Furthermore, with the aid of quantum-mechanics (QM) level binding energy calculations, we assessed the effect on TbPTR1 binding energies of different halogen substitutions to the phenyl ring of compounds sharing the same scaffold. The QM calculation results, together with the TbPTR1 activity assays and crystallographic data for the selected synthesized compounds, provide insights into the SAR and improved understanding of the binding modes of the halogenated compounds.