SYNTHETIC AND BIOLOGICAL ASPECTS OF STUDYING THE PROPERTIES OF 1,2,4-TRIAZOLE DERIVATIVES

1,2,4-triazoles belong to a well-known сlass of heterocyclic compounds that are of both theoretical and practical interest. This class has been known for about 100 years, and in recent decades 1,2,4-triazoles have become one of the most attractive objects of research in the chemistry of heterocyclic compounds due to their unique properties. Recently, a considerable number of innovative synthesis methods have been developed and interesting modification of chemical variations has been proposed, for example, a three-component reaction of aryldiazonium salts with fluorinated diazoreagents and nitriles, or a combination of a fragment of 1,2,4-triazole with coumarins or naphthalene-substituted compounds in one combined molecule, and so on. As a result, scientists have obtained new derivatives of 1,2,4-triazoles with a certain number of structural features that contribute to the production of promising substances with antimicrobial, antifungal, antitubercular, antioxidant, antitumor effects, etc. These derivatives are used not only in the medical and veterinary sphere, but also in the agricultural and industrial sectors. They have found their application as dyes, corrosion inhibitors, photosensitizers, fungicides, plant growth regulators, etc. The aim of our work was to analyze and summarize the known literature data on new synthetic approaches to the production of new derivatives of 1,2,4-triazole and systematize information related to the biological properties of these compounds.


Introduction
Triazoles are part of a five-membered heterocycle family, scientific interest is constantly growing to it (Parchenko V.V., 2014). This is primarily due to the wide range of applications of derivatives of this system in the pharmaceutical, agricultural and technical industries (Bigdan O. A., 2017: 135-140). 1,2,4-Triazole is a system with a symmetric arrangement of three nitrogen atoms and two carbon atoms, which give unique properties to these derivatives (Parchenko V. V., 2011: 49-53). In addition, 1,2,4-triazoles are a key building block of a large number of molecular structures with antibacterial, antifungal, anti-tuberculosis, antioxidant, antitumor, analgesic, anti-inflammatory activity, etc. (Borisenko N.N., 2019: 1-5). The possibility of additional introduction of various substituents into the "framework" of 1,2,4-triazole is crucial in modeling new "libraries" of promising compounds (Bigdan O.A., 2016: 90-97). Therefore, the strategy of "building" new substituted 1,2,4-triazole is popular among scientists due to the additional introduction of various pharamcoforic residues. The wide range of biological and pharmacological properties of 1,2,4-triazole encourages scientists in many countries of the world to develop new synthetic approaches for the targeted production of new derivatives of 1,2,4-triazole.
The aim of our work was to analyze and summarize the known literature data on new synthetic approaches to the production of 1,2,4-triazole derivatives and systematize information related to the biological properties of these compounds.

Review of potential prospects for 1,2,4-triazoles
An original method for the synthesis of both symmetric and unbalanced 3,4,5-triaryl-1,2,4-triazoles using B(C6F5)3 as a catalyst is proposed by a team of scientists (Guru M. M., 2019: 7964-7974). The authors proved that B(C6F5)3 performs a dual role, firstly, it activates the corresponding hydrazone for nucleophilic attack, and secondly, it initiates the formation of a frustrated Lewis pair for dehydrogenation. This method is economical, and without the presence of oxidizing agents, it can become a potential platform for chemical conversion catalyzed by the main group without the use of a transitive metal.
Isocyanoacetates are universal substrates for the synthesis of heterocyclic compounds. The authors investigated the reaction of decarboxylative cancellation of 2-aryl-2isocyanoacetates with aryldiazonium salts (Tian Y. T., 2021: 227-233). This method makes it possible to produce a large number of new molecules in a number of 1,3-diaryl-1,2,4-triazoles, including binaphthalene, potential drug compounds, and synthetic intermediates of drug-like molecules. The three-component reaction of aryldiazonium salts with fluorinated diazoreagents and nitriles deserves attention. (Peng X., 2020: 4432-4437). The method makes it possible to expand the spectrum of difluoromethylated N1-aryl-1,2,4-triazoles, most of which show similarity to drug molecules.
The development of powerful urease inhibitors can be considered as a promising area of scientific research. A team of scientists has developed structurally diverse compounds containing coumarin and thiazolo-1,2,4-triazole in one combined molecule (Khan, I., 2020: 345-354). The combination of fragments of 1,2,4-triazole and naphthalene-substituted compounds in one molecule leads to the formation of substances with high antitumor activity (Luo L., 2021: 113039). Some compounds have cytotoxicity in vitro, stopping the cell cycle and inducing apoptosis in MDA-MB-231 cells. in addition, the compounds have been found to inhibit the growth of 4T1 breast tumors. Another team of scientists described in detail the production of new spirocyclic and chiral triazolopiperazines (Lorthioir O., 2020: 152600). The authors have developed a practical, fast and reliable synthetic pathway for the synthesis of these derivatives, which allows you to control Regio -and stereochemistry. The reaction conditions are quite mild. Available amino acids and amidins can be used as starting components. The resulting 5,6,7,8-tetrahydro- [1,2,4]triazolo [1,5-a]pyrazines are attractive molecules for finding potential drugs among them. Heterocyclic nitrogen compounds are important structural subunits that are widely found in bioactive natural products, pharmaceuticals, agrochemicals, and the like. Recently, attention has been paid to arendiazonium salts, which are a source of nitrogen -the main component in the synthesis of nitrogen-containing heterocyclic compounds (Liu J., 2020: 4876-489). According to the authors, the direction of combining 1,2,4-triazole and the Quinoline "core" in one molecule due to condensation of 5-(4-chlorphenoxymethyl)-2,4-dihydro-1,2,4-triazole-3-thiones and 5-(pyridine-3-yl)-4H-1,2,4-triazole-3-thiols with substituted 2-chlorquinoline-3-carbaldehydes is promising (D'Souza V. T., 2021: 129503).
The strategy of donor-acceptor diazoactivation is a promising area of synthetic testing. The authors convincingly proved the possibility of constructing molecules by condensation using diazonium salts, and also found that the intermediate product undergoes  (Aly A. A., 2017: 2375-2379). The reaction takes place in the presence of equimolar amounts of phthaloyl chloride and N-arylbenzamidrazone in the presence of two triethylamine (Et3N) equivalents. The high reactivity of amidins makes them valuable intermediates in the synthesis of heterocyclic compounds, organocatalysts, and metal complexes. The authors studied in detail the reactivity of amidins in the synthesis of 1,2,4-triazole-containing compounds (Aly A. A., 2018: 85-138). Another team of scientists has developed a lightweight and versatile catalytic system that includes a copper catalyst, K3PO4, and an oxidizer to ensure efficient synthesis of 2,4,6-triazines, 2,6-dizaminated 1,3,5-triazines, and 1,3-dizaminated 1,2,4-triazines (Huang H., 2015: 2894-2897).
Derivatization of the triazole ring is based on the phenomenon of bioisosterism, in which the oxygen of the oxadiazole core is replaced by a nitrogen analog of triazole. This review provides a brief overview of the medical chemistry of the triazole system and highlights some examples of recent drugs containing this part in the current literature. Triazole is a unique component that is responsible for a variety of biological activities. This article highlights the research work of many researchers, which is described in the literature on various pharmacological activities for synthesized triazole compounds. This review provides comprehensive information about triazole analogues, powerful compounds that have been reported for certain pharmacological activity, as well as the method involved in the evaluation process (Kumar R, 2013(Kumar R, : 1844(Kumar R, -1869. So far, it has been observed that modifications of the triazole part lead to the formation of compounds with valuable biological activity. It will be interesting to note that these modifications can be used as powerful therapeutic agents in the future. 1,2,4-Тriazoles have attracted considerable attention in the field of Medicine and agrochemical research, as well as in materials science due to their unique structure and properties. 1,2,4-triazole and its derivatives belong to the class of exclusively active compounds with many pharmacological properties. Some triazole derivatives are also known to exhibit antitumor activity. 1,2,4-riazoles are of great importance, as they have also been studied for their depressive, pesticide, antimycobacterial, hypoglycemic, diuretic, insecticidal and herbicidal effects on the central nervous system. Sulfonamide preparations (sulfonamide preparations) were the first antimicrobials to pave the way for the antibiotic revolution in medicine. From a structural point of view, sulfonamides are interesting because of their tendency to form different hydrogen bond systems in the solid state by introducing various hydrogen bond donors and acceptors as substituents into simple sulfonamide molecules. In addition, sulfur-containing heterocycles represent an important group of sulfur compounds that are promising for practical applications. Among these heterocycles, mercapto -and Thion-substituted 1,2,4-triazole ring systems have been well studied, and so far the diverse biological activity of a large number of their derivatives has been reported. It has been reliably established that various triazole derivatives have a wide range of pharmacological properties. 1,2,4 is a triazole fragment present in various natural products and compound synthesis. This part has attracted the attention of both chemists and biologists. Compounds containing different heterocyclic fragments will be tested for antimicrobial activity against different strains of pathogens. Similarly, some of the compounds will also be tested for anti-inflammatory and analgesic effects. Many therapeutically important medications available, such as ketoconazole, itraconazole, voriconazole, and fluconazole, contain this heterocyclic nucleus. Taking into account the above facts and continuing interest in heterocycles containing the 1,2,4-triazole fragment, identify as a new molecule that may be important in the development of new, powerful, selective and less toxic antimicrobial agents. This combination is seen as an attempt to investigate the effect of structure variation on predicted biological activity, hoping to add some synergistic biological significance to the target molecules.