An extensive study was performed to develop a series of (pyrrolo-pyridin-5-yl)benzamides as reversible MAO-B inhibitors. Compounds 14 (NTZ-2020, hMAO-B IC50 = 1.11 nM, Ki = 0.56 nM, >9000-fold selective versus MAO-A) and 15 (NTZ-2027, hMAO-B IC50 = 3.27 nM, Ki = 1.45 nM, SI > 3058) are identified as the most promising BBB permeable derivatives within the series of (1H-pyrrolo[3,2-b]pyridine-5-yl)benzamides, combining both high potency and selectivity with optimal physicochemical and drug-like properties required for CNS active drugs. Extended photophysical analysis, including single X-ray analysis, quantum-chemical calculations and spectroscopic experiments provided insights into their tautomerism and structural behavioral, which relates to their biologically active form. The reversible MAO-B inhibitor 14 (NTZ-2020) exhibits a neuroprotective effect on cortical neuron survival and induces neurite network outgrowth. These effects are associated with a good BBB penetration of 14 that was confirmed in a triple cell neurovascular unit (NVU) model.