Synthesis and properties of 2-(4-phenyl-5-(((5-phenylamino-1,3,4-thiadiazole-2-yl)thio)methyl)-1,2,4-triazole-3-yl)thio)ethanoic acid and its salts
DOI:
https://doi.org/10.14739/2409-2932.2020.3.216175Keywords:
thiadiazole, 1, 2, 4-triazole, physical-chemical properties, molecular dockingAbstract
Analysis of the literature over the past decade has shown that the chemistry of 1,2,4-triazole and 1,3,4-thiadiazole attracts considerable interest from scientists around the world because of the many valuable properties of compounds of this class. Bibliosemantic analysis shows that the nuclei of 1,2,4-triazole and 1,3,4-thiadiazole are fragments of a number of known drugs and biologically active compounds. That is why the synthesis and study of physical-chemical, biological properties of salts and acids containing these heterocyclic fragments are quite relevant both from a theoretical and practical point of view.
The aim of the work was to targeted synthesis of 2-((4-phenyl-5-((5-phenylamino-1,3,4-thiadiazole-2-yl)thio)methyl)-1,2,4-triazole-3-yl)thio)ethanoic acid and its salts, as well as the establishment of physical-chemical properties of the synthesized compounds. Estimation of the biological potential of the obtained compounds by molecular modeling method.
Materials and methods. 4-Phenyl-5-(((5-phenylamino-1,3,4-thiadiazole-2-yl)thio)methyl)-1,2,4-triazole-3-thiol, which was synthesized by the classical method described in earlier works, was used as a key intermediate. The reaction of the corresponding thiol with sodium monochloroacetate in aqueous medium and subsequent acidification with ethanoic acid gave the target acid.
Inorganic salts of 2-((4-phenyl-5-(((5-phenylamino-1,3,4-thiadiazole-2-yl)thio)-methyl)-1,2,4-triazole-3-yl)thio)ethanoic acid was synthesized by the reaction of the acid with sodium hydroxide, potassium hydroxide, magnesium oxide, calcium carbonate or zinc sulfate in an aqueous medium. For analysis, the salts obtained were purified by crystallization from methanol.
Organic salts of 2-((4-phenyl-5-(((5-phenylamino-1,3,4-thiadiazole-2-yl)thio)-methyl)-1,2,4-triazole-3-yl)thio)ethanoic acid was obtained by the interaction of the corresponding acid with organic bases (ammonia, diethylamine, diethylmonoethanolamine, morpholine, piperidine) in propan-2-ol followed by evaporation of the solvent. For analysis, the synthesized substances were purified by crystallization from a mixture of water – propan-2-ol (1: 1).
Results. During the work, the method of obtaining 2-((4-phenyl-5-(((5-phenylamino-1,3,4-thiadiazole-2-yl)thio)methyl)-1,2,4-triazole-3-yl)thio)ethanoic acids was optimized. The role of the reaction medium at this stage was played by water. The conditions of the synthesis of organic and inorganic salts of the specified acid, their structure, and physical-chemical properties were established. The biological potential was preliminarily assessed with molecular docking.
Conclusions. As a result of synthetic studies, 11 new, previously undescribed compounds were obtained. The structure, composition and individuality of the synthesized substances was confirmed by a set of the latest physical-chemical methods of analysis.
References
Hotsulia, А. S., & Fedotov, S. O. (2019). Synthesis and properties of some S-derivatives of 4-phenyl-5-((5-phenylamino-1,3,4-thiadiazole-2-ylthio)methyl)-1,2,4-triazole-3-thione. Current issues in pharmacy and medicine: science and practice, 12(3), 245-249. https://doi.org/10.14739/2409-2932.2019.3.184170
Hotsulia, А. S., & Fedotov, S. O. (2020). Synthesis and properties of 5-(((5-amino-1,3,4-thiadiazole-2-yl)thio)methyl)-4-phenyl-1,2,4-triazole-3-thione and its some S-derivatives. Current issues in pharmacy and medicine: science and practice, 13(2), 182-186. https://doi.org/10.14739/2409-2932.2020.2.207062
Xie, W., Zhang, J., Ma, X., Yang, W., Zhou, Y., Tang, X., Zou, Y., Li, H., He, J., Xie, S., Zhao, Y., & Liu, F. (2015). Synthesis and biological evaluation of kojic acid derivatives containing 1,2,4-triazole as potent tyrosinase inhibitors. Chemical Biology and Drug Design, 86(5), 1087-1092. https://doi.org/10.1111/cbdd.12577
Gotsulya, A. S. (2017). Synthesis, structure and properties of N-R-amides and hydrazides of 2-[4-R-5-(theophylline-7ʹ-yl)-1,2,4-triazole-3-ylthio]acetic acid. Current issues in pharmacy and medicine: science and practice, 10(3), 254-258. https://doi.org/10.14739/2409-2932.2017.3.112748
Gotsulya, A. S. (2016). Synthesis and investigation of the physical-chemical properties of 2-(5-((theophylline-7’-yl)methyl)-4-methyl-4H-1,2,4-triazole-3-ylthio)acetic acid salts. Current issues in pharmacy and medicine: science and practice, (3), 4-7. https://doi.org/10.14739/2409-2932.2016.3.77832
Saidov, N. B., Kadamov, I. M., Georgiyants, V. A., & Taran, A. V. (2014). Planning, Synthesis, and Pharmacological Activity of Alkyl Derivatives of 3-Mercapto-4-Phenyl-5-Arylaminomethyl-1,2,4-Triazole-(4H). Pharmaceutical Chemistry Journal, 47(11), 581-585. https://doi.org/10.1007/s11094-014-1011-0
Singh, R., Kashaw, S., Mishra, V., Mishra, M., Rajoriya, V., & Kashaw, V. (2018). Design and synthesis of new bioactive 1,2,4-triazoles, potential antitubercular and antimicrobial agents. Indian journal of pharmaceutical sciences, 80(1), 36-45. https://doi.org/10.4172/pharmaceutical-sciences.1000328
Zhang, J., Wang, X., Yang, J., Guo, L., Wang, X., Song, B., Dong, W., & Wang, W. (2020). Novel diosgenin derivatives containing 1,3,4-oxadiazole/thiadiazole moieties as potential antitumor agents: Design, synthesis and cytotoxic evaluation. European journal of medicinal chemistry, 186, 111897. https://doi.org/10.1016/j.ejmech.2019.111897
Madhu Sekhar, M., Nagarjuna, U., Padmavathi, V., Padmaja, A., Reddy, N. V., & Vijaya, T. (2018). Synthesis and antimicrobial activity of pyrimidinyl 1,3,4-oxadiazoles, 1,3,4-thiadiazoles and 1,2,4-triazoles. European journal of medicinal chemistry, 145, 1-10. https://doi.org/10.1016/j.ejmech.2017.12.067
Keserü, G. M., & Makara, G. M. (2009). The influence of lead discovery strategies on the properties of drug candidates. Nature reviews. Drug discovery, 8(3), 203-212. https://doi.org/10.1038/nrd2796
Landry, Y., & Gies, J. P. (2008). Drugs and their molecular targets: an updated overview. Fundamental & Clinical Pharmacology, 22(1), 1-18. https://doi.org/10.1111/j.1472-8206.2007.00548.x
Biovia. (2019). Discovery Studio Visualizer, v 19.1.0.18287 [Software]. http://www. 3dsbiovia.com/
Sharma, V., Bhatia, P., Alam, O., Javed Naim, M., Nawaz, F., Ahmad Sheikh, A., & Jha, M. (2019). Recent advancement in the discovery and development of COX-2 inhibitors: Insight into biological activities and SAR studies (2008-2019). Bioorganic chemistry, 89, 103007. https://doi.org/10.1016/j.bioorg.2019.103007
Jacob, P. J., Manju, S. L., Ethiraj, K. R., & Elias, G. (2018). Safer anti-inflammatory therapy through dual COX-2/5-LOX inhibitors: A structure-based approach. European Journal of Pharmaceutical Sciences, 121, 356-381. https://doi.org/10.1016/j.ejps.2018.06.003
Downloads
How to Cite
Issue
Section
License
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access)
