AQW051   Click here for help

GtoPdb Ligand ID: 7371

Synonyms: AQW-051 | VQW 765 | VQW-765 | VQW765
Compound class: Synthetic organic
Comment: AQW 051 is an α7 nicotinic acetylcholine receptor (nAChR) partial agonist from Novartis for the oral treatment of cognitive deficits in schizophrenia, Alzheimer's, and Parkinson's diseases [1,3]. Structure first disclosed at March 2014 ACS meeting. The (3S) version is CID 71553840. The compound was later re-named to VQW-765 (Vanda Pharmaceuticals).
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species
2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 2
Hydrogen bond donors 0
Rotatable bonds 3
Topological polar surface area 25.36
Molecular weight 294.17
XLogP 3.57
No. Lipinski's rules broken 0

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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Canonical SMILES Cc1ccc(cc1)c1ccc(cn1)OC1CN2CCC1CC2
Isomeric SMILES Cc1ccc(cc1)c1ccc(cn1)O[C@H]1CN2CCC1CC2
InChI InChI=1S/C19H22N2O/c1-14-2-4-15(5-3-14)18-7-6-17(12-20-18)22-19-13-21-10-8-16(19)9-11-21/h2-7,12,16,19H,8-11,13H2,1H3/t19-/m0/s1
InChI Key NPDLTEZXGWRMLQ-IBGZPJMESA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
References
1. Di Paolo T, Grégoire L, Feuerbach D, Elbast W, Weiss M, Gomez-Mancilla B. (2014)
AQW051, a novel and selective nicotinic acetylcholine receptor α7 partial agonist, reduces l-Dopa-induced dyskinesias and extends the duration of l-Dopa effects in parkinsonian monkeys.
Parkinsonism Relat Disord, 20 (11): 1119-23. [PMID:25172125]
2. Di Paolo, Thérèse et. al. (2011)
Use of nicotinic acetylcholine receptor alpha 7 activators.
Patent number: WO2011036167. Assignee: Novartis. Priority date: 22/09/2009. Publication date: 31/03/2011.
3. Feuerbach D, Pezous N, Weiss M, Shakeri-Nejad K, Lingenhoehl K, Hoyer D, Hurth K, Bilbe G, Pryce CR, McAllister K et al.. (2015)
AQW051, a novel, potent and selective α7 nicotinic ACh receptor partial agonist: pharmacological characterization and phase I evaluation.
Br J Pharmacol, 172 (5): 1292-304. [PMID:25363835]
4. Hurth K, et. al. 
MEDI 222: Identification of AQW051, an alpha7 nicotinic acetylcholine receptor partial agonist for the treatment of cognitive impairment associated with schizophrenia.
Accessed on 06/04/2014. Modified on 06/04/2014. ACS Med Chem Meeting Abstracts, March 2014, http://www.acsmedchem.org/mediabstracts2014.pdf
5. Trenkwalder C, Berg D, Rascol O, Eggert K, Ceballos-Baumann A, Corvol JC, Storch A, Zhang L, Azulay JP, Broussolle E et al.. (2016)
A Placebo-Controlled Trial of AQW051 in Patients With Moderate to Severe Levodopa-Induced Dyskinesia.
Mov Disord, 31 (7): 1049-54. [PMID:26990766]