Study of modern synthesis methods of 1,2,4-triazole derivatives, their reactivity, and pharmacological efficacy (Literature review)

Derivatives of 1,2,4-triazole are of significant interest in pharmaceutical and medicinal chemistry due to their broad spectrum of biological activity, including antimicrobial, antitumor, anti-inflammatory, and antifungal effects. Despite the availability of numerous known synthesis methods for these compounds, the ongoing search for new, more efficient, selective, and environmentally friendly approaches remains relevant. In addition, the study of the reactivity of 1,2,4-triazole derivatives opens up opportunities for the creation of new pharmacologically active molecules with targeted properties. Given the increasing demand for innovative pharmaceuticals, the systematization of current synthetic methods, analysis of the chemical behavior of triazoles, and assessment of their pharmacological effectiveness constitute an important area of research that contributes to the further development of medicinal chemistry. The aim of this work is to analyze modern methods for the synthesis of 1,2,4-triazole derivatives, evaluate their reactivity and pharmacological efficacy based on literature data, and identify prospects for the development of new medicinal agents. The study uses bibliosemantic analysis, generalization, comparison, and systematization of scientific sources. An analytical method was applied to assess synthetic approaches, including cycloaddition, S-alkylation, hydrazinolysis, oxidation, and the introduction of heterocyclic fragments. The systematization of data allowed for the evaluation of the biological activity of the compounds based on the results of in silico, in vitro, and in vivo studies. Based on the literature review, the following synthetic methods for 1,2,4-triazole derivatives were identified: cycloaddition, S-alkylation, hydrazinolysis, oxidation, and condensation, which enable the formation of compounds with various functional groups and heterocycles (pyrazole, triazine, piperazine). The application of modern approaches, such as microwave-assisted synthesis and Boc-protection, improves yields and product purity, offering flexibility in the design of new molecules. Electron-donating groups (e.g., amino, phenyl) enhance the reactivity of 1,2,4-triazoles in nucleophilic substitution sand condensations, while methyl or ethyl substituents may reduce it. Oxidation of sulfur to a hexavalent state yields sulfonyl compounds with enhanced biological activity. Scientific publications demonstrate that 1,2,4-triazole derivatives exhibit antibacterial, antifungal, anticancer, antioxidant, anti-inflammatory, anthelmintic, and stress-protective activities. Particularly promising are compounds that show low toxicity and cytotoxic effects against MCF-7, A-549, HeLa, and colon cancer cell lines, comparable to standard drugs.