Creation, study of physical and chemical properties of 2-((4-R-5-phenethyl-4H-1,2,4-triazole-3-yl)thio)ethanоic(propanоic, benzoic)acids and salts of 2-((4-R-5-phenethyl-4H-1,2,4-triazole-3-yl)thio)ethanoic acid
DOI:
https://doi.org/10.14739/2409-2932.2019.2.170973Keywords:
1, 2, 4-triazole, synthesis, physical and chemical propertiesAbstract
C
A large number of native and foreign scientists are involved in the synthesis of 3-thio-1,2,4-triazole. Today, a huge number of drugs based on 3-thio-1,2,4-triazole has been created, including itraconazole, fluconazole, voriconazole, letrozole, thiotriazoles. It was revealed that the largest number of drugs based on the above-mentioned heterocyclic system is based on the salts of 1,2,4-triazole, therefore, the synthesis of acids and salts of 1,2,4-triazole is relevant.
The purpose of the work is targeted search and creation of new biologically active compounds, derivatives of 5-phenethyl-4-R-4H-1,2,4-triazole-3-thioles, which exhibit low toxicity, as well as establishment of their physical-chemical properties.
Materials and methods. The melting point has been determined by the capillary method on the PTP device. The elemental composition of the compounds has been determined on the elemental analyzer Elementar Vario L cube (Elementar Vario, Germany). The IR spectra of the synthesized compounds have been recorded on a Specord 200 (Specord, Germany) spectrophotometer in the range of 4000–500 cm-1. The 1H NMR spectra have been recorded on a Varian VXR-300 (Varian, USA) nuclear magnetic resonance spectrophotometer and decoded using the ADVASP 143 computer program. Chromato-mass spectral studies have been performed on Agilent 1260 Infinity HPLC (Agilent Technologies, USA) liquid chromatograph equipped with an Agilent 6120 mass spectrometer.
Results. Two methods for the creation of 2-((4-R-5-phenethyl-4H-1,2,4-triazole-3-yl)thio)ethanoic(propanoic, benzoic)acids have been proposed. At the next stage, salts of 2-((4-R-5-phenethyl-4H-1,2,4-triazole-3-yl)thio)ethanoic acids were obtained by the interaction of 2-((4-R-5-phenethyl-4H-1,2,4-triazole-3-yl)thio)ethanoic acids with salts of Cu2+, K+ and Na+ in an alkaline medium or with methylamine (ethylamine, butylamine) in an alcohol medium. The structure of all synthesized compounds was confirmed by the complex use of elemental analysis, IR spectrophotometry and 1H NMR spectrometry, and their individuality was proved chromatographically.
Conclusions. During the synthetic studies 12 new, not previously described compounds were received. Preparative synthesis procedures for 2-((4-R-5-phenethyl-4H-1,2,4-triazole-3-yl)thio)ethanoic(propanoic, benzoic)acids and salts of 2-((4-R-5-phenethyl-4H-1,2,4-triazole-3-yl)thio)ethanoic acids were created. The structure of the synthesized compounds was confirmed using a complex of modern research methods.
References
Kaplaushenko, A. H., Sameliuk, Yu. H., & Kucheriavyi, Yu. M. (2016) Praktychne znachennia ta zastosuvannia pokhidnykh 1,2,4-triazolu [Practical value and application of derivatives of 1,2,4-triazole]. Zaporizhzhia. [in Ukrainian].
Hulina, Yu. S., & Kaplaushenko, А. G. (2018) Synthesis, physical and chemical properties of 5-((1Н-tetrazole-1-yl)methyl)-4-R-4Н-1,2,4-triazole-3-thiols and their chemical transformations. Biopharmaceutical jornal, 1(10), 26–30.
Rud, A. M., Kaplaushenko, A. G., & Yurchenko, I. O. (2018) Synthesis, physical and chemical properties of 2-((5-(hydroxy(phenyl)methyl)-4R-4H-1,2,4-triazole-3-yl)thio)acetic acids and its salts. Zaporozhye medical journal, 20, 1(106), 105–109. doi: 10.14739/2310-1210.2018.1.122126
Wu, J.-W., Yin, L., Liu, Y.-Q., Zhang, H., Xie, Y. F., Wang, R. L., & Zhao, G. L. (2019) Synthesis, biological evaluation and 3D-QSAR studies of 1,2,4-triazole-5-substituted carboxylic acid bioisosteres as uric acid transporter 1 (URAT1) inhibitors for the treatment of hyperuricemia associated with gout. Bioorganic and Medicinal Chemistry Letters, 29(3), 383–388. doi: 10.1016/j.bmcl.2018.12.036
Hassan, A. A., Mohamed, N. K., Aly, A. A., Bräse, S., & Nieger, M. (2019) Eschenmoser-Coupling Reaction Furnishes Diazenyl-1,2,4-triazole-5(4H)-thione Derivatives. ChemistrySelect, 4(2), 465–468. doi: 10.1002/slct.201802870
Moreno-Fuquen, R., Arango-Daraviña, K., Becerra, D., Castillo, J. C., Kennedy, A. R., & Macías, M. A. (2019) Catalyst- and solvent-free synthesis of 2-fluoro-N-(3-methylsulfanyl-1H-1,2,4-triazol-5-yl)benzamide through a microwave-assisted fries rearrangement: X-ray structural and theoretical studies. Acta Crystallographica Section C: Structural Chemistry, 75(Pt 3), 359–371. doi: 10.1107/S2053229619002572
Tang, Y., Yu, F., Huang L., & Hu, Z. (2019) The changes of antifungal susceptibilities caused by the phenotypic switching of Candida species in 229 patients with vulvovaginal candidiasis. Journal of Clinical Laboratory Analysis, 33(1), e22644. doi: 10.1002/jcla.22644
Lindberg, E., Hammarström, H., Ataollahy, N., & Kondori, N. (2019) Species distribution and antifungal drug susceptibilities of yeasts isolated from the blood samples of patients with candidemia. Scientific Reports, 9(1), 3838–3850. doi: 10.1038/s41598-019-40280-8
Gautier-Veyret, E., Truffot, A., Bailly, S., Fonrose, X., Thiebaut-Bertrand, A., Tonini, J., et al. (2019) Inflammation is a potential risk factor of voriconazole overdose in hematological patients. Fundamental and Clinical Pharmacology, 33(2), 232–238. doi: 10.1111/fcp.12422
Johnston, S., Puhalla, S., Wheatley, D., Ring, A., Barry, P., Holcombe, C., et al. (2019) Randomized phase II study evaluating palbociclib in addition to letrozole as neoadjuvant therapy in estrogen receptor–positive early breast cancer: Pallet trial. Journal of Clinical Oncology, 37(3), 178–189. doi: 10.1200/JCO.18.01624
Mitwally, M. F., & Casper, R. F. (2001) Use of an aromatase inhibitor for induction of ovulation in patients with an inadequate response to clomiphene citrate. Fertil Steril, 75(2), 305–309. doi: https://doi.org/10.1016/S0015-0282(00)01705-2
Rud, A. M., Kaplaushenko, A. G., Pruglo, Ye. S., & Frolova, Yu. S. (2018) Vstanovlennia pokaznykiv diuretychnoi dii (3-tio-4-R-4N-1,2,4-triazol-5-il)(fenil)metanoliv ta yikh pokhidnykh [Establishment of diuretic activity indicators for (3-thio-4-R-4-H-1,2,4-triazole-5-yl)(phenyl)methanols and their derivatives]. Current issues in pharmacy and medicine: science and practice, 2, 215–219. [in Ukrainian]. doi: 10.14739/2409-2932.2018.2.134004
Hulina, Yu. S., & Kaplaushenko, A. G. (2016) Syntez i fizyko-khimichni vlastyvosti 2-(5-(1H-tetrazol-1-ilmetyl)-4-R-4H-1,2,4-triazol-3-iltio)-atsetatnykh(propanovykh), 2-, 4-(5-(1H-tetrazol-1-ilmetyl)-4-fenil-4H-1,2,4-triazol-3-iltiometyl)-benzoinykh kyslot ta yikh solei [Synthesis and physical-chemical properties of 2-(5-(1Н-tetrazol-1-ylmethyl)-4-R-4Н-1,2,4-triazol-3-yltio)-acetic (propanoic), 2-, 4-(5-(1Н-tetrazol-1- ylmethyl)-4-phenyl-4Н-1,2,4-triazol-3- yltiometil)-benzoic acids and their salts]. Current issues in pharmacy and medicine: science and practice, 2, 32–37. [in Ukrainian]. doi: 10.14739/2409-2932.2016.2.71115
(2001) Derzhavna Farmakopeia Ukrainy [The State Pharmacopoeia of Ukraine]. Kharkiv: RІREG. [in Ukrainian].
(2004) Derzhavna Farmakopeia Ukrainy [The State Pharmacopoeia of Ukraine]. Kharkiv: RІREG. [in Ukrainian].
Kazicyna, L. A., & Kupletskaya, N. B. (1979) Primenenie UF-, IK-, YaMR- i MASS-spektroskopii v organicheskoj khimii [Application of UV, IR, NMR and mass spectroscopy in Organic Chemistry]. Moscow: Izd-vo Mosk. un-ta. [in Russian].
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)
