Syntheses Of 4-N-phenylaminoquinoline Derivatives And Research On Their Cholinesterase Inhibition Activities

Senile dementia is a manifestation of the human brain dysfunction,characterized by the decline of personality change and behavior.Alzheimer's disease is the main symptoms of dementia.With the speeding up of the world's population aging process,the number of alzheimer disease(AD)increased year by year.There are two kinds of cholinesterase(ChEs)in the central nervous system: acetylcholinesterase(AChE)and butyrylcholinesterase(BChE).Drug currently used in clinical treatment of AD is mainly acetylcholinesterase(AChE)inhibitors.Studies have also shown that it is effective inhibitors for treating AD that can simultaneously acting on the two kinds of cholinesterase.Quinoline derivatives and their analogues has many physiological activity,widely used in new drugs.Tacrine was used as AChE inhibitors for the treatment of AD.In recent years,a large number of studies have shown that the structures of the 4-N-phenylaminoquinoline derivatives have the activity of stronger cholinesterase inhibition and protecting nerve cells.Based on this,we synthesized the first 24 kinds of 4-N-phenylaminoquinoline derivatives by 10 or 11 route steps,and the anti-cholinesterase activities were evaluated using Ellman assay.The testing results show that all compounds have inhibitory activity on acetylcholinesterase,especially the 10 a,10c,10 e,12,which their all IC50 values are less than 1?mol/L.For butyrylcholinesterase inhibition activity,the activity of 10 a,12,13 is significant,stronger than the positive control galantamine.This thesis demonstrated that electron-withdrawing groups of 4-N-phenylaminoquinoline derivatives strengthen its ChE inhibition activity,and the electronic groups reduce its activity.In addition,the stretched-out anmine group in quinoline ring greatly improved the cholinesterase inhibition of target compounds.Quaternary ammonium salt moiety can significantly increase the inhibitory activity,and 1-methyl piperazinyl can be beneficial to biological membrane and the central nervous system.The structure-activity relationship for this type compounds deserve further study deeply,expecting to explore better drug of AD.