiMelt Stanford Research Systems MPA100 (US production). The elemental composition of the compounds was installed on the elemental analyzer Elementar Vario EL cube (CHNS) (standard - sulfanilamide). Chromatographic mass spectral studies were performed on a gas-liquid chromatograph Agilent 1260 Infinity HPLC equipped with an Agilent 6120 mass spectrometer (ionization in an electrical spray (ESI), 1H NMR spectra were recorded on a Mercury 400 spectrometer, DMSO-D6 solvent, internal standard - tetramethylsilane.

Anxiogenic and anxiolytic activities of the studied compounds in the S. Pellow test.

Research results. 4-(R-arylideneamino)-5-methyl-4H-1,2,4-triazole-3-thiols were taken as initial materials, where R was 2H, 4-dimethylaminobenzylidene, 2-hydroxybenzylidene, 4-hydroxybenzylidene, 4-nitrobenzylidene.

Synthesis of 4-(R-arylideneamino)-5-methyl-4H-1,2,4-triazole-3-thiols, where R was 4-dimethylaminobenzylidene, 2-hydroxybenzylidene, 4-hydroxybenzylidene, 4-nitrobenzylidene, was conducted by adding aromatic aldehyde (4-dimethylaminobenzaldehyde, 2-hydroxybenzaldehyde, 4-hydroxybenzaldehyde, 4-nitrobenzaldehyde) to 4-amino-5-methyl-4H-1,2,4-triazole-3-thiol in acetate acid and heated to dissolution of sediment.

The preparation of 2-((4-(R-arylidenamino)-5-methyl-4H-1,2,4-triazole-3-yl)thio)acetic acids was carried out by adding an aromatic aldehyde to an equivalent amount of 2-((4-amino)-5-methyl-4H-1,2,4-triazole-3-yl)thio)acetic acid in acetic acid medium when heated.

Conclusions. A series of new 2-((4-(R-arylidenamino)-5-methyl-4H-1,2,4-triazole-3-yl)thio)acetic acids were synthesized. The structure of synthesized compounds was established using modern physical and chemical methods of analysis. Some physical and chemical properties of the obtained substances were researched

Author Biography

Yevgean Pruglo, Zaporizhzhia State Medical University Mayakovsky ave., 26, Zaporіzhzhya, Ukraine, 69035

PhD, Associate Professor

Department of Clinical Pharmacology, Pharmacoterapia and Management and Economy of Pharmacy

References

  1. Bhattachar, S. N., Deschenes, L. A., Wesley, J. A. (2006). Solubility: it's not just for physical chemists. Drug Discovery Today, 11 (21-22), 1012–1018. doi: http://doi.org/10.1016/j.drudis.2006.09.002
  2. Šupuk, E., Ghori, M. U., Asare-Addo, K., Laity, P. R., Panchmatia, P. M., Conway, B. R. (2013). The influence of salt formation on electrostatic and compression properties of flurbiprofen salts. International Journal of Pharmaceutics, 458 (1), 118–127. doi: http://doi.org/10.1016/j.ijpharm.2013.10.004
  3. Kumar, L., Amin, A., Bansal, A. K. (2008). Salt selection in drug development. Pharmaceutical Technology, 32 (3), 128–146.
  4. Shcherbyna, R. О. (2017). Synthesis, physical and chemical properties of 2-((4-R-3-(morfolinomethylen)-4H-1,2,4-triazole-5-yl)thio)acetic acid salts. Current issues in pharmacy and medicine: science and practice, 1, 4–8. doi: http://doi.org/10.14739/2409-2932.2017.1.93424
  5. Panasenko, O. I., Salionov, V. O., Knysh, E. G. (2013). Pat. No. 86723 UA. Derivatives of 3-thio-1,2,4-triazole exhibiting actoprotective activity. МPK: A61K 31/00, C07D 249/00. No. u201308222; declareted: 01.07.2013; published: 10.01.2014, Bul. No. 1.
  6. Odyntsova, V. M., Panasenko, O. I., Knysh, Y. H. (2015). Acute toxicity of 2-(5-(adamantane-1-yl)-4R-1,2,4-triazole-3-ylthio) of the acetic acids and their salts’ derivatives. Current issues in pharmacy and medicine: science and practice, 3, 64–66. doi: http://doi.org/10.14739/2409-2932.2015.3.52271
  7. Levchuk, R., Shala, M., Rechko, Yu., Klapotke, T. M., Cudzivo, S. (2017). Sintez i svoystva soley 4,4', 5,5'-tetranitro-1H, 1'H-2,2'-biimidazola – proizvodnykh semikarbazida, 3-amino-1,2,4-triazola i 5-aminotetrazola [Synthesis and properties of 4,4',5,5'-tetranitro-1H,1'H-2,2'-biimidazole salts: semicarbazidium, 3-amino-1,2,4-triazolium, and 5-aminotetrazolium derivatives]. Chemistry of heterocyclic compounds, 53 (6/7), 697–701.
  8. Flyer vario EL cube. Available at: https://www.elementar.de/fileadmin/user_upload/Elementar_Website/Downloads/Flyer/Flyer-vario-EL-cube-EN.pdf
  9. Pellow, S., Chopin, P., File, S. E., Briley, M. (1985). Validation of open: closed arm entries in an elevated plus-maze as a measure of anxiety in the rat. Journal of Neuroscience Methods, 14 (3), 149–167. doi: http://doi.org/10.1016/0165-0270(85)90031-7
  10. Pereira, M. M., de Morais, H., dos Santos Silva, E., Corso, C. R., Adami, E. R., Carlos, R. M. et. al. (2018). The antioxidant gallic acid induces anxiolytic-, but not antidepressant-like effect, in streptozotocin-induced diabetes. Metabolic Brain Disease. doi: http://doi.org/10.1007/s11011-018-0264-9
  11. Seredenin, S. B., Blednov, Yu. A., Andronati, S. A., Pavlovskii, V. I., Yavorsky, A. S. (1995). Pat. No. 2133248 RF. Derivatives of 1,4-benzodiazepine with selective anxiolytic activity. МPK: 7 C07D243/24, A61K31/55. declareted: 12.07.1995, published: 20.07.1999.
  12. Andronati, S. A., Karaseva, T. L., Krivenko, Y. R., Pavlovsky, V. I., Onufrienko, O. V., Shandra, A. A. (2017). Nootropic and Antihypoxic Properties of Novel Derivatives of 1,2-Dihydro-3H-1,4-Benzodiazepin-2-one. Neurophysiology, 49 (6), 405–411. doi: http://doi.org/10.1007/s11062-018-9703-9
  13. Beyer, H., Kröger, C.-F., Busse, G. (1960). Über 1.2.4-Triazole, I Die Reaktion von Thiocarbohydrazid und Thiosemicarbazid mit aliphatischen Carbonsäuren und ihren Derivaten. Justus Liebigs Annalen der Chemie, 637 (1), 135–145. doi: http://doi.org/10.1002/jlac.19606370111
  14. Hoggarth, E. (1952). 2-Benzoyldithiocarbazinic acid and related compounds. Journal of the Chemical Society (Resumed), 4811. doi: http://doi.org/10.1039/jr9520004811
  15. El Ashry, E. S. H., Awad, L. F., Soliman, S. M., Moaty, M. N. A. A., Ghabbour, H. A., Barakat, A. (2017). Tautomerism aspect of thione-thiol combined with spectral investigation of some 4-amino-5-methyl-1,2,4-triazole-3-thione Schiff's bases. Journal of Molecular Structure, 1146, 432–440. doi: http://doi.org/10.1016/j.molstruc.2017.06.002
  16. Bai, Y., Zhao, G., Li, C., Zhao, S., Shi, Z. (2008). Microwave-Enhanced Reactions of 4-Amino-5-merecapto-1,2,4-triazoles with Benzoyl Chloride and Aromatic Aldehydes. Synthetic Communications, 38 (19), 3311–3319. doi: http://doi.org/10.1080/00397910802136649
  17. Pruglo, Ye. S., Panasenko, O. I., Knysh, Ye. G. (2017). Anxiolytic activity of 4-amino-5-methyl-4H-1,2,4-triazole-3-thion N-derivatives and 2-(4-amino-5-methyl-1,2,4-triazole-3-ylthio) acetic acid salts. Farmacom, 2, 24–29.
  18. George, T., Mehta, D. V., Tahilramani, R., David, J., Talwalker, P. K. (1971). Synthesis of some s-triazoles with potential analgesic and antiinflammatory activities. Journal of Medicinal Chemistry, 14 (4), 335–338. doi: http://doi.org/10.1021/jm00286a016

Downloads

Published

2018-06-29

How to Cite

Pruglo, Y. (2018). Synthesis, physical and chemical properties and anxiolytic activity OF 2-(4-(R-arylidenamino)-5-methyl-4H-1,2,4-triazole-3-YL)thio)acetic acids and their salts. ScienceRise: Pharmaceutical Science, (3 (13), 19–25. https://doi.org/10.15587/2519-4852.2018.135786

Issue

No. 3 (13) (2018)

Section

Pharmaceutical Science

License

Copyright (c) 2018 Yevgean Pruglo

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Our journal abides by the Creative Commons Attribution 4.0 International License copyright rights and permissions for open access journals.

Authors, who are published in this journal, agree to the following conditions:

1. The authors reserve the right to authorship of the work and pass the first publication right of this work to the journal under the terms of a Creative Commons Attribution 4.0 International License, which allows others to freely distribute the published research with the obligatory reference to the authors of the original work and the first publication of the work in this journal.

 2. The authors have the right to conclude separate supplement agreements that relate to non-exclusive work distribution in the form in which it has been published by the journal (for example, to upload the work to the online storage of the journal or publish it as part of a monograph), provided that the reference to the first publication of the work in this journal is included.

3. Authors have the right to store the final accepted version of the article in an institutional, thematic, or any other repository to ensure visibility and accessibility.