This study investigates the ADME properties of newly synthesized derivatives of 3,5-bis(5-mercapto-4-R-4H-1,2,4-triazol-3-yl)phenols and their alkylated analogues.

Aim: to evaluate the effect of structural modifications, such as alkylation, chain elongation, and introduction of substituents, on absorption, distribution, metabolism, and excretion parameters, with an emphasis on drug-likeness and medicinal potential.

Materials and methods. Computational approaches using SwissADME tools were applied to predict key physicochemical and pharmacokinetic descriptors, including molecular weight, TPSA, lipophilicity (LogP), solubility, gastrointestinal absorption, P-glycoprotein substrate recognition, and cytochrome P450 (CYP) inhibition profiles. Radar plots and comparative tables were employed to visualize differences between structural analogues.

Results. The analysis showed that most derivatives maintain acceptable lipophilicity and solubility ranges, while some analogues demonstrated promising profiles in terms of balanced polarity and molecular size. Several compounds were predicted as potential inhibitors of CYP3A4 and CYP2C9 isoenzymes, highlighting their possible pharmacological activity. Despite moderate limitations in oral bioavailability, certain molecules exhibited favorable characteristics suggesting a good balance between stability and pharmacokinetic behavior. Structural features, such as alkyl chain length and substitution patterns, significantly influenced solubility, permeability, and drug-likeness scores. The data suggest that further optimization of polarity and molecular weight could improve gastrointestinal absorption while retaining beneficial pharmacological interactions. The antioxidant and antihypoxic potential of these molecules is supported by their structural features and predicted bioactivity, positioning them as attractive candidates for future biological screening.

Conclusions. The study provides a computational basis for selecting the most promising triazole-based derivatives for subsequent in vitro and in vivo testing, facilitating the design of compounds with optimized ADME properties and potential therapeutic application.