Advanced search
Publication Cover
Expert Opinion on Therapeutic Patents Volume 19, 2009 - Issue 8
Submit an article Journal homepage
279
Views
7
CrossRef citations to date
0
Altmetric
Reviews

CCR3 antagonists: a survey of the patent literature

Leyi Gong Principal Research Scientist Department of Medicinal Chemistry, Roche Palo Alto LLC, 3431 Hillview Ave., Palo Alto, CA 94301, USA +1 650 354 7187; +1 650 855 6083; [email protected]
, PhD &
Robert S Wilhelm Senior Director of Chemistry
, PhD
Pages 1109-1132 | Published online: 28 Jul 2009

Bibliography

  • Kunkel SL, Standiford TJ, Strieter RM, Kasama T. Chemotactic cytokines: the chemokine family. Lung Biol Health Dis 1995;80:579-97
  • Lukacs NW, Hogaboam CM, Kunkel SL. Chemokines and their receptors in chronic pulmonary disease. Curr Drug Targets Inflamm Allergy 2005;4:313-7
  • Coelho AL, Hogaboam CM, Kunkel SL. Chemokines provide the sustained inflammatory bridge between innate and acquired immunity. Cytokine Growth Factor Rev 2005;16:553-60
  • Kunkel SL, Godessart N, Hogaboam CM, et al. Chemokines in animal models of inflammation. Birkhaeuser Verlag: Chemokine Biology–Basic Research and Clinical Application 2007;2:3-17
  • Hudgson S, Charlton S, Warne P. Chemokines and drug discovery. Drug News Perspect 2004;17:335-8
  • D'Elios MM, Prete GD, Amedei A. Interfering with chemolines and chemokine receptors as potential new therapeutic strategies. Expert Opin Ther Patents 2008;18:309-25
  • Murphy PM, Baggiolini M, Charo IF, et al. International union of pharmacology. XXII. Nomenclature for chemokine receptors. Pharmacol Rev 2000;52:145-76
  • Graham GJ. D6 and the atypical chemokine receptor family: Novel regulators of immune and inflammatory processes. Eur J Immunol 2009;39:342-51
  • Jose PJ, Griffiths-Johnson DA, Collin PD, et al. Eotaxin: a potent eosinophil chemoattractant cytokine detected in a guinea pig model of allergic airways inflammation. J Exp Med 1994;179:881-7
  • Daugherty BL, Siciliano SJ, DeMartino JA, et al. Cloning, expression and characterization of the human eosinophil eotaxin receptor. J Respir Med 1996;183:2349-54
  • Uguccioni M, Mackay CR, Ochensberger B, et al. High expression of the chemokine receptor CCR3 in human blood basophils. Role in activation by eotazin, MCP-4 and other chemokines. J Clin Invest 1997;100:1137-43
  • Price KS, Friend DS, Mellor EA, et al. CC chemokine receptor 3 mobilizes to the surface of human mast cells and potentiates immunoglobulin E-dependent generation of interleukin 13. Am J Respir Cell Mol Biol 2003;2:420-7
  • Sallusto F, Mackay CR, Lanzavecchia A. Selective expression of the eotaxin receptor CCR3 by human T helper 2 cells. Science 1997;277:2005-7
  • Nakamura H, Weiss ST, Israel E, et al. Eotaxin and impaired lung function in asthma. Am J Respir Crit Care Med 1999;160:1952-6
  • De Lucca GV. Recent developments in CCR3 antagonists. Curr opin Drug Discov Dev 2006;9:516-24
  • Humbles AA, Lu B, Friend DS, et al. The murine CCR3 receptor regulates both the role of eosinophils and mast cells in allergen-induced airway inflammation and hyper responsiveness. PNAS 2002;99:1479-84
  • Pope SM, Zimmermann N, Stringer KF, et al. The eotaxin chemokines and CCR3 are fundamental regulators of allergen-induced pulmonary eosinophilia. J Immunol 2005;175:5341-50
  • Ma W, Bryce PJ, Humble AA, et al. CCR3 is essential for skin eosinophilia and airway hyperresponsiveness in a murine model of allergic skin inflammation. J Clin Invest 2002;109:621-8
  • Mattes J, Yang M, Mahalingam S, et al. Intrinsic defect in T cell production of interleukin (IL-13) in the absence of both IL-5 and eotaxin prcludes the development of eosinophilia and airways hyper reactivity in experimental asthma. J Exp Med 2002;195:1433-44
  • Dent G, Hadjicharalambous C, Yoshikawa R, et al. Contribution of eotaxin-1 to eosinophil chemotactic activity of moderate and severe asthmatic sputum. Am J Respir Crit Care 2004;169:1110-7
  • Pereira S, Clark T, Darby Y, et al. Effects of anti-eotaxin monoclonal antibody CAT-213 on nasal allergen-induced rhinitis [abstract]. J Allergy Clin Immunol 2003;111:S268
  • Salib R, Salagean M, Lau L, et al. The anti-inflammatory response of anti-eotaxin monoclonal antibocy CAT-213 on nasal allergen-induced cell infiltration and activation [abstract]. J Allergy Clin Immunol 2003;111:S347
  • Nakamura H, Luster AD, Nakamura T, et al. Variant eotaxin: Its effects on the asthma phenotype. J Allergy Clin Immunol 2001;108:946-53
  • Fuentes ME, Mirzadegan T, Wilhelm RS. Chapter 4. Chemokine and cytokine modulators in Burger's Medicinal chemistry & Drug Discovery, Sixth edition. John Wiley and Sons; 2003. p. 129-202
  • Naya A, Saeki T. Chemokine CCR3 antagonists. Expert Opin Ther Patents 2004;14:7-16
  • Mori A, Ogawa K, Someya K, et al. Selective suppression of Th2-mediated airway eosinophil infiltration by low-molecular weight CCR3 antagonists. Int Immunol 2007;10:913-21
  • Schlyer S, Horuk R. I want a new drug: G-protein-coupled receptors in drug development. Drug Discov Today 2006;11:481-93
  • Kelly J, et al. US pharma: notes from the IRA conference-future drugs appearing on the horizon. Oct. 2002, Goldman Sachs
  • Das AM, Vaddi KG, Solomon KA, et al. Selective inhibition of eosinophil influx into the lung by small molecule CC chemokine receptor 3 antogonists in mouse models of allergic inflammation. J Pharm Exp Ther 2006;318:411-7
  • GlaxoSmithKline's CCR3 chemokine receptor antagonists. Expert Opin Ther Patents 2004;14:577-82
  • Mirzadegan T, Diehl F, Ebi B, et al. Identification of the binding site for a novel class of CCR2b chemokine receptor antagonists. J Biol Chem 2000;275:25562-71
  • AstraZeneca AB. Piperidine derivatives useful as modulators of chemokine receptor activity. WO2003004487; 2003
  • AstraZeneca AB. Piperidine derivatives and their use as modulators of chemokine (especially CCR3) activity. WO2003024962; 2003
  • AstraZeneca AB. Piperidine derivatives useful as modulators of chemokine receptor activity. WO2003078395; 2003
  • AstraZeneca AB. Novel piperidine derivatives for use in the treatment of chemokine mediated disease states. WO2004029041; 2004
  • AstraZeneca AB. Piperidine derivatives for the treatment of chemokine or h1 mediated disease state. WO2004085423; 2004
  • AstraZeneca AB. Chemical compounds. WO2004099144; 2004
  • AstraZeneca AB. Preparation of pharmaceutical salts of [1, 4]-bipiperidine. WO2005044268; 2005
  • AstraZeneca AB. Novel piperidines as chemokine modulators (ccr). WO2005073192; 2005
  • AstraZeneca AB. Piperidine derivates for the treatment of chemokines mediared disease. WO2005097775; 2005
  • AstraZeneca AB. Piperidines for the treatment of chemokine mediated diseases. WO2006126947; 2006
  • AstraZeneca AB. Piperidines for the treatment of chemokine mediated diseases. WO2006126948; 2006
  • AstraZeneca AB. Piperidine derivatives useful for treating osteoarthritis and osteoartrosis. WO2007114770; 2007
  • AstraZeneca AB. Novel tricyclic spiropiperidine compounds, their synthesis and their uses as modulators of chemokine receptor activity. WO2008010765; 2008
  • Bristol-Myers Squibb Co. N-Ureidoalkyl-piperidines as modulators of chemokine receptor activity. WO2004110993; 2004
  • Bristol-Myers Squibb Co. N-Ureidoalkyl-amino compounds as modulators of chemokine receptor activity WO2005048932; 2005
  • Sabroe I, Hartnell AJ, Louise A, et al. Differential regulation of eosinophil chemokine signaling via CCR3 and non-CCR3 pathways. J Immunol 1999;162:2946-55
  • Sabroe I, Peck MJ, Keulen BJV, et al. A small molecule antagonist of the chemokine receptors CCR1 and CCR3: potent inhibition of Eosinophil function and CCR3-mediated HIV-1 entry. J Biol Chem 2000;275:25985-92
  • Novartis AG. Azetidine derivatives as CCR-3 receptor antagonists. WO2003077907; 2003
  • Novartis AG. Piperidin-acetamide derivatives for the treatment of inflammatory or allergic diseases. WO2008092844; 2008
  • Bristol-Myers Squibb Co. Substituted piperidines as modulators of chemokine receptor activity. US2008081824; 2008
  • Bristol-Myers Squibb Co. Substituted spiro azabicyclics as modulators of chemokine receptor activity. WO2005080376; 2005
  • Wacker DA, Varnes JG, Gardner DS, 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
  • Batt DG, Houghton GC, Roderick J, et al. N-Arylalkylpiperidine urea derivatives as CC chemokine receptor-3 (CCR3) antagonists. Bioorg Med Chem Lett 2005;15:787-91
  • Watson PS, Jiang B, Harrison K, et al. 2,4-Disubstituted piperidines as selective CC chemokine receptor 3 (CCR3) antagonists: synthesis and selectivity. Bioorg Med Chem Lett 2006;16:5695-9
  • 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
  • Duncia JV, Santella JB, Gardner DS, et al. From rigid cyclic templates to conformationally stabilized acyclic scaffolds. Part I: the discovery of CCR3 antagonist development candidate BMS-639623 with picomolar inhibition potency against eosinophil chemotaxis. Bioorg Med Chem Lett 2008;18:576-85
  • Duncia JV, Gardner DS, Santella JB III, et al. From rigid cyclic templates to conformationally stabilized acyclic scaffolds. Part II: acyclic replacements for the (3S)-3-benzylpiperidine in a series of potent CCR3 antagonists. Bioorg Med Chem Lett 2008;18:586-95
  • Dhar TG, Yang G, Davis P, et al. Urea based CCR3 antagonists employing a tetrhydro-1,3-oxazin-2-one spacer. Bioorg Med Chem Lett 2009;19:96-9
  • Bristol-Myers Squibb Co. N-Ureidoalkyl-piperidines as modulators of chemokine receptor activity. WO2004024682; 2004
  • Boehringer Ingelheim Pharma GmbH & Co. Novel substituted piperidyl-propane-thiols. WO2008049875; 2008
  • Boehringer Ingelheim Pharma GmbH & Co. Piperidyl-propane-thiol CCR3 modulators. WO2008049874; 2008
  • Boehringer Ingelheim Pharma GmbH & Co. Novel Piperidine-substituted indoles. US2006247230; 2006
  • Boehringer Ingelheim Pharma GmbH & Co. Novel piperidine substituted indoles or heteroderivatives thereof. WO2005049559; 2005
  • Boehringer Ingelheim Pharma GmbH & Co. Alkyl- and piperidine-substituted benzimidazole-derivates. WO2006013073; 2006
  • Boehringer Ingelheim Pharma GmbH & Co. Haloalkyl- and piperidine-substituted benzimidazole-derivatives. WO2005019203; 2005
  • Boehringer Ingelheim Pharma GmbH & Co. N-(Heterobicycloalkanes)-substituted indoles or heteroderivatives thereof. WO2005005425; 2005
  • AstraZeneca AB. Piperidine derivatives, their process for preparation, their use as therapeutic agents and pharmaceutical compositions containing them. WO2007102767; 2007
  • AstraZeneca AB. Piperidine derivatives, their process for preparation, their use as therapeutic agents and pharmaceutical compositions containing them. WO2007102768; 2007
  • AstraZeneca AB. Chemical compounds III. WO2007102769; 2007
  • AstraZeneca AB. Novel piperidine derivatives. WO2007011293; 2007
  • Bryan SA, Jose PJ, Topping JR, et al. Responses of leukocytes to chemokines in whole blood and their antagonism by novel CC-chemokine receptor 3 antagonists. Am J Respir Crit Care Med 2002;165:1602-9
  • Hoffmann-La Roche AG. Piperidinyl and piperazinyl compounds substituted with bicyclo-heterocyclylalkyl groups useful as CCR3 receptor antagonists. US2005090504; 2005
  • Hoffmann-La Roche AG. Cyclic amine derivatives-CCR-3 receptor antagonists. US6339087; 2002
  • Hoffmann-La Roche AG. CCR-3 receptor antagonists. WO2004076448; 2004
  • Gong L, Hogg JH, Collier J, et al. Design and synthesis of novel CCR3 antagonists. Bioorg Med Chem Lett 2003;13:3597-600
  • Schering-Plough Corp. Piperidine derivatives useful as CCR3 antagonists. US20050182095; 2005
  • 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
  • Teijin Limited. Piperidine derivatives having CCR3 antagonism. WO2003087089; 2003
  • Teijin Limited. 4,4-Disubstituted piperidine derivatives having CCR3 antagonism. WO2003091245; 2003
  • Mitsubishi Pharma Corp. N-oxide compounds. WO2004037817; 2004
  • Mitsubishi Pharma Corp. Morpholine compound. WO2006028284; 2006
  • Mitsubishi Pharma Corp. Salt of morpholine compound. WO2008007691; 2008
  • AstraZeneca AB. N-Benzyl-morpholine derivatives as modulators of the chemokine receptor. WO2007011292; 2007
  • Novartis AG. Piperazine derivatives with CCR3 inhibiting activity. WO2006015851; 2006
  • Boehringer Ingelheim Pharma GmbH & Co. 1-Phenyl-1,2-diaminoethane derivatives as modulators of the chemokine receptor activity. US2004063779; 2004
  • Novartis AG. Organic compounds. WO2005075420; 2005
  • Bristol-Myers Squibb Co. Substituted fused bicyclic amines as modulators of chemokine receptor activity. WO2005079497; 2005
  • Novartis AG. 1, 3-Disubstituted azetidine derivatives for use as CCR-3 receptor antagonists in the treatment of inflammatory and allergic diseases. WO2005026113; 2005
  • Novartis AG. Organic compounds. WO2006015854; 2006
  • Novartis AG. Organic compounds. WO2006015852; 2006
  • Novartis AG. Arylurea derivatives as modulators of chemokine receptor activity WO2007048771; 2007
  • Sanofi-Aventis. Amino-alkyl-amide derivatives as CCR3 receptor ligands. WO2007034251; 2007
  • Sanofi-Aventis. Amino-alkyl-amide derivatives as CCR3 receptor liquids. WO2007034252; 2007
  • Sanofi-Aventis. Amino-alkyl-amide derivatives as CCR3 receptor ligands. WO2007034253; 2007
  • Sanofi-Aventis. Amino-alkyl-amide derivatives as CCR3 receptor ligands. WO2007034254; 2007
  • Pegurier C, Collart P, Danhaive P, et al. Pyrrozolone methylamino piperidine derivatives as novel CCR3 antagonists. Bioorg Med Chem Lett 2007;17:4228-31
  • Kowa Company, Ltd. Tetrahydroisoquinoline compound. WO2008123582; 2008
  • Novartis AG. Use of fused imidazole derivatives to mediate CCR3 related conditions. WO2007025751; 2007
  • Bayer Healthcare AG. 2-Phenoxy-and 2-phenylsulfomamide derivatives with CCR3 antagonistic activity for the treatment of asthma and other inflammatory or immunological disorders. WO2004084898; 2004
  • Boehringer Ingelheim Pharma Gmbh & Co. Pyrrolidinohydrochinazolines. WO2004072074; 2004
  • Anderskewitz R, Bauer R, Bodenback G, et al. Pyrrolidinohydroquinazolines-a novel class of CCR3 modulators. Bioorg Med Chem Lett 2005;15:669-73
  • Gauvreau GM, Boulet LP, Cockroft DW, et al. Antisense therapy against CCR3 and the common beta chain attenuates allergen-induced eosinophilic responses. Am Respir Crit Care Med 2008;177:952-8
  • Hodgson S, Charlton S, Warne P. Chemokines and drug discovery. Drug New Perspect 2004;15:335-8
  • Peterson D, Ognjenovic M. American chemistry society-228th National meeting: inflammation. IDrugs 2004;7:904-6
  • Hansel T. Study protocol for GW766994: a double blind randomized two way crossover placebo-controlled study in 12 subjects with seasonal allergic rhinitis to investigate the degree of inhibition afforded by GW766994 against eotazin-induced eosinophilia in nasal and skin tissues. Available from: http://www.rbht.nhs.uk/research/projects/?entryid31 = 46250& q = 0%c2%acGW766994%c2%ac [last accessed 23 February 2009]
  • Perks B. Synthetic chemists catch their breath. Chem World 2004;1(8)
  • Gleich GJ. Mechanisms of eosinophil-associated inflammation. J Allergy Clin Immunol 2000;105:651-65
  • Humbles AA, Lloyd CM, McMillan SJ, et al. A critical role for eosinophils in allergic airways remodeling. Science 2004;305:1776-9
  • Blyth DI, Wharton TF, Pedrick MS, et al. Airway subepithelial fibrosis in a murine model of atopic asthma. Am J Respir Cell Mol Biol 2000;23:241-6
  • Flood-Page P, Menzies-Gow AN, Phipps S, et al. Anti-IL-5 treatment reduces deposition of ECM proteins in the bronchial subepithelial basement membrane of mild atopic asthmatics. J Clin Invest 2003;112:1029-36
  • Sanderson CJ. Interleukin-5, eosinophils and disease. Blood 1992;79:3101-9
  • Flood-Page P, Swenson C, Faiferman I, et al. A study to evaluate safety and efficacy of mepolizumab in patients with moderate persistent asthma. Am J Respir Crit Care Med 2007;176:1062-71
  • Flood-Page PT, Menzies-Gow AN, Kay AB, Robinson DS. Eosinophil's role remains uncertain as anti-interleukin-5 only partially depletes numbers in asthmatic airway. Am J Respir Crit Care Med 2003;167:199-204
  • O'Byrne PM. The demise of anti-IL-5 for asthma, or not. Am J Respir Crit Care Med 2007;176:1059-61
  • Bochner B. Verdict in the case of therapies versus eosinophils: the jury is still out. J Allergy Clin Immunol 2004;113:3-9
  • O'Byrbe OM, Inman MD, Parameswaran K. The trials and tribulations of IL-5, eosinophils, and allergic asthma. J Allergy Clin Immunol 2001;108:503-8
  • Kips JC, O'Connor BJ, Langley SJ, et al. Effect of SCH55700, a humanized anti-human interleukin-5 antibody, in severe persistent asthma: a pilot study. Am J Respir Crit Care Med 2003;167:1655-9
  • Liu LY, Sedgwick JB, Bates ME, et al. Decreased expression of membrane IL-5 receptor alpha on human eosinophils: I. Loss of membrane IL-5 receptor alpha on airway eosinophils and increase soluble IL-5 receptor alpha in the airway after allergen challenge. J Immunol 2002;169:6452-8
  • Liu LY, Sedgwick JB, Bates ME, et al. Decreased expression of membrane IL-5 receptor alpha on human eosinophils: II. IL-5 down-modulates its receptor via a proteinase-mediated process. J Immunol 2002;169:6459-66
  • Gregory B, Kirchem A, Phipps S, et al. Differential regulation of human eosinophil IL-3, IL-5 and GS-CSF receptor alpha-chain expression by cytokines: IL-3, IL-5, GM-CSF down-regulate IL-5 receptor alpha expression with loss of IL-5 responsiveness, but up-regulate IL-3 receptor alpha expression. J Immunol 2003;170:5359-66
  • IL-5R Ph II trial announced by MedImmune on news-medical.net. Available from: http://www.news-medical.net/?id = 43864 [Last accessed 19 February 2009]
  • Haldar P, Brightling CE, Hargadon B, et al. Mepolizumab and exacerbations of refractory eosinophilic asthma. N Engl J Med 2009;360:973-84
  • Nair P, Pizzichini MMM, Kjarsgaard M, et al. Mepolizumab for predisone-dependent asthma with sputum eosinophilia. N Engl J Med 2009;360:985-93
  • Pease JE, Horuk R. Chemokine receptor antagonists: Part 1. Expert Opin Ther Patents 2009;19:39-58
  • Murdoch RD. The Challenges of drug discovery & development, an oral presentation, 4th James Black Conference. University of Hertfordshire, 2006

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:

Order Reprints Request Corporate Permissions

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:

Request Academic Permissions

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.

Related research

People also read lists articles that other readers of this article have read.

Recommended articles lists articles that we recommend and is powered by our AI driven recommendation engine.

Cited by lists all citing articles based on Crossref citations.
Articles with the Crossref icon will open in a new tab.