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A new lead compound has been designed as an antiangiogenic EGFR inhibitor that has the pharmacophoric characteristics to bind with the catalytic pocket of EGFR protein. The designed lead compound is a (para-chloro)acetamide derivative of the alkaloid, theobromine, (<b>T-1-PCPA</b>). At first, we started with deep density functional theory (DFT) calculations for <b>T-1-PCPA</b> to confirm and optimize its 3D structure. Additionally, the DFT studies identified the electrostatic potential, global reactive indices and total density of states expecting a high level of reactivity for <b>T-1-PCPA</b>. Secondly, the affinity of <b>T-1-PCPA</b> to bind and inhibit the EGFR protein was studied and confirmed through detailed structure-based computational studies including the molecular docking against EGFR^WT and EGFR^T790M, Molecular dynamics (MD) over 100 ns, MM-GPSA and PLIP experiments. Before the preparation, the computational ADME and toxicity profiles of <b>T-1-PCPA</b> have been investigated and its safety and the general drug-likeness predicted. Accordingly, <b>T-1-PCPA</b> was semi-synthesized to scrutinize the proposed design and the obtained in silico results. Interestingly, <b>T-1-PCPA</b> inhibited in vitro EGFR^WT with an IC₅₀ value of 25.35 nM, comparing that of erlotinib (5.90 nM). Additionally, <b>T-1-PCPA</b> inhibited the growth of A549 and HCT-116 malignant cell lines with IC₅₀ values of 31.74 and 20.40 µM, respectively, comparing erlotinib that expressed IC₅₀ values of 6.73 and 16.35 µM, respectively.