ancriviroc   Click here for help

GtoPdb Ligand ID: 804

Synonyms: SCH 351125 | SCH-351125 | SCH-C
Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: Ancriviroc (SCH351125) is an orally available, small molecule antagonist of the C-C chemokine receptor type 5 (CCR5) expressed on T cells [4]. The compound was originally investigated as an anti-HIV therapeutic [4]. SCH351125-induced CCR5 blockade was investigated for action in treating rheumatoid arthritis, but with discouraging clinical trial results [6]. Other CCR5 antagonists (AZD5672 and maraviroc) have also proven ineffective in RA clinical trials [5].

There is some ambiguity in the literature and online databases as to the exact structure of ancriviroc. The structure shown here matches that in the PubChem entry linked to above, and as shown in [4], while other common representations of ancriviroc match CID 5479787.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 3
Hydrogen bond donors 0
Rotatable bonds 7
Topological polar surface area 72.08
Molecular weight 556.2
XLogP 6.4
No. Lipinski's rules broken 1
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Canonical SMILES CCON=C(c1ccc(cc1)Br)C1CCN(CC1)C1(C)CCN(CC1)C(=O)c1c(C)cc[n+](c1C)[O-]
Isomeric SMILES CCO/N=C(\c1ccc(cc1)Br)/C1CCN(CC1)C1(C)CCN(CC1)C(=O)c1c(C)cc[n+](c1C)[O-]
InChI InChI=1S/C28H37BrN4O3/c1-5-36-30-26(22-6-8-24(29)9-7-22)23-11-15-32(16-12-23)28(4)13-18-31(19-14-28)27(34)25-20(2)10-17-33(35)21(25)3/h6-10,17,23H,5,11-16,18-19H2,1-4H3/b30-26+
1. Maeda K, Das D, Ogata-Aoki H, Nakata H, Miyakawa T, Tojo Y, Norman R, Takaoka Y, Ding J, Arnold GF, Arnold E, Mitsuya H. (2006)
Structural and molecular interactions of CCR5 inhibitors with CCR5.
J Biol Chem, 281: 12688-12698. [PMID:16476734]
2. Palani A, Shapiro S, Clader JW, Greenlee WJ, Cox K, Strizki J, Endres M, Baroudy BM. (2001)
Discovery of 4-[(Z)-(4-bromophenyl)- (ethoxyimino)methyl]-1'-[(2,4-dimethyl-3- pyridinyl)carbonyl]-4'-methyl-1,4'- bipiperidine N-oxide (SCH 351125): an orally bioavailable human CCR5 antagonist for the treatment of HIV infection.
J Med Chem, 44 (21): 3339-42. [PMID:11585437]
3. Strizki JM, Tremblay C, Xu S, Wojcik L, Wagner N, Gonsiorek W, Hipkin RW, Chou CC, Pugliese-Sivo C, Xiao Y et al.. (2005)
Discovery and characterization of vicriviroc (SCH 417690), a CCR5 antagonist with potent activity against human immunodeficiency virus type 1.
Antimicrob Agents Chemother, 49 (12): 4911-9. [PMID:16304152]
4. Strizki JM, Xu S, Wagner NE, Wojcik L, Liu J, Hou Y, Endres M, Palani A, Shapiro S, Clader JW et al.. (2001)
SCH-C (SCH 351125), an orally bioavailable, small molecule antagonist of the chemokine receptor CCR5, is a potent inhibitor of HIV-1 infection in vitro and in vivo.
Proc Natl Acad Sci USA, 98 (22): 12718-23. [PMID:11606733]
5. Takeuchi T, Kameda H. (2012)
What is the future of CCR5 antagonists in rheumatoid arthritis?.
Arthritis Res Ther, 14 (2): 114. [PMID:22494450]
6. van Kuijk AW, Vergunst CE, Gerlag DM, Bresnihan B, Gomez-Reino JJ, Rouzier R, Verschueren PC, van der Leij C, van de Leij C, Maas M et al.. (2010)
CCR5 blockade in rheumatoid arthritis: a randomised, double-blind, placebo-controlled clinical trial.
Ann Rheum Dis, 69 (11): 2013-6. [PMID:20693270]