Structure-activity relationships within the 4-phenylquinazoline-2-carboxamide series of Translocator Protein (TSPO) ligands have been explored further, by the synthesis and TSPO binding affinity evaluation of N-benzyl-N-ethyl/methyl derivatives variously decorated at 6-, 2'-, 4'-, and 4″-positions. Most of compounds showed high affinity with Ki values in the nanomolar/subnanomolar range. A pharmacophore model was developed and employed to better address SAR data presented by the new TSPO ligands. A subset of the new compounds (1, 4, 8 and 15) were tested for their ability to inhibit the viability of human glioblastoma cell line U343. The observed antiproliferative effect was demonstrated to be specific for compound 15, endowed with the best combination of binding affinity and efficacy. Furthermore, the ability of 15 to induce mitochondrial membrane dissipation (Δψm) substantiated the intracellular pro-apoptotic mechanism activated by the binding of this class of ligands to TSPO.