Selective and potent monoamine oxidase type B inhibitors: substituted semicarbazones and acylhydrazones of aromatic aldehydes and ketones

Summary The synthesis and the evaluation of the monoamine oxidase A and B inhibitory activities of 21 new substituted acylhydrazones of various aromatic aldehydes and 4-(benzyloxy)acetophenone, and four substituted semicarbazones of benzaldehyde and 4-(benzyloxy)benzaldehyde, are described. The 4-(benzyloxy)phenyl group contributing to a high lipophilicity led to the most active compounds. One of these, compound 3g (IC 50 = 3 nM, MAO A/MAO B selectivity > 33 000), was found to act as a reversible and probably tight-binding inhibitor. The studied acyclic hydrazones and semicarbazones are structurally related to other reversible and potent inhibitors, eg , heterocyclic compounds such as 1,3,4-oxadiazol-2(3 H )-one derivatives in which the hydrazono group is intracyclic. Some of these new inhibitors might find use in the symptomatic treatment of neurodegenerative processes.