Design of novel nicotinamides as potent and selective monoamine oxidase a inhibitors

A series of nicotinamide derivatives (1-26) have been designed, synthesized and evaluated in vitro for their monoamine oxidase inhibitory activity and selectivity. Most of these synthesized compounds proved to be potent, and selective inhibitors of MAO-A rather than of MAO-B. 5-Chloro-6-hydroxy-N-(2-morpholinoethyl)nicotinamide (13) displayed the highest MAO-A inhibitory potency (IC50 = 0.045 μM) and a good selectivity. 2-Bromo-N-(2-morpholinoethyl)nicotinamide (3) was the most potent MAO-B inhibitor with the IC50 value of 0.32 μM, but it was not selective. Molecular dockings of compound 13 were performed in order to give structural insights regarding the MAO-A selectivity.