ADME Profile Calculation and Drug Similarity Study of New 1,2,4-Triazole Derivatives Containing 2-Bromo-5-Methoxyphenyl Radical

Czech version

Authors: Mykola Skoryi ¹; Roman Shcherbyna ¹; Sergii Kulish ¹; Volodymyr Salionov ²; Oleksandra Cherchesova ³
Authors‘ workplace: Department of Toxicological and Inorganic Chemistry, Faculty of Pharmacy, Zaporizhzhia Medical and Pharmaceutical University, Zaporizhzhya, Ukraine ¹; Department of Biological Chemistry, Faculty of Pharmacy, Zaporizhzhia Medical, and Pharmaceutical University, Zaporizhzhya, Ukraine ²; Professional Medical and Pharmaceutical College of PJSC „Higher Education Institution“ MAUP, Kyiv, Ukraine ³
Published in: Čes. slov. Farm., 2025; 74, 1-5
doi: https://doi.org/10.36290/csf.2025.024

Overview

Introduction: Evaluating ADME (absorption, distribution, metabolism, excretion) profiles is critical in drug development to ensure bioavailability, efficacy, and safety. 1,2,4-Triazole derivatives, particularly those with a 2-bromo-5-methoxyphenyl radical, are promising due to their broad biological activities, yet their pharmacokinetic properties are insufficiently studied. The objective of this study was to predict the ADME characteristics and drug-likeness of these compounds to identify candidates with optimal pharmacokinetic potential for therapeutic applications.

Objectives: This study aimed to assess the ADME profiles of new 1,2,4-triazole derivatives incorporating a 2-bromo-5-methoxyphenyl fragment using in silico methods and evaluate their compliance with drug-likeness criteria, such as Lipinski’s Rule of 5, for potential pharmaceutical development.

Methods: A series of 28 derivatives, including 5-(2-bromo-5-methoxyphenyl)-4-R-1,2,4-triazole-3-thiols (3a–3d), thioacetic acids (4a–4d), and esters (5a–5t), were analyzed via the Molinspiration Property Calculator. Key parameters assessed were lipophilicity (miLogP), polar surface area (TPSA), molecular weight (MW), hydrogen bond donors (nOHNH) and acceptors (nON), rotatable bonds (nrotb), and Lipinski rule violations (nviolations).

Results: Thiol derivatives (3a–3d) showed moderate lipophilicity (miLogP 3.02-3.33) and TPSA (39.95–50.81 Å²), suggesting good permeability. Thioacetic acids (4a–4d) had higher TPSA (77.25–88.11 Å²) and lower miLogP (2.46–3.81), indicating enhanced solubility but reduced permeability. Esters (5a–5t) varied widely in lipophilicity (miLogP 3.08–5.86), with three compounds (5l, 5p, 5t) exceeding Lipinski’s miLogP limit (> 5). Most compounds complied with Lipinski’s Rule, with MW ranging from 286.15–476.40 g/mol and nrotb from 2–10.

Conclusion: Structural modifications significantly influenced ADME profiles, with thiols and thioacetic acids showing favorable drug-like properties. High-lipophilicity esters may require optimization. These findings support the potential of these triazole derivatives as drug candidates, warranting further pharmacological studies.