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Li, Qi; He, Siyu; Chen, Yao; Feng, Feng; Qu, Wei; Sun, Haopeng
European journal of medicinal chemistry, 10/2018, Volume: 158Journal Article
Alzheimer's disease (AD) is one of the most common neurodegenerative disorders in elderly people. Considering the multifactorial nature of AD, the concept of multi-target-directed ligands (MTDLs) has recently emerged as a new strategy for designing therapeutic agents on AD. MTDLs are confirmed to simultaneously affect diverse targets which contribute to etiology of AD. As the most potent approved drug, donepezil affects various events of AD, like inhibiting cholinesterases activities, anti-Aβ aggregation, anti-oxidative stress et al. Modifications of donepezil or hybrids with pharmacophores of donepezil in recent five years are summarized in this article. On the basis of case studies, our concerns and opinions about development of donepezil derivatives, designing of MTDLs, and perspectives for AD treatments are discussed in final part. Display omitted •We described multi-functional cholinesterase inhibitors based on donepezil.•Compounds with high activities and diverse functions are classified by their targets.•In final part, we put forward perspectives rarely mentioned in previous articles.
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