Synthesis,Molecular Docking And Antidepressant Activity Of Morpholine Derivatives

Depression is a mental illness with high incidence and high risk.Neurotransmitter imbalance,immune dysfunction,neuroendocrine disorders,abnormal neuroplasticity and genetic factors are all closely related to the onset of depression.The new drugs mainly include:selective serotonin(5-HT)reuptake inhibitor,norepinephrine(NE)reuptake inhibitor,.Indol usually related to the function of G protein receptor,especially with serotonin The receptor transmits neuronal signals.Studies have shown that the chemical structure of the neurotransmitter serotonin is based on an electron-rich aromatic anthracene ring.According to this structural feature of the neurotransmitter serotonin,when the structure of the antidepressant compound is designed,the anthracycline ring can be introduced at the appropriate position of the morpholine,thereby reducing the reuptake of the neurotransmitter serotonin,thereby improving the protrusion.The content of neurotransmitter serotonin in the gap to achieve antidepressant.Morpholine derivatives were synthesized from 3-methyl-4-nitrobenzoic acid and4-methyl-3-nitrobenzoic acid by using Batcho-Leimgruber,the structures of the products were proven by means of ~1H NMR,mass spectroscopic data.2A65,which is highly homologous to NET,was used as a receptor to dock with the target compound.The force swimming test(FST)was used to evaluate the products'antidepressant activity.The antidepressant activity of the target compound was evaluated by molecular docking analysis and mouse forced swimming pharmacological experiments.The research content of this topic is as follows:1 The morpholine ring was the main component,and the anthracene ring was introduced at the N position of the morpholine ring.At the same time,a new organic synthesis route was designed by consulting a large number of literatures,and a new target compound was successfully synthesized.Its structure was subjected to 1H NMR,IR and MS confirmed.2 The 2A65 protein was used as a template,and the target protein NET was obtained by means of homologous modeling,and it was defined as a receptor protein.The target compound is then mapped using ChemDraw's mapping software,and its structure is optimized and then defined as a small molecule ligand.Using the autodock4.0,the receptor protein and the small molecule ligand were sequentially molecularly docked?3 Using the classic anti-depressant animal experimental model-mouse forced swimming experiment(FST),the antidepressant fluoxetine was used as a positive control to re-evaluate the antidepressant activity between the enantiomers.