Synthesis of a series of unsaturated ketone derivatives as selective and reversible monoamine oxidase inhibitors

Abstract

We have synthesized three categories of alpha,beta-unsaturated carbonyl derivatives and evaluated their MAO-A and MAO-B inhibitory activities. Among them, compound 10b including alpha, beta-unsaturated ketone group showed the most potent and selective MAO-B inhibitory activity (IC50 human MAO-B 16 nM, >6000-fold selective vs MAO-A) and compound 10b exhibited good reversibility compared with selegiline, a well-known irreversible MAO-B inhibitor. However, both a, b-unsaturated amide and ester derivatives exhibited weaker MAO-B inhibition potencies. The docking studies provided insights into the possible binding modes and the key interaction sites of the synthesized MAO-B inhibitors. (C) 2015 Elsevier Ltd. All rights reserved.