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Novel Multitarget-Directed Ligands (MTDLs) with Acetylcholinesterase (AChE) Inhibitory and Serotonergic Subtype 4 Receptor (5-HT 4 R) Agonist Activities As Potential Agents against Alzheimer’s Disease: The Design of Donecopride
- Source :
- Journal of Medicinal Chemistry, Journal of Medicinal Chemistry, 2015, 58 (7), pp.3172-3187. ⟨10.1021/acs.jmedchem.5b00115⟩, Journal of Medicinal Chemistry, American Chemical Society, 2015, 58 (7), pp.3172-3187. ⟨10.1021/acs.jmedchem.5b00115⟩
- Publication Year :
- 2015
- Publisher :
- HAL CCSD, 2015.
-
Abstract
- International audience; 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.
- Subjects :
- Agonist
Male
medicine.drug_class
Aché
[CHIM.THER] Chemical Sciences/Medicinal Chemistry
Guinea Pigs
Drug Evaluation, Preclinical
Mice, Inbred Strains
[CHIM.THER]Chemical Sciences/Medicinal Chemistry
Pharmacology
Serotonergic
Inhibitory postsynaptic potential
Crystallography, X-Ray
Ligands
Alzheimer's Disease
MTDL
chemistry.chemical_compound
Serotonin 5-HT4 Receptor Agonists
Structure-Activity Relationship
Piperidines
In vivo
Alzheimer Disease
Drug Discovery
medicine
Toxicity Tests, Acute
Structure–activity relationship
Animals
Humans
Computer Simulation
Molecular Targeted Therapy
Receptor
Aniline Compounds
Acetylcholinesterase
language.human_language
3. Good health
Donecopride
Mice, Inbred C57BL
Memory, Short-Term
chemistry
Drug Design
language
Molecular Medicine
Cholinesterase Inhibitors
Receptors, Serotonin, 5-HT4
5-HT4 Receptors
Subjects
Details
- Language :
- English
- ISSN :
- 00222623 and 15204804
- Database :
- OpenAIRE
- Journal :
- Journal of Medicinal Chemistry, Journal of Medicinal Chemistry, 2015, 58 (7), pp.3172-3187. ⟨10.1021/acs.jmedchem.5b00115⟩, Journal of Medicinal Chemistry, American Chemical Society, 2015, 58 (7), pp.3172-3187. ⟨10.1021/acs.jmedchem.5b00115⟩
- Accession number :
- edsair.doi.dedup.....2c5fe2081ee851cedc243f21b1c65a5a