Novel multitarget-directed ligands (MTDLs) with acetylcholinesterase (AChE) inhibitory and serotonergic subtype 4 receptor (5-HT4R) agonist activities as potential agents against Alzheimer's disease: the design of donecopride

Journal of Medicinal Chemistry
Christophe RochaisPatrick Dallemagne

Abstract

In this work, we describe the synthesis and in vitro evaluation of a novel series of multitarget-directed ligands (MTDL) displaying both nanomolar dual-binding site (DBS) acetylcholinesterase inhibitory effects and partial 5-HT4R agonist activity, among which donecopride was selected for further in vivo evaluations in mice. The latter displayed procognitive and antiamnesic effects and enhanced sAPPα release, accounting for a potential symptomatic and disease-modifying therapeutic benefit in the treatment of Alzheimer's disease.

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Citations

Mar 31, 2016·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Michalina HebdaBarbara Malawska
Apr 16, 2016·Future Medicinal Chemistry·Michela RosiniAnna Minarini
May 21, 2016·Frontiers in Neuroscience·Rebecca E HughesRona R Ramsay
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Aug 3, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·François-Xavier ToubletChristophe Rochais
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Dec 31, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Benjamin GuieuPatrick Dallemagne
Apr 10, 2016·European Journal of Medicinal Chemistry·Julien LalutChristophe Rochais
Apr 12, 2021·Bioorganic & Medicinal Chemistry Letters·Tanay DalviBichismita Sahu
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Jul 3, 2021·International Journal of Molecular Sciences·Francesca Serena AbatematteoCarmen Abate

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