Structural modification of the 1,2,4-triazole core as a strategy for the design of biologically active compounds (Literature Review)

The aim. The aim of this review article is to systematize and summarize current literature data on methods of chemical modification of 1,2,4-triazole derivatives, as well as to analyze the impact of structural transformations on their biological activity and pharmacological potential. Materials and methods. The analysis was based on scientific publications by domestic and international authors devoted to the synthesis, functionalization, and biological evaluation of 1,2,4-triazole derivatives. Data generalization was carried out using methods of systematic analysis, comparative assessment of synthetic approaches, and analysis of the results of in silico, in vitro, and in vivo studies (molecular docking, ADME analysis, SAR evaluation). Results. It has been shown that 1,2,4-triazole derivatives are characterized by high chemical lability and the ability to undergo modification at the sulfur atom, amino group, and nitrogen atoms of the heterocyclic core. Alkylation and acylation reactions, salt formation, hybridization with other pharmacophoric fragments, as well as the application of microwave-assisted synthesis enable the development of compounds with a wide spectrum of biological activity. Among the studied derivatives, compounds exhibiting antioxidant, antimicrobial, antitumor, anti-inflammatory, neuroprotective, and hypoglycemic activities have been identified. A correlation between the chemical structure of the compounds, the nature of substituents, and their pharmacological properties has been established. Conclusions. 1,2,4-Triazole derivatives represent a promising pharmacophoric platform for the development of new biologically active compounds. Further targeted investigation of their chemical modification pathways and structure–activity relationships offer broad opportunities for the design of potential therapeutic agents