Synthesis and properties of S-alkyl 4-amino-5-(5-(3-fluorophenyl)-pyrazol-3-yl)-1,2,4-triazole-3-thiol derivatives

Abstract

An important direction of modern pharmaceutical science is the creation of promising biologically active compounds, which in the hands of scientists can be transformed into effective medicinal products. Heterocyclic compounds are the undisputed leader in solving this problem. A well-known fact and a well-founded approach to achieving the desired pharmacological effect is the combination of different heterocyclic fragments in the structure of one molecule. And here it makes sense to focus our attention on such heterocycles as pyrazole and 1,2,4-triazole. After all, a number of well-known medicines have already been invented on their basis. Thus, the construction of a chemical tandem with heterocyclic blocks of the specified nature is an actual and promising direction of scientific work. The aim of the work was to create a number of S-alkyl derivatives of 4-amino-5-(5-(3-fluorophenyl)pyrazol-3-yl)-1,2,4-triazole-3-thiol and study their properties, as well as preliminary selective establishment biological potential of these compounds. Materials and methods. The synthesis of the target products of chemical transformation was successfully implemented by the step-by-step use of well-known methods of organic synthesis. Thus, the first stage was successfully implemented with the help of available reagents, the role of which was performed by diethyl oxalate and 1-(3-fluorophenyl)ethan-1-one with the participation of sodium methylate. The next stage involved hydrazinolysis. Subsequently, the corresponding potassium xanthogenate was successfully synthesized, which was subsequently transformed under the action of hydrazine hydrate into the target 4-amino-5-(5-(3-fluorophenyl)pyrazol-3-yl)-1,2,4-triazole-3-thiol. The next stage was S-alkylation. The structure of all synthesized substances was determined with IR spectrophotometry, 1H NMR spectroscopy, and elemental analysis. The individuality of the compounds was confirmed by high-performance liquid chromatography-mass spectrometry. In silico studies were carried out with well-known software products, namely: AutoDock Vina, Biovia Discovery Studio, Hyper Chem 7.5, and Open Babel. Cyclooxygenase-2, lanosterol 14α-demethylase, and anaplastic lymphoma kinase were used as model enzymes. Results. The optimal conditions for the stepwise creation of S-alkyl derivatives of 4-amino-5-(5-(3-fluorophenyl)pyrazol-3-yl)-1,2,4-triazole-3-thiol were established and the preparation of the specified compounds was carried out. The use of molecular docking made it possible to determine the perspective of further research on anti-inflammatory, antifungal, and antitumor properties in a number of synthesized structures. Conclusions. S-alkyl derivatives of 4-amino-5-(5-(3-fluorophenyl)pyrazol-3-yl)-1,2,4-triazole-3-thiol are reasonably promising objects for the study of antifungal activity.