Synthesis And Biological Activity Of Quinoline Derivatives Derived From Morpholine Or N-ethylpiperazinyl Groups

Senile dementia is a common disease that currently threatens the health of the elderly,it mainly manifests itself as cognitive impairment and behavior disorder,and the serious person even loses the ability of life self-care.Among them,alzheimer's disease is the main disease of senile dementia,the pathogenesis of alzheimer's disease is still unclear,the mainstream doctrine includes the cholinergic hypothesis,the A?toxicity hypothesis and the tau-hypothesis.Treatment of alzherimer's is mainly based on cholinesterase inhibitors,antiamyloidosis,NMDA receptor antagonists and amyloid tau-proteins.With the development of society,the problem of population aging is becoming more and more serious,the incidence of AD is higher and higher.Clinically the first drug treatment of AD is acetylcholinesterase drug?tacrine?,in view of tacrine is a quinoline as a mother ring and has good pharmacodynam ic activity,So we studied cholinesterase drugs based on quinolinoid.Morphine and ethyl piperazine are also active,We use a combination of principles to find the two Cholinesterase activity of new compounds was studied.It is made from oxalic acid,the compounds and derivatives of morphine or N-ethyl piperazine were synthesized by a serise of reactions.The structure of the compound was characterized by,¹H-NMR,¹³C-NMR,HR-ESI-MS,IR,and the activity of cholinesterase was explored.The results showed that the substituting group of aniline group can enhance its activity when it is absorbed by the electron group?chloride ion?,when the substituted group of aniline is for the electron group?hydroxy?,it can reduce the activity of cholinesterase.The indicates that the aniline group containing the electron absorption is helpful to the binding of the catalytic activity site of CAS in the bottom of cholinesterase.It was found that the quinoline compounds containing aniline group have good activity,in order to explore the drugs of higher cholinesterase activity,we can further study the location,size and number of the substituents.It can also modify and modify the groups on bromochloropropane to synthesize higher active compounds and explore better AD drugs,alleviating and improving the health risks of alzheimer's disease to the elderly.