1,053
Views
87
CrossRef citations to date
0
Altmetric
Review

Chemokine receptor antagonists: Part 1

&
Pages 39-58 | Published online: 05 Jan 2009

Bibliography

  • Zlotnik A, Yoshie O. Chemokines: a new classification system and their role in immunity. Immunity 2000;12:121-7
  • van Creveld S, Paulssen MM. Significance of clotting factors in blood-platelets, in normal and pathological conditions. Lancet 1951;2:242-4
  • Murphy PM, Baggiolini M, Charo IF, et al. International union of pharmacology. XXII. Nomenclature for chemokine receptors. Pharmacol Rev 2000;52:145-76
  • Fredriksson R, Lagerstrom MC, Lundin LG, Schioth HB. The G-protein-coupled receptors in the human genome form five main families. Phylogenetic analysis, paralogon groups, and fingerprints. Mol Pharmacol 2003;63:1256-72
  • Baggiolini M. Chemokines and leukocyte traffic. Nature 1998;392:565-8
  • Gerard C, Rollins BJ. Chemokines and disease. Nat Immunol 2001;2:108-15
  • Feng Y, Broder CC, Kennedy PE, Berger EA. HIV-1 entry cofactor: functional cDNA cloning of a seven-transmembrane, G protein-coupled receptor. Science 1996;272:872-7
  • Doranz BJ, Rucker J, Yi YJ, et al. A dual-tropic primary HIV-1 isolate that uses fusin and the b-chemokine receptors CKR-5, CKR-3, and CKR-2b as fusion cofactors. Cell 1996;85:1149-58
  • Ribeiro S, Horuk R. Chemokine receptor antagonists from the bench to the clinic. In: Hannan A, Engelhardt B, Editors, Weinheim: Wiley-VCH; 2005
  • Ribeiro S, Horuk R. The clinical potential of chemokine receptor antagonists. Pharmacol Ther 2005;107:44-58
  • MacArthur RD, Novak RM. Reviews of anti-infective agents: maraviroc: the first of a new class of antiretroviral agents. Clin Infect Dis 2008;47:236-41
  • Schwarz MK, Wells TNC. Recent developments in modulating chemokine networks. Expert Opin Ther Pat 1999;9:1471-89
  • Pease JE, Williams TJ. The attraction of chemokines as a target for specific anti-inflammatory therapy. Br J Pharmacol 2006;147(Suppl 1):S212-21
  • Neote K, DiGregorio D, Mak JY, et al. Molecular cloning, functional expression, and signaling characteristics of a C-C chemokine receptor. Cell 1993;72:415-25
  • Gao JL, Kuhns DB, Tiffany HL, et al. Structure and functional expression of the human macrophage inflammatory protein 1 alpha/RANTES receptor. J Exp Med 1993;177:1421-7
  • Weber C, Weber KS, Klier C, et al. Specialized roles of the chemokine receptors CCR1 and CCR5 in the recruitment of monocytes and T(H)1-like/CD45RO(+) T cells. Blood 2001;97:1144-6
  • Broxmeyer HE, Cooper S, Hangoc G, et al. Dominant Myelopoietic Effector Functions Mediated by Chemokine Receptor CCR1. J Exp Med 1999;189:1987-92
  • Gao JL, Wynn TA, Chang Y, et al. Impaired host defense, hematopoiesis, granulomatous inflammation and type 1-type 2 cytokine balance in mice lacking CC chemokine receptor 1. J Exp Med 1997;185:1959-68
  • Gerard C, Frossard JL, Bhatia M, et al. Targeted disruption of the beta-chemokine receptor CCR1 protects against pancreatitis-associated lung injury. J Clin Invest 1997;100:2022-7
  • Barnes DA, Tse J, Kaufhold M, et al. Polyclonal antibody directed against human RANTES ameliorates disease in the Lewis rat adjuvant-induced arthritis model. J Clin Invest 1998;101:2910-9
  • Trebst C, Sorensen TL, Kivisakk P, et al. CCR1+/CCR5+ mononuclear phagocytes accumulate in the central nervous system of patients with multiple sclerosis. Am J Pathol 2001;159:1701-10
  • Rottman JB, Slavin AJ, Silva R, et al. Leukocyte recruitment during onset of experimental allergic encephalomyelitis is CCR1 dependent. Eur J Immunol 2000;30:2372-7
  • Pattison JM, Nelson PJ, Huie P, et al. RANTES chemokine expression in transplant-associated accelerated atherosclerosis. J Heart Lung Transplant 1996;15:1194-9
  • Gao W, Topham PS, King JA, et al. Targeting of the chemokine receptor CCR1 suppresses development of acute and chronic cardiac allograft rejection. J Clin Invest 2000;105:35-44
  • Sabroe I, Hartnell A, Jopling LA, et al. Differential Regulation of Eosinophil Chemokine Signaling Via CCR3 and Non-CCR3 Pathways. J Immunol 1999;162:2946-55
  • Toda M, Dawson M, Nakamura T, et al. Impact of Engagement of FcepsilonRI and CC chemokine receptor 1 on mast cell activation and motility. J Biol Chem 2004;279:48443-8
  • Liang M, Mallari C, Rosser M, et al. Identification and characterization of a potent, selective, and orally active antagonist of the CC chemokine receptor-1. J Biol Chem 2000;275:19000-8
  • Horuk R, Clayberger C, Krensky AM, et al. A non-peptide functional antagonist of the CCR1 chemokine receptor is effective in rat heart transplant rejection. J Biol Chem 2001;276:4199-204
  • Anders HJ, Vielhauer V, Frink M, et al. A chemokine receptor CCR-1 antagonist reduces renal fibrosis after unilateral ureter ligation. J Clin Invest 2002;109:251-9
  • Menu E, De Leenheer E, De Raeve H, et al. Role of CCR1 and CCR5 in homing and growth of multiple myeloma and in the development of osteolytic lesions: a study in the 5TMM model. Clin Exp Metastasis 2006;23:291-300
  • Zipp F, Hartung HP, Hillert J, et al. Blockade of chemokine signaling in patients with multiple sclerosis. Neurology 2006;67:1880-3
  • Gladue RP, Tylaska LA, Brissette WH, et al. CP-481,715: A potent and selective CCR1 antagonist with potential therapeutic implications for inflammatory diseases. J Biol Chem 2003;278:40473-80
  • Brown MF, Avery M, Brissette WH, et al. Novel CCR1 antagonists with improved metabolic stability. Bioorg Med Chem Lett 2004;14:2175-9
  • Kath JC, Brissette WH, Brown MF, et al. Potent small molecule CCR1 antagonists. Bioorg Med Chem Lett 2004;14:2169-73
  • Kath JC, DiRico AP, Gladue RP, et al. The discovery of structurally novel CCR1 antagonists derived from a hydroxyethylene peptide isostere template. Bioorg Med Chem Lett 2004;14:2163-7
  • Gladue RP, Cole SH, Roach ML, et al. The human specific CCR1 antagonist CP-481,715 inhibits cell infiltration and inflammatory responses in human CCR1 transgenic mice. J Immunol 2006;176:3141-8
  • Brown MF, Bahnck KB, Blumberg LC, et al. Piperazinyl CCR1 antagonists–optimization of human liver microsome stability. Bioorg Med Chem Lett 2007;17:3109-12
  • Brown MF, Kath JC, Poss CS. Heteroaryl-hexanoic acid amide derivatives, their preparation and their use as selective inhibitors of MIP-1-alpha binding to its CCR1 receptor. WO199838167; 1998
  • Brown MF, Poss CS. Heterocyclic amide derivatives useful as inhibitors of MIP-1alpha binding to CCR1 receptors. WO200157023; 2001
  • Brown MF, Poss CS. Quinoxalinyl amide derivatives. US6548671; 2003
  • Blumberg LC, Brown MF, Gladue RP, et al. Piperazine derivatives. US6649611; 2003
  • Kath JC, Brown MF, Poss CS. Dihydroxyhexanoic acid derivatives. US6673801; 2004
  • Hayward MA, Sulfonic acid derivatives. US6974817; 2005
  • Gladue RP, Zwillich SH, Clucas AT, Brown MF. CCR1 antagonists for the treatment of autoimmune diseases. Curr Opin Investig Drugs 2004;5:499-504
  • Luly J, Nakasuto Y, Oshima E. Chemokine receptor antagonists and methods of use thereof. US6288083; 2001
  • Luly J, Nakasuto Y, Oshima E, et al. Chemokine receptor antagonists and methods of use thereof. US6509346; 2003
  • Luly J, Nakasuto Y, Oshima E, et al. Chemokine receptor antagonists and methods of use thereof. US6503926; 2003
  • Carson KG, Harriman GCB. CCR1 antagonists and methods of use therefor. US20040106639; 2004
  • Carson KG, Harriman GCB. CCR1 antagonists and methods of use therefor. US20050288319; 2005
  • Luly J, Nakasuto Y, Oshima E, et al. Chemokine receptor antagonists and methods of use thereof. US7271176; 2007
  • IDdb. MLN-3897 Update. The Investigational Drugs Database Drug Report, 2004. Available from: http://www.iddb3.com/iddb3/iddb3_2/reports.display?id=37473&template=Drug&i_query_id=4471271
  • Hesselgesser J, Ng HP, Liang M, et al. Identification and characterization of small molecule functional antagonists of the ccr1 chemokine receptor. J Biol Chem 1998;273:15687-92
  • Ng HP, May K, Bauman JG, et al. Discovery of novel non-peptide CCR1 receptor antagonists. J Med Chem 1999;42:4680-94
  • Vallet S, Raje N, Ishitsuka K, et al. MLN3897, a novel CCR1 inhibitor, impairs osteoclastogenesis and inhibits the interaction of multiple myeloma cells and osteoclasts. Blood 2007;110:3744-52
  • Vann L. End of 2007 brings Extra Activity. Autoimmune Drug Focus 2007;37:1
  • McMaster BE, Anti-inflammatory compositions and methods of use. US6727241; 2003
  • Pennell AMK, Aggen JB, Wright JJK, et al. 1-Aryl-4-substituted piperazines derivatives for use as CCR1 antagonists for the treatment of inflammation and immune disorders. WO2003105853; 2003
  • Pennell AMK, Aggen JB, Wright JJK, et al. Substituted piperazines. US7157464; 2007
  • Zhang P, Pennell AMK, W C, et al. Piperidine derivatives and methods of use. US20070088036; 2007
  • Zhang P, Pennell AMK, W C, et al. Piperidine derivatives and methods of use. US20070093467; 2007
  • Zhang P, Pennell AMK, Wright JJK, et al. Monocyclic and bicyclic compounds and methods of use. US20070066583; 2007
  • Zhang P, Pennell AMK, Wright JJK, et al. Azaindazole compounds and methods of use. US20070010524; 2007
  • Zhang P, Pennell AMK, Wright JJK, et al. Azaindazole compounds and methods of use. US20070010523; 2007
  • Naya A, Owada Y, Saeki T, et al. Chemokine receptor antagonists. US6140338; 1999
  • Naya A, Sagara Y, Ohwaki K, et al. Design, synthesis, and discovery of a novel CCR1 antagonist. J Med Chem 2001;44:1429-35
  • Naya A, Kobayashi K, Ishikawa M, et al. Discovery of a novel CCR3 selective antagonist. Bioorg Med Chem Lett 2001;11:1219-23
  • Saeki T, Naya A. CCR1 chemokine receptor antagonist. Curr Pharm Des 2003;9:1201-8
  • Xie YF, Sircar I, Lake K, et al. Identification of novel series of human CCR1 antagonists. Bioorg Med Chem Lett 2008;18:2215-21
  • Xie YF, Lake K, Ligsay K, et al. Structure-activity relationships of novel, highly potent, selective, and orally active CCR1 antagonists. Bioorg Med Chem Lett 2007;17:3367-72
  • Bollbuck B, Eder J, Heng R, et al. 1-(4-benzyl-piperazin-1-yl)- 3-phenyl-propenone derivatives. WO2004037796; 2004
  • Revesz L, Bollbuck B, Buhl T, et al. Novel CCR1 antagonists with oral activity in the mouse collagen induced arthritis. Bioorg Med Chem Lett 2005;15:5160-4
  • Charo IF, Myers SJ, Herman A, et al. Molecular cloning and functional expression of two monocyte chemoattractant protein 1 receptors reveals alternative splicing of the carboxyl-terminal tails. Proc Natl Acad Sci USA 1994;91:2752-6
  • Hancock WW, Gao W, Faia KL, Csizmadia V. Chemokines and their receptors in allograft rejection. Curr Opin Immunol 2000;12:511-6
  • Szekanecz Z, Szucs G, Szanto S, Koch AE. Chemokines in rheumatic diseases. Curr Drug Targets 2006;7:91-102
  • Charo IF, Ransohoff RM. The many roles of chemokines and chemokine receptors in inflammation. N Engl J Med 2006;354:610-21
  • Taylor PC, Peters AM, Paleolog E, et al. Reduction of chemokine levels and leukocyte traffic to joints by tumor necrosis factor alpha blockade in patients with rheumatoid arthritis. Arthritis Rheum 2000;43:38-47
  • Min DJ, Cho ML, Lee SH, et al. Augmented production of chemokines by the interaction of type II collagen-reactive T cells with rheumatoid synovial fibroblasts. Arthritis Rheum 2004;50:1146-55
  • Katschke KJ Jr, Rottman JB, Ruth JH, et al. Differential expression of chemokine receptors on peripheral blood, synovial fluid, and synovial tissue monocytes/macrophages in rheumatoid arthritis. Arthritis Rheum 2001;44:1022-32
  • Ellingsen T, Hornung N, Moller BK, et al. Differential effect of methotrexate on the increased CCR2 density on circulating CD4 T lymphocytes and monocytes in active chronic rheumatoid arthritis, with a down regulation only on monocytes in responders. Ann Rheum Dis 2007;66:151-7
  • Karpus WJ, Kennedy KJ. MIP-1alpha and MCP-1 differentially regulate acute and relapsing autoimmune encephalomyelitis as well as Th1/Th2 lymphocyte differentiation. J Leukoc Biol 1997;62:681-7
  • Gosling J, Slaymaker S, Gu L, et al. MCP-1 deficiency reduces susceptibility to atherosclerosis in mice that overexpress human apolipoprotein B. J Clin Invest 1999;103:773-8
  • Boring L, Gosling J, Cleary M, Charo IF. Decreased lesion formation in CCR2-/- mice reveals a role for chemokines in the initiation of atherosclerosis. Nature 1998;394:894-7
  • Butora G, Jiao R, Parsons WH, et al. 3-Amino-1-alkyl-cyclopentane carboxamides as small molecule antagonists of the human and murine CC chemokine receptor 2. Bioorg Med Chem Lett 2007;17:3636-41
  • Butora G, Morriello GJ, Kothandaraman S, et al. 4-Amino-2-alkyl-butyramides as small molecule CCR2 antagonists with favorable pharmacokinetic properties. Bioorg Med Chem Lett 2006;16:4715-22
  • Yang L, Butora G, Jiao RX, et al. Discovery of 3-piperidinyl-1-cyclopentanecarboxamide as a novel scaffold for highly potent CC chemokine receptor 2 antagonists. J Med Chem 2007;50:2609-11
  • Yang L, Zhou C, Guo L, et al. Discovery of 3,5-bis(trifluoromethyl)benzyl L-arylglycinamide based potent CCR2 antagonists. Bioorg Med Chem Lett 2006;16:3735-9
  • Pinkerton AB, Huang D, Cube RV, et al. Diaryl substituted pyrazoles as potent CCR2 receptor antagonists. Bioorg Med Chem Lett 2007;17:807-13
  • Pasternak A, Goble SD, Doss GA, et al. Conformational studies of 3-amino-1-alkyl-cyclopentane carboxamide CCR2 antagonists leading to new spirocyclic antagonists. Bioorg Med Chem Lett 2008;18:1374-7
  • Pasternak A, Goble SD, Vicario PP, et al. Potent heteroarylpiperidine and carboxyphenylpiperidine 1-alkyl-cyclopentane carboxamide CCR2 antagonists. Bioorg Med Chem Lett 2008;18:994-8
  • Pasternak A, Marino D, Vicario PP, et al. Novel, orally bioavailable gamma-aminoamide CC chemokine receptor 2 (CCR2) antagonists. J Med Chem 2006;49:4801-4
  • Yang L, Butora G, Parsons WH, Pasternak A. Cyclopentyl modulators of chemokine receptor activity. US20050049222; 2005
  • Jiao R, Butora G, Goble SD, et al. Tetrahydropyranyl cyclopentyl tetrahydropyridopyridine modulators of chemokine receptor activity. US20050107422; 2005
  • Abbadie C, Lindia JA, Wang H. CCR2 antagonists for treatment of neuropathic pain. US20060205761; 2006
  • DeMartino J, Akiyama T, Struthers M, et al. Tetrahydropyranyl cyclopentyl tetrahydropyridopyridine modulators of chemokine receptor activity. US20060030582; 2006
  • Butora G, Pasternak A, Yang L, Zhou C, Gamma-aminoamide modulators of chemokine receptor activity. US7247725; 2007
  • Yang L, Mills SG, Zhou C, et al. 2,6-disubstituted piperidines as modulators. US7410961; 2008
  • Goble SD, Pasternak A, Mills SG, et al. Tetrahydropyranyl cyclopentyl heterocyclic amide modulators of chemokine receptor activity. US7393844; 2008
  • Forrest MLJ, Demartino JA, Flicker MR, et al. Drug Combination Therapy and Pharmaceutical Compositions for Treating Inflammatory Disorders. US20080194548; 2008
  • Yang L, Jiao RX, Moyes C, et al. The discovery of MK-0812, a potent and selective CCR2 antagonist. American Chemical Society Meeting. Chicago: 2007. Available from: www.acsmedchem.org/mediabstracts2007.pdf
  • Beaulieu A, Hasler F, Martin Mola E, et al. The efficacy and safety of a CCR2 receptor antagonist in the treatment of rheumatoid arthritis (RA). Ann Rheum Dis 2006;65(Suppl II):175. Available from: http://www.abstracts2view.com/eular/search.php?search=do&intMaxHits= 10&where[]=&andornot[]=&query= CCR2+antagonist.
  • Braddock M. 11th Annual Inflammatory and Immune Diseases Drug Discovery and Development Summit 12-13 March 2007, San Francisco, USA. Expert Opin Investig Drugs 2007;16:909-17
  • Braddock M. Advances in Anti-Inflammatory Therapeutics: 20-21 November 2006, London, UK. Expert Opin Investig Drugs 2007;16:257-61
  • Imai M, Shiota T, Kataoka K, et al. Small molecule inhibitors of the CCR2b receptor. Part 1: Discovery and optimization of homopiperazine derivatives. Bioorg Med Chem Lett 2004;14:5407-11
  • Moree WJ, Kataoka K, Ramirez-Weinhouse MM, et al. Small molecule antagonists of the CCR2b receptor. Part 2: Discovery process and initial structure-activity relationships of diamine derivatives. Bioorg Med Chem Lett 2004;14:5413-6
  • Moree WJ, Kataoka K, Ramirez-Weinhouse MM, et al. Potent antagonists of the CCR2b receptor. Part 3: SAR of the (R)-3-aminopyrrolidine series. Bioorg Med Chem Lett 2008;18:1869-73
  • Charvat TT, Hu C, Jin J, et al. Triazolyl pyridyl benzenesulfonamides. US20080039504; 2008
  • Available from: http://www.chemocentryx.com/product/CCR2.html.
  • Mirzadegan T, Diehl F, Ebi B, et al. Identification of the binding site for a novel class of CCR2b chemokine receptor antagonists: binding to a common chemokine receptor motif within the helical bundle. J Biol Chem 2000;275:25562-71
  • Berkhout TA, Blaney FE, Bridges AM, et al. CCR2: characterization of the antagonist binding site from a combined receptor modeling/mutagenesis approach. J Med Chem 2003;46:4070-86
  • Cherney RJ, Mo R, Meyer DT, et al. Discovery of disubstituted cyclohexanes as a new class of CC chemokine receptor 2 antagonists. J Med Chem 2008;51:721-4
  • Cherney RJ, Nelson DJ, Lo YC, et al. Synthesis and evaluation of cis-3,4-disubstituted piperidines as potent CC chemokine receptor 2 (CCR2) antagonists. Bioorg Med Chem Lett 2008;18:5063-5
  • Clark RD, Caroon JM, Kluge AF, et al. Synthesis and antihypertensive activity of 4′-substituted spiro[4H-3,1-benzoxazine-4,4′-piperidin]-2(1H)-ones. J Med Chem 1983;26:657-61
  • Strader CD, Fong TM, Tota MR, et al. Structure and function of G protein-coupled receptors. Annu Rev Biochem 1994;63:101-32
  • Xue C, Feng H, Cao G, et al. 3-Cycloalkylaminopyrrolidine derivatives as modulators of chemokine receptors. WO2004050024; 2004
  • Brodmerkel CM, Huber R, Covington M, et al. Discovery and pharmacological characterization of a novel rodent-active CCR2 antagonist, INCB3344. J Immunol 2005;175:5370-8
  • Xue C, Metcalf BW, Han AQ, et al. Salts of N-[2-({(3R)-1-[trans-4-hydroxy-4-(6-methoxypyridin-3-yl)-cyclohexyl]pyrrolidin-3-yl}amino)-2-oxoethyl]-3-(trifluoromethyl)benzamide. US20060111404; 2006
  • Xue C, Zheng C, Cao G, et al. 3-(4-heteroarylcyclohexylamino)cyclopentanecarboxamides as modulators of chemokine receptors. US7307086; 2007
  • Forbes IT, Cooper DG, Dodds EK, et al. CCR2B receptor antagonists: conversion of a weak HTS hit to a potent lead compound. Bioorg Med Chem Lett 2000;10:1803-6
  • Witherington J, Bordas V, Cooper DG, et al. Conformationally restricted indolopiperidine derivatives as potent CCR2B receptor antagonists. Bioorg Med Chem Lett 2001;11:2177-80
  • Van Lomen G, Doyon J, Coesemans E, et al. 2-Mercaptoimidazoles, a new class of potent CCR2 antagonists. Bioorg Med Chem Lett 2005;15:497-500
  • Lagu B, Gerchak C, Pan M, et al. Potent and selective CC-chemokine receptor-2 (CCR2) antagonists as a potential treatment for asthma. Bioorg Med Chem Lett 2007;17:4382-6
  • Xia M, Hou C, Demong D, et al. Substituted dipiperidine alcohols as potent CCR2 antagonists. Bioorg Med Chem Lett 2008;18:3562-4
  • Xia M, Hou C, DeMong DE, et al. Synthesis, structure-activity relationship and in vivo antiinflammatory efficacy of substituted dipiperidines as CCR2 antagonists. J Med Chem 2007;50:5561-3
  • Xia M, Hou C, Pollack S, et al. Synthesis and biological evaluation of phenyl piperidine derivatives as CCR2 antagonists. Bioorg Med Chem Lett 2007;17:5964-8
  • Kettle JG, Faull AW, Barker AJ, et al. N-Benzylindole-2-carboxylic acids: potent functional antagonists of the CCR2b chemokine receptor. Bioorg Med Chem Lett 2004;14:405-8
  • Ponath PD, Qin S, Post TW, et al. Molecular cloning and characterization of a human eotaxin receptor expressed selectively on eosinophils. J Exp Med 1996;183:2437-48
  • Sallusto F, Mackay CR, Lanzavecchia A. Selective expression of the eotaxin receptor CCR3 by human T helper 2 cells. Science 1997;277:2005-7
  • Uguccioni M, Mackay CR, Ochensberger B, et al. High expression of the chemokine receptor CCR3 in human blood basophils. Role in activation by eotaxin, MCP-4, and other chemokines. J Clin Invest 1997;100:1137-43
  • Romagnani P, De Paulis A, Beltrame C, et al. Tryptase-chymase double-positive human mast cells express the eotaxin receptor CCR3 and are attracted by CCR3-binding chemokines. Am J Pathol 1999;155:1195-204
  • Fulkerson PC, Fischetti CA, McBride ML, et al. A central regulatory role for eosinophils and the eotaxin/CCR3 axis in chronic experimental allergic airway inflammation. Proc Natl Acad Sci USA 2006;103:16418-23
  • Sabroe I, Peck MJ, Van Keulen BJ, et al. A Small Molecule Antagonist of Chemokine Receptors CCR1 and CCR3. Potent inhibition of eosinophil function and CCR3-mediated HIV-1 entry. J Biol Chem 2000;275:25985-92
  • de Mendonca FL, da Fonseca PC, Phillips RM, et al. Site-directed mutagenesis of CC chemokine receptor 1 reveals the mechanism of action of UCB 35625, a small molecule chemokine receptor antagonist. J Biol Chem 2005;280:4808-16
  • Wise EL, Duchesnes C, Da Fonseca PC, et al. Small molecule receptor agonists and antagonists of CCR3 provide insight into mechanisms of chemokine receptor activation. J Biol Chem 2007;282:27935-43
  • Pegurier C, Collart P, Danhaive P, et al. Pyrazolone methylamino piperidine derivatives as novel CCR3 antagonists. Bioorg Med Chem Lett 2007;17:4228-31
  • White JR, Lee JM, Dede K, et al. Identification of potent, selective non-peptide CC chemokine receptor-3 antagonist that inhibits eotaxin-, eotaxin-2-, and monocyte chemotactic protein-4-induced eosinophil migration. J Biol Chem 2000;275:36626-31
  • Dhanak D, Christmann LT, Darcy MG, et al. Discovery of potent and selective phenylalanine derived CCR3 antagonists. Part 1. Bioorg Med Chem Lett 2001;11:1441-4
  • Dhanak D, Christmann LT, Darcy MG, et al. Discovery of potent and selective phenylalanine derived CCR3 receptor antagonists. Part 2. Bioorg Med Chem Lett 2001;11:1445-50
  • Varnes JG, Gardner DS, Santella JB 3rd, et al. Discovery of N-propylurea 3-benzylpiperidines as selective CC chemokine receptor-3 (CCR3) antagonists. Bioorg Med Chem Lett 2004;14:1645-9
  • De Lucca GV, Kim UT, Vargo BJ, et al. Discovery of CC chemokine receptor-3 (CCR3) antagonists with picomolar potency. J Med Chem 2005;48:2194-211
  • Pruitt JR, Batt DG, Wacker DA, et al. CC chemokine receptor-3 (CCR3) antagonists: improving the selectivity of DPC168 by reducing central ring lipophilicity. Bioorg Med Chem Lett 2007;17:2992-7
  • Sato I, Morihira K, Inami H, et al. Synthesis and structure-activity relationships of N-{1-[(6-fluoro-2-naphthyl)methyl]piperidin-4-yl}benzamide derivatives as novel CCR3 antagonists. Bioorg Med Chem 2008;16:144-56
  • Sato I, Morihira K, Inami H, et al. Design and synthesis of 6-fluoro-2-naphthyl derivatives as novel CCR3 antagonists with reduced CYP2D6 inhibition. Bioorg Med Chem 2008;16:8607-18
  • Suzuki K, Morokata T, Morihira K, et al. In vitro and in vivo characterization of a novel CCR3 antagonist, YM-344031. Biochem Biophys Res Commun 2006;339:1217-23
  • Morokata T, Suzuki K, Masunaga Y, et al. A novel, selective, and orally available antagonist for CC chemokine receptor 3. J Pharmacol Exp Ther 2006;317:244-50
  • Warrior U, McKeegan EM, Rottinghaus SM, et al. Identification and characterization of novel antagonists of the CCR3 receptor. J Biomol Screen 2003;8:324-31
  • Ting PC, Lee JF, Wu J, et al. The synthesis of substituted bipiperidine amide compounds as CCR3 antagonists. Bioorg Med Chem Lett 2005;15:1375-8
  • Ting PC, Umland SP, Aslanian R, et al. The synthesis of substituted bipiperidine amide compounds as CCR3 ligands: antagonists versus agonists. Bioorg Med Chem Lett 2005;15:3020-3
  • Naya A, Kobayashi K, Ishikawa M, et al. Structure-Activity Relationships of 2-(Benzothiazolylthio)acetamide Class of CCR3 Selective Antagonist. Chem Pharm Bull (Tokyo) 2003;51:697-701
  • Murdoch RD. Oral presentation, 4th James Black Conference, The Challenges of Drug Discovery & Development. University of Hertfordshire, 2006
  • Fryer AD, Stein LH, Nie Z, et al. Neuronal eotaxin and the effects of CCR3 antagonist on airway hyperreactivity and M2 receptor dysfunction. J Clin Invest 2006;116:228-36
  • Pilette C, Francis JN, Till SJ, Durham SR. CCR4 ligands are up-regulated in the airways of atopic asthmatics after segmental allergen challenge. Eur Respir J 2004;23:876-84
  • Bochner BS, Hudson SA, Xiao HQ, Liu MC. Release of both CCR4-active and CXCR3-active chemokines during human allergic pulmonary late-phase reactions. J Allergy Clin Immunol 2003;112:930-4
  • Lloyd CM, Delaney T, Nguyen T, et al. CC chemokine receptor (CCR)3/eotaxin is followed by CCR4/monocyte- derived chemokine in mediating pulmonary T helper lymphocyte type 2 recruitment after serial antigen challenge in vivo. J Exp Med 2000;191:265-74
  • Conroy DM, Jopling LA, Lloyd CM, et al. CCR4 blockade does not inhibit allergic airways inflammation. J Leukoc Biol 2003;74:558-63
  • Chvatchko Y, Hoogewerf AJ, Meyer A, et al. A key role for CC chemokine receptor 4 in lipopolysaccharide-induced endotoxic shock. J Exp Med 2000;191:1755-64
  • Schuh JM, Power CA, Proudfoot AE, et al. Airway hyperresponsiveness, but not airway remodeling, is attenuated during chronic pulmonary allergic responses to Aspergillus in CCR4-/-mice. Faseb J 2002;16:1313-5
  • Purandare AV, Gao A, Wan H, et al. Identification of chemokine receptor CCR4 antagonist. Bioorg Med Chem Lett 2005;15:2669-72
  • Purandare AV, Wan H, Gao A, et al. Optimization of CCR4 antagonists: side-chain exploration. Bioorg Med Chem Lett 2006;16:204-7
  • Purandare AV, Wan H, Somerville JE, et al. Core exploration in optimization of chemokine receptor CCR4 antagonists. Bioorg Med Chem Lett 2007;17:679-82
  • Wang X, Xu F, Xu Q, et al. Optimization of 2-aminothiazole derivatives as CCR4 antagonists. Bioorg Med Chem Lett 2006;16:2800-3
  • Burdi DF, Chi S, Mattia K, et al. Small molecule antagonists of the CC chemokine receptor 4 (CCR4). Bioorg Med Chem Lett 2007;17:3141-5
  • Yokoyama K, Ishikawa N, Igarashi S, et al. Discovery of potent CCR4 antagonists: Synthesis and structure-activity relationship study of 2,4-diaminoquinazolines. Bioorg Med Chem 2008;16:7021-32
  • Yokoyama K, Ishikawa N, Igarashi S, et al. Potent CCR4 antagonists: Synthesis, evaluation, and docking study of 2,4-diaminoquinazolines. Bioorg Med Chem 2008;16:7968-74
  • Kuhn CF, Bazin M, Philippe L, et al. Bipiperidinyl carboxylic acid amides as potent, selective, and functionally active CCR4 antagonists. Chem Biol Drug Des 2007;70:268-72
  • Allen S, Newhouse B, Anderson AS, et al. Discovery and SAR of trisubstituted thiazolidinones as CCR4 antagonists. Bioorg Med Chem Lett 2004;14:1619-24

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.