Synthesis Of Analogues Related To Physostigmine And Structure/ Activity Relationships For Anticholinesterase Activity

Alzheimer's disease(AD) is a disorder with the central nervous system's degeneration that the progressive cognition declines and the memory loss is the major hallmarks.In clinical,AD patients first exhibit the decline of memory,then followed the appearance of intelligence fall off,aphemia,loss of the competence of judgement, hard to do exercise and completely lose the ability of normal self-action finaily.AD is a disease that has high rate of geting and death,so it becomes one of the problem that most hard to settle and which need to be resolved urgenly.Though the mechanism of AD is complex,the causations are not very clear,in the development of research,people find that there are several shortages of choline function in AD patient's brain,that are mainly the disorder of actylcholine's synthesis, secretion and the hydrolyze of actylcholinesterase,but the actylcholine is very important to peoples' learning and memory.Based on the "cholinergic hypothesis",to find the effective and selectivity actylcholinesterase inhibitors which could rise the function of cholin and improve the ability of cognition,became an important direction in the AD research.Nowadays,the nice actylcholinesterase inhibitors have huperzine A,galantamine,tacrine and physostigmine,but all of them have some defects.We have summarized these current inhibitors,then decided to choice the physostigrnine for restructuring,hoping to obtain the effective lead compound. Primarily,to substitute the methyl on atom N from the carbamate of physostigmine with aryl,and select the methods of synthesis and last disposal which was mild reaction condition,simple operation.We used the rabbits' brain tissue and plasma as enzyme source for actylcholinesterate and butylcholinesterate.Studing anticholinesterate activity of the related compound to physostigrnine by improved spectrophotometric method of Ellman et al,for the results could direct this kind of compound's future restructuring and develop greater lead compound.