The Research On Synthesis And Antidepressant Biological Activity Of5-phenyl-2-Aryl-2-Morpholinols

The researching and development of antidepressant has become a new area of thepharmaceutical industry, when the depression patients are increasing. Themorpholinol compounds is known to have various functions and bioactivities suchasantidepressant. which is getting attention by Medicinal chemists effecti. On thebasis of the success of which Researcher. The aim of this dissertation is to synthesizesand screens5-phenyl-2-Aryl-2-morpholinols with antidepressant active to providesthe lead compounds for the new medicine. The main research works are described asfollows:(1) Through the introduction of different substituents,experimenter carried out thealteration on the structure of2-aryl morpholine we won eight new2-aryl-2-morpholinol by bring the new substituent to the aromatic rings.The target compounds structureafter IR，1HNMR,MS corroboration.(2) Design routes of synthetic2-aryl-2-morpholinol hydrochloride with2-aminopropanol. We got the target compound by four step reactions: Friedel-Crafts acylation，arylketones of-bromination, ammonification and acidification. The results showedthe synthesis reaction is short time， high yield，mild reaction conditions and uselessToxic solvents. It is a Practical value route.(3) After carry out uniform test design and simplex optimization, the optimumreaction conditions of5-phenyl-3-dimethyl-2-（3-fluorophenyl）-2-morpholinolhydrochloride were obtained when the mole ratio of mfluoro-a-bromopropiophenoneto phenylglycinol was l:4, the temperature was4o-50℃, and the reacting time was1h.(4) Antidepressant activity of the eight target products was evaluated by “behavioraldespair” model by Porsolt forced swimming test and tail suspension test. The resultsshowed that compound one and compound four compared to the blank control couldsignificantly shorten mice immobility time.These compounds may be the new leadcompounds in antidepressant drug, which make sure that the compounds are worth ofresearch in the future.