3-Acetyl-2,5-diaryl-2,3-dihydro-1,3,4-oxadiazoles: a new scaffold for the selective inhibition of monoamine oxidase B.

3-Acetyl-2,5-diaryl-2,3-dihydro-1,3,4-oxadiazoles were designed, synthesized, and tested as inhibitors against human monoamine oxidase (MAO) A and B isoforms. Several compounds, obtained as racemates, were identified as selective MAO-B inhibitors. The enantiomers of some derivatives were separated by enantioselective HPLC and tested. The R-enantiomers always showed the highest activity. Docking study and molecular dynamic simulations demonstrated the putative binding mode. We conclude that these 1,3,4-oxadiazoles derivatives are promising reversible and selective MAO-B inhibitors.