- 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.
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 (2015-03-21)
Christophe Rochais, Cédric Lecoutey, Florence Gaven, Patrizia Giannoni, Katia Hamidouche, Damien Hedou, Emmanuelle Dubost, David Genest, Samir Yahiaoui, Thomas Freret, Valentine Bouet, François Dauphin, Jana Sopkova de Oliveira Santos, Céline Ballandonne, Sophie Corvaisier, Aurélie Malzert-Fréon, Remi Legay, Michel Boulouard, Sylvie Claeysen, Patrick Dallemagne
PMID25793650
摘要
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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ChemiSCREEN Membrane Preparation Recombinant Human 5-HT4B Serotonin Receptor, Human 5-HT4 GPCR membrane preparation for Radioligand binding Assays & GTPγS binding.