Synthesis and investigation of the biological properties of alkyl, aryl, and heteryl 5-(2,2-dichloro-1-methylcyclopropyl)-4-phenyl-3-thio-4h-1,2,4-triazole

Topicality. The importance of the class of azaheterocycles compounds for the production of biologically active substances and drugs cannot be overestimated. This class of organic compounds is unique. This confirms the use of various derivatives of this system as effective medicines with antifungal, antiviral, anticancer and neuroleptic activity. These substances have also been used in agriculture and veterinary medicine.[2;4]

In this connection, the creation of new derivatives of azaheterocyclic structures for the purpose of the search for biologically active substances is endowed with all signs of urgency and has a practical significance[1;5].

The purpose of our work was to find promising biologically active substances in the range of alkyl-, aryl- and heteryl 5-(2,2-dichloro-1-methylcyclopropyl)-4-phenyl-3-thio-4H-1,2,4-triazole.

To achieve this goal, the following tasks were solved: to study the conditions, to propose preparative techniques, and to carry out a phased synthesis of alkyl, aryl, and heteryl derivatives of 5-(2,2-dichloro-1-methylcyclopropyl)-4-

phenyl-3-thio-4H-1,2,4-triazole, to prove the structure of the compounds obtained and to determine the possible and perspective directions of the biological activity research.

Materials and method. As the starting compound for the preparation of the target products, chloroform and n-butyl methacrylate were used, from which in the process of chemical conversion, an ester which was subsequently subjected to hydrazinolysis reactions of AN addition with phenylisothiocyanate and subsequent molecular cyclization was obtained. Further, the thiol produced was reacted with S-alkylation, acylation and heterylization (Fig.).

To confirm the structure of the resulting compounds and to prove the completeness of the chemical reactions, elemental analysis, 1H NMR spectroscopy and IR spectrophotometry were used.

The individuality of the synthesized substances is confirmed by chromatic mass spectrometry.

To determine the optimal direction of pharmacological screening, a prediction of the possible activity of synthesized substances was performed using the PASS On-line® service and molecular docking.

Results. A strategy for the formation of target reaction products with the use of basic pharmacophores and a direction for further modification of 5-(2,2-dichloro-1-methyl-cyclopropyl)-4-phenyl-3-thio-4H-1,2,4-triazole has been developed. The conducted pharmacological screening for diuretic activity allowed determining a compound with pronounced diuretic activity.

Conclusions. A universal method for the preparation of alkyl, aryl, and heteryl 5-(2,2-dichloro-1-methyl- cyclopropyl)-4-phenyl-3-thio-4H-1,2,4-triazole was developed. Among the synthesized substances, a compound that is promising in terms of further in-depth studies of diuretic activity is highlighted.



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Year: 2018
City: Shymkent
Category: Medicine