阿尔茨海默病（AD）是一种严重威胁老年人身体健康的重大疾病。已上市的AD治疗药物主要为单靶点的AChE抑制剂，只能改善认知功能症状，不能治愈AD。针对AD复杂发病机制的特点，本项目试图发展AChE抑制/MAO-B抑制/金属离子螯合/抗氧化四功能抗AD活性化合物。在前期研究中，我们已发现一个能够改善痴呆小鼠记忆认知能力三功能抗AD候选药物。在此基础上，本项目采用多靶点药物设计策略的“拼合原理”，将MAO-B抑制剂药效团炔丙胺连接到三功能抑制剂抑制活性不敏感结构区域，通过结构修饰优化，全面提高衍生物活性，减小衍生物毒性，优化衍生物理化性质，以获得活性强、毒性低、具有良好类药性质的四功能抗AD候选药物，为开发具有我国自主知识产权的多靶点抗AD药物提供良好的临床前候选药物。本项目的实施将为多功能抗AD药物的研发提供优良的候选药物和新的组合治疗思路。

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder which severely threatens the health of the elderly people worldwide. To date, the drugs listed for the treatment of AD are mainly acetylcholinesterase (AChE) inhibitors. As single-target anti-AD drugs, they only exhibit modest improvements in memory and cognitive function but do not Cure AD. Given its complex etiology, we attempt to develop tetrafunctional anti-AD agents with AChE inhibition, monoamine oxidase B (MAO-B) inhibition, metal chelation and antioxidant activity. In the previous research work, we have found an excellent trifunctional anti-AD candidate drugs with improved memory and cognitive function in scopolamine-induced amnesia mice. Based on the fact above and multi-target design strategy, we further plan to design and synthesize a series of novel tetrafunctional anti-AD agents by connecting the propargylamine pharmacophore of MAO-B inhibitors to the inactive structure region of our trifunctional inhibitors, hoping to discover some novel type anti-AD candidate drugs with more excellent therapeutic effects, less toxicities and good druggability. Implementation of this project will provide excellent candidate drugs with independent intellectual property rights in our country and a new combination therapy idea for the development of anti-AD drugs.