PF-04905428   Click here for help

GtoPdb Ligand ID: 9062

Synonyms: CE-224,535 | CE-224535 | compound 3 [PMID: 21782426] | compound 33 [PMID: 21565499]
Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: PF-04905428 is an investigational purinergic receptor 2 (P2X7) antagonist [2,4], with potential antiinflammatory action in various conditions such as arthritis, allergies, asthma, COPD, autoimmune diseases and other disorders.. PF-04905428 is one of the compounds claimed in patent US6974812 [1].
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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 8
Hydrogen bond donors 3
Rotatable bonds 9
Topological polar surface area 135.16
Molecular weight 480.18
XLogP 2.51
No. Lipinski's rules broken 0
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 COCC(Cn1c(=O)cnn(c1=O)c1ccc(c(c1)C(=O)NCC1(O)CCCCCC1)Cl)O
Isomeric SMILES COC[C@@H](Cn1c(=O)cnn(c1=O)c1ccc(c(c1)C(=O)NCC1(O)CCCCCC1)Cl)O
InChI InChI=1S/C22H29ClN4O6/c1-33-13-16(28)12-26-19(29)11-25-27(21(26)31)15-6-7-18(23)17(10-15)20(30)24-14-22(32)8-4-2-3-5-9-22/h6-7,10-11,16,28,32H,2-5,8-9,12-14H2,1H3,(H,24,30)/t16-/m1/s1
InChI Key FUCKCIVGBCBZNP-MRXNPFEDSA-N
References
1. Dombroski MA, Duplantier AJ. (2005)
Benzamide inhibitors of the P2X7 receptor.
Patent number: US6974812 B2. Assignee: Pfizer Inc.. Priority date: 31/12/2002. Publication date: 13/12/2005.
2. Duplantier AJ, Dombroski MA, Subramanyam C, Beaulieu AM, Chang SP, Gabel CA, Jordan C, Kalgutkar AS, Kraus KG, Labasi JM et al.. (2011)
Optimization of the physicochemical and pharmacokinetic attributes in a 6-azauracil series of P2X7 receptor antagonists leading to the discovery of the clinical candidate CE-224,535.
Bioorg Med Chem Lett, 21 (12): 3708-11. [PMID:21565499]
3. Stock TC, Bloom BJ, Wei N, Ishaq S, Park W, Wang X, Gupta P, Mebus CA. (2012)
Efficacy and safety of CE-224,535, an antagonist of P2X7 receptor, in treatment of patients with rheumatoid arthritis inadequately controlled by methotrexate.
J Rheumatol, 39 (4): 720-7. [PMID:22382341]
4. Subramanyam C, Duplantier AJ, Dombroski MA, Chang SP, Gabel CA, Whitney-Pickett C, Perregaux DG, Labasi JM, Yoon K, Shepard RM et al.. (2011)
Discovery, synthesis and SAR of azinyl- and azolylbenzamides antagonists of the P2X₇ receptor.
Bioorg Med Chem Lett, 21 (18): 5475-9. [PMID:21782426]