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

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