Synthesis, structure and properties of 7-((4-amino-5-thio-1,2,4-triazole-3-yl)methyl)-theophylline derivatives
Keywords:1, 2, 4-triazole, theophylline, physical-chemical properties, molecular docking
The combination of derivatives of 1,2,4-triazole and theophylline creates fertile soil for biologically active substances. The use of these heterocyclic systems allows the use of simple chemical modification methods and available reagents. This determines the relevance of the chosen direction of scientific research.
The aim of the work was to study synthesis methods and study the properties of heterocyclic systems containing theophylline and 1,2,4-triazole fragment in their structure, create a chemical variety that was interesting from a scientific point of view and was promising in the search for biologically active substances.
Materials and methods. Theophylline was used as the starting material. Using alkylation reactions, hydrazinolysis, interaction with a carbon disulfide followed by heterocyclization with an excess of hydrazine hydrate, 7-((4-amino-5-thio-1,2,4-triazole-3-yl)methyl)theophylline was obtained. The following stages of the chemical conversion included alkylation reactions with haloalkanes, the formation of azomethine compounds by reaction with aromatic aldehydes, and the reaction with aromatic carboxylic acid chlorides. The structure of the obtained compounds was confirmed by data of elemental analysis, 1H NMR spectroscopy and IR-spectrophotometry. The individuality of substances was established by using high performance liquid chromatography with diode-array and mass spectrometric detection.
Results. S-alkylderivatives of 7-((4-amino-5-thio-1,2,4-triazole-3-yl)methyl)-theophylline, Schiff bases and carboxamides were synthesized, their structure was proved, and physical properties were investigated.
The synthesized compounds have been subjected to the in silico molecular docking study against the kinases of anaplastic lymphoma by using the 2XP2 ligand, lanosterol 14-α-demethylase by using the 3LD6 ligand, cyclooxygenase-2 by using the ligand 4Z0L which were downloaded from the protein data bank (PDB).
Conclusions. Molecular docking has shown the ability of the synthesized compounds to influence the kinase activity of anaplastic lymphoma, cyclooxygenase-2 and lanosterol-14-α-demethylase.
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