donecopride   Click here for help

GtoPdb Ligand ID: 10584

Synonyms: compound 1 [PMID: 25793650] | MR31147 [2]
Compound class: Synthetic organic
Comment: Donecopride is a small molecule that exhibits potent dual actions as an acetylcholinesterase (AChE) inhibitor and as a partial 5-HT4 receptor agonist [4]. It is a hybrid molecule that combines structural components from the AChE inhibitor donepezil, and the 5-HT4 agonist RS 67333 [1] [2]. Donecopride is predicted to provide a combination of symptomatic and disease-modifying effects that are considered to offer therapeutic utility in Alzheimer's disease [3,5].
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 3
Hydrogen bond donors 1
Rotatable bonds 7
Topological polar surface area 55.56
Molecular weight 392.22
XLogP 4.84
No. Lipinski's rules broken 0
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Canonical SMILES COc1cc(N)c(cc1C(=O)CCC1CCN(CC1)CC1CCCCC1)Cl
Isomeric SMILES COc1cc(N)c(cc1C(=O)CCC1CCN(CC1)CC1CCCCC1)Cl
InChI InChI=1S/C22H33ClN2O2/c1-27-22-14-20(24)19(23)13-18(22)21(26)8-7-16-9-11-25(12-10-16)15-17-5-3-2-4-6-17/h13-14,16-17H,2-12,15,24H2,1H3
1. Eglen RM, Bonhaus DW, Johnson LG, Leung E, Clark RD. (1995)
Pharmacological characterization of two novel and potent 5-HT4 receptor agonists, RS 67333 and RS 67506, in vitro and in vivo.
Br J Pharmacol, 115 (8): 1387-92. [PMID:8564196]
2. Lecoutey C, Hedou D, Freret T, Giannoni P, Gaven F, Since M, Bouet V, Ballandonne C, Corvaisier S, Malzert Fréon A et al.. (2014)
Design of donecopride, a dual serotonin subtype 4 receptor agonist/acetylcholinesterase inhibitor with potential interest for Alzheimer's disease treatment.
Proc Natl Acad Sci USA, 111 (36): E3825-30. [PMID:25157130]
3. Lecoutey C, Rochais C, Genest D, Butt-Gueulle S, Ballandonne C, Corvaisier S, Dulin F, Lepailleur A, Sopkova-de Oliveira Santos J, Dallemagne P. (2012)
Synthesis of dual AChE/5-HT4 receptor multi-target directed ligands.
Medchemcomm, 3 (5): 627-634. DOI: 10.1039/C2MD20063E
4. Rochais C, Lecoutey C, Gaven F, Giannoni P, Hamidouche K, Hedou D, Dubost E, Genest D, Yahiaoui S, Freret T et al.. (2015)
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.
J Med Chem, 58 (7): 3172-87. [PMID:25793650]
5. Rochais C, Lecoutey C, Hamidouche K, Giannoni P, Gaven F, Cem E, Mignani S, Baranger K, Freret T, Bockaert J et al.. (2020)
Donecopride, a Swiss army knife with potential against Alzheimer's disease.
Br J Pharmacol, 177 (9): 1988-2005. [PMID:31881553]