Designing a molecule for targets of CNS diseases presents significant challenges as the blood-brain barrier (BBB) restricts the migration of molecules to the brain more strongly than to other body compartments. If the designed molecule is amenable to tautomerism, it may have multiple forms under physiological conditions. It should be present in sufficient amounts or exclusively to allow entry of the predominant tautomer. Edaravone is known to exist in anionic and tautomeric forms; however, a slight modification to the phenyl ring led exclusively a keto tautomer which had good BBB permeability, while the replacement of the methyl group by trifluoromethyl led to only the enol form with poor BBB permeability. 12