160845-90-9Relevant academic research and scientific papers
Novel multi target-directed ligands targeting 5-HT4 receptors with in cellulo antioxidant properties as promising leads in Alzheimer's disease
Lanthier, Caroline,Payan, Hugo,Liparulo,Hatat, Bérénice,Lecoutey, Cédric,Since, Marc,Davis, Audrey,Bergamini, Christian,Claeysen, Sylvie,Dallemagne, Patrick,Bolognesi, Maria-Laura,Rochais, Christophe
, (2019)
Facing the complexity of Alzheimer's disease (AD), it is now currently admitted that a therapeutic pleiotropic intervention is needed to alter its progression. Among the major hallmarks of the disease, the amyloid pathology and the oxidative stress are closely related. We propose in this study to develop original Multi-Target Directed Ligands (MTDL) able to impact at the same time Aβ protein accumulation and toxicity of Reactive Oxygen Species (ROS) in neuronal cells. Such MTDL were obtained by linking on a central piperidine two scaffolds of interest: a typical aminochlorobenzophenone present in numerous 5-HT4R agonists, and diverse antioxidant chemotypes. Interestingly, the most active compound 9g possesses a Ki of 12.7 nM towards 5-HT4R and an antioxidant activity in vitro and in cellulo.
Design, synthesis, and pharmacological evaluation of multitarget-directed ligands with both serotonergic subtype 4 receptor (5-HT4R) partial agonist and 5-HT6R antagonist activities, as potential treatment of Alzheimer's disease
Yahiaoui, Samir,Hamidouche, Katia,Ballandonne, Céline,Davis, Audrey,De Oliveira Santos, Jana Sopkova,Freret, Thomas,Boulouard, Michel,Rochais, Christophe,Dallemagne, Patrick
, p. 283 - 293 (2016/07/06)
5-HT4 receptor (5-HT4R) activation and blockade of the 5-HT6 receptor (5-HT6R) are known to enhance the release of numerous neurotransmitters whose depletion is implicated in Alzheimer's disease (AD). Furthermor
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
Rochais, Christophe,Lecoutey, Cédric,Gaven, Florence,Giannoni, Patrizia,Hamidouche, Katia,Hedou, Damien,Dubost, Emmanuelle,Genest, David,Yahiaoui, Samir,Freret, Thomas,Bouet, Valentine,Dauphin, Fran?ois,De Oliveira Santos, Jana S.,Ballandonne, Céline,Corvaisier, Sophie,Malzert-Fréon, Aurélie,Legay, Remi,Boulouard, Michel,Claeysen, Sylvie,Dallemagne, Patrick
, p. 3172 - 3187 (2015/04/27)
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. (Figure Presented).
1-PHENYLALKANONE 5-HT4 RECEPTOR LIGANDS
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, (2008/06/13)
The present invention relates to novel 5-HT 4 receptor ligands which are 1-(5-halo-4-aminophenyl) (C 2-6)alkan-1-one derivatives in which the 5-halo-4-aminophenyl group is substituted at its 2-position with (C 1-4)alkyloxy or phenyl(C 1-4)alkyloxy and optionally substituted at its 3-position with (C 1-4)alkyloxy or substituted at its 2-and 3-positions together with methylenedioxy or ethylenedioxy and the highest numbered carbon of the (C 2-6)alkan-1-one is substituted with di(C 1-4)alkylamino, morpholin-1-yl or pyrrolidin-1-yl or optionally substituted piperidin-1-yl, piperidin-4-yl, azacyclohept-1-yl, azabicyclo[2.2.1]hept-3-yl, azabicylo[2.2.2]oct-3-yl or azabicylo[3.2. 2] non-3-yl; and the pharmaceutically acceptable salts, individual isomers and mixtures of isomers and methods of using and making such derivatives.
