AZD5672   

GtoPdb Ligand ID: 7686

Synonyms: AZD 5672 | AZD-5672
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].
2D Structure
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Physico-chemical Properties
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
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]