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Alzheimer’s disease is a chronic progressive degeneration disease of the central nervoussystem. At present, acetylcholinesterase inhibitors are the most effective drugs in the clinicaltreatment of the disease. It is reported that tacrine analogues, pyran-tacrine anddihydropyridine-tacrine, display good inhibitory activity on acetylcholinesterase, and on topof that, the compounds were demonstrated possessing antioxidation, efficacy to prevent Aβamylon protein deposition and neuroprotective activity, which make them possible treatmoderate even severe alzheimer’s disease. Based on the latest research achievements abroad,tacrine analogues and alkylene-linked pyran-tacrine dimers as acetylcholinesterase inhibitorswere synthesized and presented in this thesis.In the first part, the situation of alzheimer’s disease and developments in the research onacetylcholinesterase inhibitors were summarized. Then the general situation of structurallymodification of tacrine, synthesis and application of pyrans, pyran-tacrine anddihydropyridines were introduced. In order to research the acetylcholinesterase inhibitors ofpyran category, the second part focused on the synthesis of pyran and pyran-tacrine usingmalononitrile, aldehyde, dicarbonyl compound and cyclohexanone as the basic raw materialsthrough Knoevenagel condensation, Michael addition, Friedl nder condensation reaction andso on. The related compounds were characterized by1HNMR,13CNMR, IR. Then, the thirdpart focused on the synthesis of dihydropyridine using malononitrile, aldehyde, dicarbonylcompound and chlorethamin hydrochloride as the basic raw materials through Knoevenagelcondensation, Michael addition, amination, rearrangement, and so on, among which a newmethod of synthesizing oxo-dihydropyridines was discovered. The main products werecharacterized by1HNMR,13CNMR, IR and crystallography. At last, in order to obtainmultiple target point acetylcholinesterase inhibitors, the process of connecting tacrine and itsanalogues through flexible alkyl chain was discussed in the fourth part. Using glutaraldehyde,tacrine and pyran-tacrine as reactants, alkylene-linked pyran-tacrine dimmers were obtainedand characterized by1HNMR,13CNMR, IR.In the end, the key points of the research were summarized and the further study on theapplication of the new compounds was envisioned. As supporting components, the spectraldiagrams of main products were given in the appendix.
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