Design,Synthesis And Biological Evaluation Of MAO-B Selective Inhibitors

Parkinson’s disease(PD)is a long-term degenerative disorder of the central nervous system that mainly affects the motor system,seriously impacting on the health and living standards of the elderly.It has been found that monoamine oxidase B(MAO-B)has close relationship with PD and MAO-B can serve as a target for the development of PD drugs.Currently,some MAO-B inhibitors were approved for the treatment of PD.In addition,many structure diverse MAO-B selective inhibitors have been reported.However,these inhibitors have many problems,such as poor selectivity,nonideal potency and pharmacokinetic.Development of novel MAO-B inhibitors with high efficiency,high selectivity and safety is crucial.In this study,we designed MAO-B selective inhibitors using Rasagiline as the lead compound.Fragments were attached to Rasagiline to explore the hydrophobic pocket of MAO-B which is critical for the selectivity between MAO-A and MAO-B.25 novel compounds were synthesed and tested for their inhibition againt MAO-A and MAO-B.Some compounds were also tested for their potential inhibition against a few tumor cell lines.Among these 25 compounds,C14 is a highly selective MAO-B inhibitor with an IC50 of 20 nM,and a SI of 466,which has laid a foundation to further develop novel effective drugs for the treatment of PD.