Design,Synthesis And Biological Activity Of Novel Chiral Monoamine Oxidase Selective Inhibitors

At present,the incidence of neurodegenerative diseases has begun to appear to be younger,and serious patients will choose to commit suicide to put an end to their lives.Because of the harm caused by these diseases,and even seriously affecting normal life,the prevention and treatment of mental diseases have become the focus of national mental health work.Many small molecule inhibitors have been synthesized in the treatment of diseases,such as tricyclic drugs,selective serotonin inhibitors,monoamine oxidase inhibitors?MAOIs?,and monoamine oxidase inhibitors have become the main subject,and MAOIs are reversible.Inhibitors and irreversible inhibitors,but in clinical trials,various inhibitors have the disadvantage of large side effects or poor selectivity,so it is an urgent task to develop small molecule inhibitors with reversibility,selectivity and side effects.In this paper,we will further study small molecule inhibitors with high selective reversibility,mainly synthesize a series of choral compounds with phenethylamine derivatives,and conduct cytotoxicity experiments and enzyme inhibition selection for these compounds.Sexual experimentation.The synthesis is mainly carried out by using phenethylamine having a choral structure as a starting material,dissolved in refined acetonitrile,and nucleophilic substitution reaction with propargyl bromide to form first step intermediate 2,and under basic conditions,intermediate 2 and NaCNBH3 dissolved in methanol to undergo reductive aminolysis reaction to obtain intermediate tertiary amine 3,followed by dissolving the tertiary amine and hydrochloric acid in diethyl ether solution to form the target compound tertiary amine salt 4.The structure of the compound was established by mass spectrometry?MS?,nuclear magnetic resonance?¹H-NMR?,nuclear magnetic resonance(¹³C-NMR)and infrared spectroscopy?FT-IR?.Cytotoxicity studies were performed on eight targets compounds by CCK-8 method.Some compounds showed cytotoxicity to mouse fibroblasts?L929?,but most of the compounds were not toxic to L929 cells.Among the eight compounds,compounds 4b and 8b showed some toxicity to L929,probably due to the influence of chlorine substituents,which could be altered by structural optimization.MAO inhibition selectivity experiments were performed on the synthesized eight compounds.Compounds 4b and 4c exhibited high selectivity to MAO-A compared to compounds 8b and 8c.It can be observed that the R configuration of the compound relative to the S configuration The compound has an enzyme inhibitory activity.Compound 4a did not exhibit high inhibition selectivity for the two isotherms of MAO,while 4b showed strong inhibitory activity against MAO-A,so the electron donating ability of the substituent also affected the activity of the enzyme.