| Excessive iron ions in the brain can cause neurotoxicity and aggravate the condition of Alzheimer's disease.Iron ions can be chelated by 3-Hydroxypyridin-4-one compounds,which can reduce oxidative stress in the brain,and therefore protect neurons.Monoamine oxidase catalyzes the oxidation of various amines in the body and produces toxic substances such as hydrogen peroxide and aldehydes that are harmful to nerves.Coumarin compounds have a monoamine oxidase inhibitory effect,thereby reducing the production of toxic substances in the brain and reducing the state of Alzheimer's disease.Based on the pathogenesis of Alzheimer's disease and the structure-activity relationship between 3-hydroxypyridin-4-one compounds and coumarin compounds,the iron chelator-monoamine oxidase inhibitor drug for Alzheimer disease was synthesized by the click chemistry method.Moreover,a new synthesis method for the reduction of azide to amine using boron tribromide as reducing agent was also designed.A series of amino-substituted hydroxypyridinone compounds were synthesized by this method.This thesis consists three chapters: The first chapter summarizes the pathogenesis of Alzheimer's disease and the research progress of anti-Alzheimer's disease drugs.Besides,the development and clinical application of 3-hydroxypyridin-4-ones and coumarins were reviewed.In the second chapter,the synthetic method for azido-3-hydroxypyridin-4-ones was designed,and 3-,4-,and 7-alkynyl coumarins were also designed.These two compounds were attached to obtain the double target compound by the click chemistry method using triazole as a linker.The activity of target compounds was measured by spectrophotometry and fluorescence method,and the results were evaluated briefly.In the third chapter,a new synthesis method for amine derivatives with azide-based compounds as substrates and boron tribromide as reducing agent was designed.The reaction conditions were optimized and the applicability of the substrates were investigated. |
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