<p>The creation of new molecular structures that can interact precisely with biological targets remains paramount in drug design. In this paper, we provide a streamlined strategy that focuses on the synthesis of isoxazolidinyl-based nitrogen molecules, through a highly regioselective, diastereoselective, and catalyst-free 1,3-dipolar cycloaddition reaction, between amine-substituted acrylates and aryl nitrones. This synthetic method is simple, efficient, and operates under mild conditions, with excellent functional group tolerance. The ensuing cycloaddition reaction yields various isoxazolidinyl-linked compounds, incorporating three distinct pharmacophore groups: morpholine, piperazine, and imidazole moieties. The synthesized molecules were characterized using a combination of techniques including: ¹H, ¹³C, ¹⁹F NMR, IR-FTIR, and ESI-HRMS. Furthermore, a molecular docking study was performed using EGFR tyrosine kinase (PDB ID: 1M17 and 4HJO), as a target protein, to explore its binding interaction profile. All compounds interacted with the target protein with moderate to high affinity, with some derivatives exhibiting superior interactions. The predicted properties of ADMET indicated that most compounds displayed promising pharmacokinetic and drug-like properties. Our advanced synthesis expands the possibilities of drug design and promises advances in medicinal chemistry, inspiring further innovations and new therapeutic agents.</p> Graphical Abstract <p></p>