Synthesis of new potential biological active substances among 3-mercapto-4-amino-5-benzyl-1,2,4-triazol-4H derivatives

  • N. B. Saidov Tadzhik National University, Dushanbe
  • V. A. Georgiyants National University of Pharmacy, Kharkіv
  • N. V. Garnaya National University of Pharmacy, Kharkіv
Keywords: 3-mercapto-4-amino-5-benzyl-1,2,4-triazole, derivatives, alkylation, synthesis, Paal–Knorr reaction, activity prediction

Abstract

Conventional approaches to the formation of 1,2,4-triazole ring allow to introduce different substituents into the heterocyclic ring during the synthesis of key intermediates stage. In continuation of previous studies the synthesis of 3-mercapto-4-amino-5-benzyl-1,2,4-triazole-4H derivatives is described.

The aim of investigation was synthesis of a series of new derivatives of 3-mercapto-4-amino-5-benzyl-1,2,4-triazole, proving their structure by physico-chemical methods and planning of pharmacological screening using PASS.

Phenylacetic acid ethyl ester has been used for the synthesis as starting substance. It was subjected to hydrazinolysis to receive an appropriate hydrazide. In the next stage substance obtained was processed with hydrogen disulfide and appropriate potassium ditiokarbaminat has been received, which by reaction with an excess of hydrazine hydrate has been cyclised into a target 3-mercapto-4-amino-5-benzyl-1,2,4-triazol-4H. The first stage of chemical transformation reactions of key intermediate was its alkylation with chloroacetanilides under alkaline catalysis. By Paal–Knorr reaction the amino group in the synthesized alkylthio-4-amino-5-benzyl-1,2,4-triazole-4H was modified into pyrrole ring by the action of 2,5-dimethoxytetrahydrofuran in acetic acid medium.

The structure of the compounds synthesized has been proved by 1H NMR spectroscopy. The successful alkylation of mercapto group indicates the disappearance of its proton signal at the spectra and appearance of the acetanilide residues protons signals. Modification of the amino derivatives into corresponding pyrrolyl substituted has been accompanied by the appearance of the triplet signals of magnet equivalent methyne protons of the pyrrole ring (protons at positions 3.4) at 6.30 ppm. The signals of the second pyrrole protons pair overlap with other aromatic protons signals.

For the planning of pharmacological screening previous prognosis of the potential pharmacological activity spectrum has been carried out using software PASS. The prognosis showed that for all pyrrolyl substituted substances predominant in the spectrum of action was the influence on the central nervous system, and the probability of the activity of their synthetic precursors mainly limited to moderate antioxidant properties.

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Published
2018-09-04
How to Cite
Saidov, N. B., Georgiyants, V. A., & Garnaya, N. V. (2018). Synthesis of new potential biological active substances among 3-mercapto-4-amino-5-benzyl-1,2,4-triazol-4H derivatives. Farmatsevtychnyi Zhurnal, (3), 52-57. https://doi.org/10.32352/0367-3057.3.15.01
Section
Synthesis and analysis of biologically active compounds