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Expert Opin Drug Discov. 2019 Jun 5:1-13. doi: 10.1080/17460441.2019.1623201. [Epub ahead of print]

Developments with multi-target drugs for Alzheimer's disease: an overview of the current discovery approaches.

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a Department of Chemistry in Pharmaceutical Sciences, Faculty of Pharmacy , Complutense University of Madrid , Madrid , Spain.


Introduction: Alzheimer's disease (AD), the most common type of dementia among older adults, is a chronic neurodegenerative pathology that causes a progressive loss of cognitive functioning with a decline of rational skills. It is well known that AD is multifactorial, so there are many different pharmacological targets that can be pursued. Areas covered: The authors highlight the strategic value of privileged scaffolds in a multi-target lead compound generation against AD, exploring the concept of multi-target design, with a special emphasis on hybrid compounds. Hence, the most promising building blocks for designing and synthesizing hybrid anti-AD drugs are shown, while also presenting the more advanced hybrid compounds. Expert opinion: The available therapeutic arsenal for AD, designed under the traditional paradigm of 'one-drug/one target/one-disease', is based on the inhibition of brain acetylcholinesterase (AChE) to increase acetylcholine (ACh) levels. However, this classical approach has not been sufficiently effective when used to treat any multifactor-depending pathology (cancer, diabetes or AD). The multi-target drug concept has been quickly adopted by medicinal chemists. The basic research developments reported in recent years are a solid foundation that will pave the way for the construction of future AD therapeutics.


Alzheimer’s disease; current hypotheses; multi-target direct ligand; privileged building blocks

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