almorexant   Click here for help

GtoPdb Ligand ID: 2886

Synonyms: ACT-078573
Compound class: Synthetic organic
Comment: Almorexant (ACT-078573) is an investigational, oral, dual orexin receptor antagonist (DORA) [1]. Development of ACT-078573 was ceased in 2011, apparently because of the compound's side-effect profile.
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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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Click here for structure editor
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 CDK toolkit. 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 3
Hydrogen bond donors 1
Rotatable bonds 10
Topological polar surface area 50.8
Molecular weight 512.23
XLogP 5.18
No. Lipinski's rules broken 1
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.

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Canonical SMILES CNC(=O)C(N1CCc2c(C1CCc1ccc(cc1)C(F)(F)F)cc(c(c2)OC)OC)c1ccccc1
Isomeric SMILES CNC(=O)[C@H](N1CCc2c([C@@H]1CCc1ccc(cc1)C(F)(F)F)cc(c(c2)OC)OC)c1ccccc1
InChI InChI=1S/C29H31F3N2O3/c1-33-28(35)27(20-7-5-4-6-8-20)34-16-15-21-17-25(36-2)26(37-3)18-23(21)24(34)14-11-19-9-12-22(13-10-19)29(30,31)32/h4-10,12-13,17-18,24,27H,11,14-16H2,1-3H3,(H,33,35)/t24-,27+/m0/s1
InChI Key DKMACHNQISHMDN-RPLLCQBOSA-N
References
1. Brisbare-Roch C, Dingemanse J, Koberstein R, Hoever P, Aissaoui H, Flores S, Mueller C, Nayler O, van Gerven J, de Haas SL, Hess P, Qiu C, Buchmann S, Scherz M, Weller T, Fischli W, Clozel M, Jenck F. (2007)
Promotion of sleep by targeting the orexin system in rats, dogs and humans.
Nat Med, 13 (2): 150-5. [PMID:17259994]
2. Callander GE, Olorunda M, Monna D, Schuepbach E, Langenegger D, Betschart C, Hintermann S, Behnke D, Cotesta S, Fendt M et al.. (2013)
Kinetic properties of "dual" orexin receptor antagonists at OX1R and OX2R orexin receptors.
Front Neurosci, 7: 230. [PMID:24376396]
3. Malherbe P, Borroni E, Gobbi L, Knust H, Nettekoven M, Pinard E, Roche O, Rogers-Evans M, Wettstein JG, Moreau JL. (2009)
Biochemical and behavioural characterization of EMPA, a novel high-affinity, selective antagonist for the OX(2) receptor.
Br J Pharmacol, 156 (8): 1326-41. [PMID:19751316]
4. Malherbe P, Borroni E, Pinard E, Wettstein JG, Knoflach F. (2009)
Biochemical and electrophysiological characterization of almorexant, a dual orexin 1 receptor (OX1)/orexin 2 receptor (OX2) antagonist: comparison with selective OX1 and OX2 antagonists.
Mol Pharmacol, 76 (3): 618-31. [PMID:19542319]
5. Malherbe P, Roche O, Marcuz A, Kratzeisen C, Wettstein JG, Bissantz C. (2010)
Mapping the binding pocket of dual antagonist almorexant to human orexin 1 and orexin 2 receptors: comparison with the selective OX1 antagonist SB-674042 and the selective OX2 antagonist N-ethyl-2-[(6-methoxy-pyridin-3-yl)-(toluene-2-sulfonyl)-amino]-N-pyridin-3-ylmethyl-acetamide (EMPA).
Mol Pharmacol, 78 (1): 81-93. [PMID:20404073]
6. Treiber A, de Kanter R, Roch C, Gatfield J, Boss C, von Raumer M, Schindelholz B, Muehlan C, van Gerven J, Jenck F. (2017)
The Use of Physiology-Based Pharmacokinetic and Pharmacodynamic Modeling in the Discovery of the Dual Orexin Receptor Antagonist ACT-541468.
J Pharmacol Exp Ther, 362 (3): 489-503. [PMID:28663311]