The aim of the article is to predict the potential pharmacological activity of N-aryl-tetrahydro-5H-[1,2,4]triazolo-[4,3-a]azepin-3-ylmethyl)-amines and to establish a correlation relationship between the probability of biological activity and quantum chemical parameters of molecules.

Materials and methods. The calculation of quantum chemical parameters of molecules was performed using the ChemOffice software. Prediction of bioavailability and pharmacokinetic parameters was performed using the SwissADME online resource. Prediction of probable target proteins was performed using the online resource SuperPred. Molecular docking was performed using Webina 1.0.5, visualization and analysis of interactions were performed using Discovery Studio Visualizer. Microsoft Excel was used to perform correlation and regression analyses on the coordinates “binding affinity – quantum chemical descriptors.”

Results. The molecules of the studied triazoloazepine derivatives have electrophilic properties, as indicated by the energy values of the lower vacant molecular orbital. They contain several adsorption reaction centers, in particular, positively charged amine nitrogen atom and nitrogen atom common to the triazole and azepine cycles, as well as negatively charged nitrogen atoms of the triazole cycle. According to calculations, high bioavailability and low risks of hepatotoxicity and neurotoxicity are expected, meeting the requirements for potential drugs. An assessment of the compliance of triazoloazepine derivative molecules with the physicochemical parameters of bioavailability was carried out using radar diagrams. Correlation relationships were found between the probability of binding to Cathepsin D and Glutathione S-transferase Pi proteins and the quantum chemical parameters of the molecules. Good affinity was established for binding to proteins of the Carbonic anhydrase (VII, XII), Monoamine oxidase A and B, and Progesterone receptor. Binding occurs mainly with the participation of the electron density of cyclic fragments of molecules in the formation of π-alkyl, π-cation, π-π, π-σ, and stacking bonds. The interaction between triazoloazepine derivatives and potential target proteins occurs mainly with the participation of the electron density of cyclic fragments of molecules.

Conclusions. N-aryl-N-(6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[4,3-a]azepin-3-ylmethyl)-amines derivatives were found to have a high probability of binding to several potential target proteins. The formation of enzyme-ligand complexes may occur mainly with the participation of the electron density of cyclic fragments of molecules. The results obtained are important for further study of new triazoloazepine derivatives as perspective drug substances.