PF-04457845   Click here for help

GtoPdb Ligand ID: 6694

Synonyms: compound 23 [PMID: 21666860] | PF04457845
Compound class: Synthetic organic
Comment: PF-04457845 is a highly selective, irreversible, covalent inactivator of fatty acid amide hydrolase (FAAH) [2], that is being investigated in clinical trials. It is one example from a dense analogoue series from patents (see 'Similar Compounds' in PubChem).
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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

PF-04457845 is commercially available from our sponsors

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 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 6
Hydrogen bond donors 1
Rotatable bonds 7
Topological polar surface area 80.24
Molecular weight 455.16
XLogP 3.74
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 O=C(N1CCC(=Cc2cccc(c2)Oc2ccc(cn2)C(F)(F)F)CC1)Nc1cccnn1
Isomeric SMILES O=C(N1CCC(=Cc2cccc(c2)Oc2ccc(cn2)C(F)(F)F)CC1)Nc1cccnn1
InChI InChI=1S/C23H20F3N5O2/c24-23(25,26)18-6-7-21(27-15-18)33-19-4-1-3-17(14-19)13-16-8-11-31(12-9-16)22(32)29-20-5-2-10-28-30-20/h1-7,10,13-15H,8-9,11-12H2,(H,29,30,32)
InChI Key BATCTBJIJJEPHM-UHFFFAOYSA-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. Janero DR, Vadivel SK, Makriyannis A. (2009)
Pharmacotherapeutic modulation of the endocannabinoid signalling system in psychiatric disorders: drug-discovery strategies.
Int Rev Psychiatry, 21 (2): 122-33. [PMID:19367506]
2. Johnson DS, Stiff C, Lazerwith SE, Kesten SR, Fay LK, Morris M, Beidler D, Liimatta MB, Smith SE, Dudley DT et al.. (2011)
Discovery of PF-04457845: A Highly Potent, Orally Bioavailable, and Selective Urea FAAH Inhibitor.
ACS Med Chem Lett, 2 (2): 91-96. [PMID:21666860]
3. Pertwee RG. (2014)
Elevating endocannabinoid levels: pharmacological strategies and potential therapeutic applications.
Proc Nutr Soc, 73 (1): 96-105. [PMID:24135210]
4. Sałaga M, Sobczak M, Fichna J. (2014)
Inhibition of fatty acid amide hydrolase (FAAH) as a novel therapeutic strategy in the treatment of pain and inflammatory diseases in the gastrointestinal tract.
Eur J Pharm Sci, 52: 173-9. [PMID:24275607]
5. van Esbroeck ACM, Janssen APA, Cognetta 3rd AB, Ogasawara D, Shpak G, van der Kroeg M, Kantae V, Baggelaar MP, de Vrij FMS, Deng H et al.. (2017)
Activity-based protein profiling reveals off-target proteins of the FAAH inhibitor BIA 10-2474.
Science, 356 (6342): 1084-1087. [PMID:28596366]