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

Abstract

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).