Synthesis, physicochemical properties and antigypoxic activity of some S-derivatives of 4-alkyl-5-(((3-(pyridin-4-yl)-1H-1,2,4-triazol-5-yl)thio)methyl)-4H-1,2,4-triazole-3-thiol

Keywords: synthesis, 1,2,4-triazole, antihypoxic activity


Hypoxia is a discrepancy between the required energy of the cell in the mitochondrial oxidative phosphorylation system. The immediate cause of the deficiency is a decrease in the oxygen concentration in the mitochondria. Today there is a huge demand for the development of new anti-hypoxic drugs. t is known that 1,2,4-triazole compounds can have antimicrobial, anti-inflammatory, anti-hypoxic effects. Modification of the 1,2,4-triazole nucleus is a productive way to create original active molecules with a non-planar structure, for their binding to bio-target substrates. Derivatives of bis-1,2,4-triazoles may become potential compounds with anti-hypoxic action.

The aim of our work was to synthesize new S-derivatives of 4-alkyl-5-(((3-(pyridine-4-yl)-1Н-1,2,4-triazole-5-yl)thio)methyl)-4Н-1,2,4-triazole-3-thiols, to investigate their physicochemical parameters using modern complex physicochemical research methods and to conduct primary pharmacological screening for anti-hypoxic activity in models of acute hypoxia with hypertension.

The object of the study was the S-derivatives of 4-alkyl-5-(((3-(pyridine-4-yl)-1Н-1,2,4-triazole-5-yl)thio)methyl)-4Н-1,2,4-triazole-3-thiols. The structure of the synthesized compounds was confirmed by elemental analysis (CHNS), 1H NMR, the individuality of the molecules was proved by chromatographic mass spectral analysis. 1H NMR signals for substances are consistent with the proposed structure. The study of the anti-hypoxic activity of the got compounds of the series of S-substituted bis-1,2,4-triazoles was carried out on models of acute hypoxia with hypertension, where Mexidol (5%) 200 mg/kg as a reference drug.

New S-derivatives of 4-methyl-5-(((3-(pyridine-4-yl)-1Н-1,2,4-triazole-5-yl)thio)methyl)-4Н-1,2,4-triazole-3-thiols (I a) and 4-ethyl-5-(((3-(pyridine-4-yl)-1Н-1,2,4-triazole-5-yl)thio)methyl)-4Н-1,2,4-triazole-3-thiols (I b) with acyl-aryl, acyl-alkyl and alkyl substituents. We studied their spectral parameters, physicochemical properties in the conditions of GC/MS, elemental analysis, 1H NMR spectroscopy. According to the results of biological studies on the anti-hypoxic effect, it was found that 1-((4-ethyl-5-(((3-(pyridine-4-yl)-1H-1,2,4-triazole-5-yl)thio)methyl)-4H-1,2,4-triazole-3-yl)thio)propane-2-one is a compound that exceeds the anti-hypoxic activity of Mexidol and increases the lifespan of rats by 1.0% relative to the reference drug.


Seifulla R. D. Sportyvnaia farmakolohyia: spravochnyk. – M.: Moskovskaia pravda, 2001. – 101 s.

Odyntsova V. M., Knysh Ye. H., Panasenko O. I. Syntez, fizyko-khimichni vlastyvosti, antyhipoksychna aktyvnist deiakykh 5-|((5-(adamantan-1-il)-4-R-4H-1,2,4-triazol-3-il)tio)metyl|-N-R1-1,3,4-tiadiazol-2-aminiv ta 5-|((5-(adamantan-1-il)-4-R-4H-1,2,4-triazol-3-il)tio)metyl|-4-R1-4H-1,2,4-triazol-3-tioliv // Aktualni pytannia farmatsevtychnoi i medychnoi nauky ta praktyky. ‒ 2018. ‒ T. 11, № 1. ‒ S. 17‒22.

Odyntsova V. M., Pruglo Ye. S. Synthesis, physical-chemical properties and the study of anti-hypoxemic activity of 5-(adamantane-1-yl)-4-R-1,2,4-triazole-3-thion alkylderivative // Zaporozh. med. zhurn. ‒ 2015. ‒ № 2. – S. 93–96.

Suhak O. A., Panasenko O. I., Knysh Ye. H. Antyhipoksychna aktyvnist benzylidenhidrazydiv 4-R-5-(tiofen-2-ilmetyl)-1,2,4-triazol-3-il)tiootstovoi kysloty // Aktual. pytannia farmats. med. nauky ta praktyky. – 2017. – T. 10, № 2. – S. 147–151.

Gotsulya A. S. Synthesis and physical properties of esters of 2-[5-((theophylline-7-yl)methyl)-4-R-1,2,4-triazole-3-ylthio]acetic acid // Aktual. pytannia farmats. med. nauky ta praktyky. – 2017. – T. 10, № 2. – S. 124–128.

Pruhlo Ye. S. Antyoksydantna aktyvnist solei 2-(5-R-4-amino-1,2,4-triazol3-iltio)otstovykh kyslot // Aktual. pytannia farmats. мed. nauky ta praktyky. – 2017. – T. 10, № 3. – С. 25.

Borisenko N., Bushueva I., Parchenko V. et al. Anti-Inflammatory, Antiviral Veterinary Medicine with Immuno-Modulating Activity // Res. J. Pharmacy Technol. – 2019. – V. 12, N 11. – Р. 5255.

Metodychni vkazivky po doklinichnomu vyvchenniu likarskykh zasobiv / Pid red. A. V. Stefanova. – K., 2001. – 567 s.

Voronyna T. A. Antyoksydant meksydol. Osnovnыe neiropsykhotropnыe efekty y mekhanyzm deistvyia // Psykhofarmakolohyia y byolohycheskaia narkolohyia. – 2001. – № 1. – S. 2–12.

Shcherbyna R. Microwave-Assisted Synthesis Of Some New Derivatives of 4-substituted-3-(morpholinomethyl)-4h-1,2,4-triazole-5-thioles // Ankara Universitesi Eczacilik Fakultesi Dergisi. – 2019. – T. 43, № 3.– S. 220–229.

Safonov A. Derivatives of 3-(alkylthio)-5-(thiophen-2-ylmethyl)-4H-1,2,4-triazol-4-amines as increasing efficiency substances // Indonesian J. Pharmacy. – 2018. – V. 29, N 3. – P. 167.

How to Cite
Karpun, E. O., & Parchenko, V. V. (2020). Synthesis, physicochemical properties and antigypoxic activity of some S-derivatives of 4-alkyl-5-(((3-(pyridin-4-yl)-1H-1,2,4-triazol-5-yl)thio)methyl)-4H-1,2,4-triazole-3-thiol . Farmatsevtychnyi Zhurnal, (6), 56-64.
Synthesis and analysis of biologically active compounds