AZD5672   Click here for help

GtoPdb Ligand ID: 7686

Synonyms: AZD 5672 | AZD-5672
Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: AZD5672 was an investigational small molecule antagonist of the C-C chemokine receptor type 5 (CCR5) expressed on T cells. AZD5672-induced CCR5 blockade was investigated for action in treating rheumatoid arthritis, but with discouraging clinical trial results. Other CCR5 antagonists (ancriviroc and maraviroc) have also proven ineffective in RA clinical trials [4]

The structure shown here was drawn from [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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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 0
Rotatable bonds 12
Topological polar surface area 111.83
Molecular weight 639.26
XLogP 4.32
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 CCN(C(=O)Cc1ccc(cc1)S(=O)(=O)C)C1CCN(CC1)CCC(c1cc(F)cc(c1)F)C1CCN(CC1)S(=O)(=O)C
Isomeric SMILES CCN(C(=O)Cc1ccc(cc1)S(=O)(=O)C)C1CCN(CC1)CC[C@@H](c1cc(F)cc(c1)F)C1CCN(CC1)S(=O)(=O)C
InChI InChI=1S/C31H43F2N3O5S2/c1-4-36(31(37)19-23-5-7-29(8-6-23)42(2,38)39)28-11-14-34(15-12-28)16-13-30(25-20-26(32)22-27(33)21-25)24-9-17-35(18-10-24)43(3,40)41/h5-8,20-22,24,28,30H,4,9-19H2,1-3H3/t30-/m1/s1
InChI Key QOSMEMHKXNNIGG-SSEXGKCCSA-N
References
1. Cumming JG, Tucker H, Oldfield J, Fielding C, Highton A, Faull A, Wild M, Brown D, Wells S, Shaw J. (2012)
Balancing hERG affinity and absorption in the discovery of AZD5672, an orally active CCR5 antagonist for the treatment of rheumatoid arthritis.
Bioorg Med Chem Lett, 22 (4): 1655-9. [PMID:22266038]
2. Haringman JJ, Smeets TJ, Reinders-Blankert P, Tak PP. (2006)
Chemokine and chemokine receptor expression in paired peripheral blood mononuclear cells and synovial tissue of patients with rheumatoid arthritis, osteoarthritis, and reactive arthritis.
Ann Rheum Dis, 65 (3): 294-300. [PMID:16107514]
3. Katschke Jr KJ, Rottman JB, Ruth JH, Qin S, Wu L, LaRosa G, Ponath P, Park CC, Pope RM, Koch AE. (2001)
Differential expression of chemokine receptors on peripheral blood, synovial fluid, and synovial tissue monocytes/macrophages in rheumatoid arthritis.
Arthritis Rheum, 44 (5): 1022-32. [PMID:11352233]
4. Takeuchi T, Kameda H. (2012)
What is the future of CCR5 antagonists in rheumatoid arthritis?.
Arthritis Res Ther, 14 (2): 114. [PMID:22494450]