ADME Profiling of Quinoxaline-Based Oxazole Derivatives for Drug-Likeness Assessment
摘要
A series of quinoxaline-based oxazole derivatives (4a–4p) were synthesized via a multicomponent reaction and subjected to comprehensive ADME (absorption, distribution, metabolism, and excretion) profiling using SwissADME to evaluate their pharmacokinetic properties and drug-likeness. The compounds, characterized by IR, NMR, and mass spectrometry, exhibited topological polar surface area (TPSA) values primarily around 76.2 Å2, indicating good membrane permeability, except for 4e and 4m with higher TPSA (122.0 Å2) and predicted low gastrointestinal (GI) absorption. The values of logP (3.98–5.53) suggested moderate to high lipophilicity, with compounds 4a, 4d, and 4h slightly exceeding Lipinski’s threshold but retaining high GI absorption. Poor aqueous solubility (ESOL logS: –6.69 to –7.55) highlighted a need for formulation strategies. None of the compounds crossed the blood–brain barrier, and most were non-substrates for P-glycoprotein, except 4f and 4n. Only 4f and 4n inhibited CYP2D6, with no CYP3A4 inhibition observed. All compounds, except 4i, complied with Lipinski’s Rule of Five, and synthetic accessibility scores (3.64–4.16) indicated feasible synthesis. Compounds 4a, 4d, 4f, and 4h emerged as promising candidates for further optimization due to their balanced ADME profiles.