Progress in the discovery of CC chemokine receptor 2 antagonists, 2009 – 2012

Bibliography

• Allen SJ, Crown SE, Handel TM. Chemokine: receptor structure, interactions, and antagonism. Annu Rev Immunol 2007;25:787-820
   PubMed Web of Science ®Google Scholar
• Sallusto F, Baggiolini M. Chemokines and leukocyte traffic. Nat Immunol 2008;9:949-52
   PubMed Web of Science ®Google Scholar
• Koelink PJ, Overbeek SA, Braber S, Targeting chemokine receptors in chronic inflammatory diseases: an extensive review. Pharmacol Ther 2012;133:1-18
   PubMed Web of Science ®Google Scholar
• Proudfoot AEI, Power CA, Schwarz MK. Anti-chemokine small molecule drugs: a promising future? Expert Opin Investig Drugs 2010;19:345-55
   PubMed Web of Science ®Google Scholar
• Horuk R. Chemokine receptor antagonists: overcoming developmental hurdles. Nat Rev Drug Disc 2009;8:23-33
   PubMed Web of Science ®Google Scholar
• Viola A, Luster AD. Chemokines and their receptors: drug targets in immunity and inflammation. Annu Rev Pharmacol Toxicol 2008;48:171-97
   PubMed Web of Science ®Google Scholar
• Gulick RM, Lalezari J, Goodrich J, Maraviroc for previously treated patients with R5 HIV-1 infection. N Engl J Med 2008;359:1429-41
   PubMed Web of Science ®Google Scholar
• DiPersio JF, Stadtmauer EA, Nademanee A, Plerixafor and G-CSF versus placebo and G-CSF to mobilize hematopoietic stem cells for autologous stem cell transplantation in patients with multiple myeloma. Blood 2009;113:5720-6
   PubMed Web of Science ®Google Scholar
• Eksteen B, Adams DH. GSK-1605786, a selective small-molecule antagonist of the CCR9 chemokine receptor for the treatment of Crohn's disease. IDrugs 2010;13:472-81
   PubMed Web of Science ®Google Scholar
• GSK1605786A in the Maintenance of Remission in Subjects With Crohn's Disease (SHIELD-2). NCT01316939. 2013 www.clinicaltrials.gov [accessed 9/8/2012]
   Google Scholar
• Gordon S, Taylor PR. Monocyte and macrophage heterogeneity. Nat Rev Immunol 2005;5:953-64
   PubMed Web of Science ®Google Scholar
• Serbina NV, Pamer EG. Monocyte emigration from bone marrow during bacterial infection requires signals mediated by chemokine receptor CCR2. Nat Immunol 2006;7:311-17
   PubMed Web of Science ®Google Scholar
• Tsou CL, Peters W, Si Y, Critical roles for CCR2 and MCP-3 in monocyte mobilization from bone marrow and recruitment to inflammatory sites. J Clin Invest 2007;117:902-9
   PubMed Web of Science ®Google Scholar
• Wisniewski T, Bayne E, Flanagan J, Assessment of chemokine receptor function on monocytes in whole blood: in vitro and ex vivo evaluations of a CCR2 antagonist. J Immunol Methods 2010;352:101-10
   PubMed Web of Science ®Google Scholar
• Zlotnik A, Yoshie O. The chemokine superfamily revisited. Immunity 2012;36:705-16
   PubMed Web of Science ®Google Scholar
• Leuschner F, Dutta P, Gorbatov R, Therapeutic siRNA silencing in inflammatory monocytes in mice. Nat Biotech 2011;29:1005-10
   PubMed Web of Science ®Google Scholar
• Charo IF, Ransohoff RM. The many roles of chemokines and chemokine receptors in inflammation. N Engl J Med 2006;354:610-21
   PubMed Web of Science ®Google Scholar
• Feria M, Diaz-Gonzalez F. The CCR2 receptor as a therapeutic target. Expert Opin Ther Pat 2006;16:49-57
   Web of Science ®Google Scholar
• Kang YS, Cha JJ, Hyun YY, Cha DR. Novel C-C chemokine receptor 2 antagonists in metabolic disease: a review of recent developments. Expert Opin Investig Drugs 2011;20:745-56
   PubMed Web of Science ®Google Scholar
• Kalinowska A, Losy J. Investigational CC chemokine receptor 2 antagonists for the treatment of autoimmune disease. Expert Opin Investig Drugs 2008;17:1267-79
   PubMed Web of Science ®Google Scholar
• Vergunst CE, Gerlag DM, Lopatinskaya L, Modulation of CCR2 in rheumatoid arthritis: a double-blind, randomized, placebo-controlled clinical trial. Arthritis Rheum 2008;58:1931-9
   PubMed Web of Science ®Google Scholar
• Gilbert J, Lekstrom-Himes J, Donaldson D, Effect of CC chemokine receptor 2 CCR2 blockade on serum C-reactive protein in individuals at atherosclerotic risk and with a single nucleotide polymorphism of the Monocyte Chemoattractant Protein-1 promoter region. Am J Cardiol 2011;107:906-11
   PubMed Web of Science ®Google Scholar
• Jones KL, Maguire JJ, Davenport AP. Chemokine receptor CCR5: from AIDS to atherosclerosis. Br J Pharmacol 2011;162:1453-69
   PubMed Web of Science ®Google Scholar
• Ness TL, Kunkel SL, Hogaboam CM. CCR5 antagonists: the answer to inflammatory disease? Expert Opin Ther Pat 2006;16:1051-65
   PubMed Web of Science ®Google Scholar
• Zhao Q. Dual targeting of CCR2 and CCR5: therapeutic potential for immunologic and cardiovascular diseases. J Leukoc Biol 2010;88:41-55
   PubMed Web of Science ®Google Scholar
• Pease JE, Horuk R. Small molecule antagonists of chemokine receptors – is promiscuity a virtue? Curr Top Med Chem 2010;10:1351-8
   PubMed Web of Science ®Google Scholar
• Carter PH. Chemokine receptor antagonism as an approach to anti-inflammatory therapy: 'just right' or plain wrong? Curr Opin Chem Biol 2002;6:510-25
   PubMed Web of Science ®Google Scholar
• Singh IP, Chauthe SK. Small molecule HIV entry inhibitors: part I. Chemokine receptor antagonists: 2004 – 2010. Expert Opin Ther Pat 2011;21:227-69
   PubMed Web of Science ®Google Scholar
• Cumming JG, Tucker H, Oldfield J, 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 2012;22:1655-9
   PubMed Web of Science ®Google Scholar
• Kothandan G, Gadhe CG, Cho SJ. Structural insights from binding poses of CCR2 and CCR5 with clinically important antagonists: a combined in silico study. PLoS One 2012;7(3):e32864
   Web of Science ®Google Scholar
• Carter PH, Tebben AJ. Chapter 12. The use of receptor homology modeling to facilitate the design of selective chemokine receptor antagonists. Methods Enzymol 2009;461:249-79
   PubMed Web of Science ®Google Scholar
• Hall SE, Mao A, Nicolaidou V, Elucidation of binding sites of dual antagonists in the human chemokine receptors CCR2 and CCR5. Mol Pharmacol 2009;75:1325-36
   PubMed Web of Science ®Google Scholar
• Pease JE, Horuk R. Chemokine receptor antagonists: part 1. Expert Opin Ther Pat 2009;19:39-58
   PubMed Web of Science ®Google Scholar
• Pease JE, Horuk R. Chemokine receptor antagonists: part 2. Expert Opin Ther Pat 2009;19:199-221
   PubMed Web of Science ®Google Scholar
• Pease JE, Horuk R. Chemokine receptor antagonists. J Med Chem 2012;55:9363-92
   PubMed Web of Science ®Google Scholar
• Wijtmans M, Scholten DJ, de Esch IJP, Therapeutic targeting of chemokine receptors by small molecules. Drug Discov Today 2012;9:e229-36
   Google Scholar
• Struthers M, Pasternak A. CCR2 Antagonists. Curr Top Med Chem 2010;10:1278-98
   PubMed Web of Science ®Google Scholar
• Carter PH, Cherney RJ, Mangion IK. Advances in the discovery of CC chemokine receptor-2 antagonists. Ann Rep Med Chem 2007;42:211-27
   Web of Science ®Google Scholar
• Xia M, Sui Z. Recent developments in CCR2 antagonists. Expert Opin Ther Pat 2009;19:295-303
   PubMed Web of Science ®Google Scholar
• Laborde E, Macsata RW, Meng F, Discovery, optimization, and pharmacological characterization of novel heteroaroylphenylureas antagonists of C-C chemokine ligand 2 function. J Med Chem 2011;54:1667-81
   PubMed Web of Science ®Google Scholar
• Severin IC, Souza AL, Davis JH, Properties of 7ND-CCL2 are modulated upon fusion to Fc. Protein Eng Des Sel 2012;25:213-22
   PubMed Web of Science ®Google Scholar
• Baeck C, Wehr A, Karlmark KR, Pharmacological inhibition of the chemokine CCL2 (MCP-1) diminishes liver macrophage infiltration and steatohepatitis in chronic hepatic injury. Gut 2012;61:416-26
   PubMed Web of Science ®Google Scholar
• Izhak L, Wildbaum G, Zohar Y, A novel recombinant fusion protein encoding a 20-amino acid residue of the third extracellular (E3) domain of CCR2 neutralizes the biological activity of CCL2. J Immunol 2009;183:732-9
   PubMed Web of Science ®Google Scholar
• Obmolova G, Teplyakov A, Malia TJ, Structural basis for high selectivity of anti-CCL2 neutralizing antibody CNTO888. Mol Immunol 2012;51:227-33
   PubMed Web of Science ®Google Scholar
• Merck & Co., Inc. Preparation of [(1R,3S)-3-isopropyl-3-[[3-(trifluoromethyl)-7,8-dihydro-1,6-naphthyridin-6(5H)-yl]carbonyl]cyclopentyl][(3S,4S)-3-methoxytetrahydro-2H-pyran-4-yl]amine salt as chemokine receptor CCR-2 antagonist. WO2005044795; 2005
   Google Scholar
• Yang L, Jiao RX, Moyes C, The discovery of MK-0812, a potent and selective CCR2 antagonist. 233rd ACS National Meeting; Chicago; 2007
   Google Scholar
• Moree WJ, Kataoka K, Ramirez-Weinhouse MM, Small molecule antagonists of the CCR2b receptor. Part 2: discovery process and initial structure-activity relationships of diamine derivatives. Bioorg Med Chem Lett 2004;14:5413-16
   PubMed Web of Science ®Google Scholar
• Moree WJ, Kataoka K, Ramirez-Weinhouse MM, Potent antagonists of the CCR2b receptor. Part 3: SAR of the (R)-3-aminopyrrolidine series. Bioorg Med Chem Lett 2008;18:1869-73
   PubMed Web of Science ®Google Scholar
• Xia M, Hou C, DeMong DE, Synthesis, structure-activity relationship and in vivo antiinflammatory efficacy of substituted dipiperidines as CCR2 antagonists. J Med Chem 2007;50:5561-3
   PubMed Web of Science ®Google Scholar
• Carter PH. Spiroindenes and spiroindanes as antagonists of CC chemokine receptor 2: WO 2009023754. Expert Opin Ther Pat 2010;20:283-9
   PubMed Web of Science ®Google Scholar
• Kettle JG, Faull AW, Barker AJ, N-Benzylindole-2-carboxylic acids: potent functional antagonists of the CCR2b chemokine receptor. Bioorg Med Chem Lett 2004;14:405-8
   PubMed Web of Science ®Google Scholar
• Baba M, Nishimura O, Kanzaki N, A small-molecule, nonpeptide CCR5 antagonist with highly potent and selective anti-HIV-1 activity. Proc Natl Acad Sci USA 1999;96:5698-703
   PubMed Web of Science ®Google Scholar
• Kothandaraman S, Donnely KL, Butora G, Design, synthesis and structure-activity relationship of novel CCR2 antagonists. Bioorg Med Chem Lett 2009;19:1830-4
   PubMed Web of Science ®Google Scholar
• Merck Sharp & Dohme Corp. Cyclohexane substituted amino cyclopentane derivatives as useful CCR2 antagonists. WO 2012/125663; 2012
   Google Scholar
• Olzinksi AR, Turner GH, Bernard RE, Pharmacological inhibition of C-C chemokine receptor 2 decreases macrophage infiltration in the aortic root of the human C-C chemokine receptor 2/apolipoprotein E-/- mouse: magnetic resonance imaging assessment. Arterioscler Thromb Vasc Biol 2010;30:253-9
   PubMed Web of Science ®Google Scholar
• Pasternak A, Goble SD, Struthers M, Discovery of a potent and orally bioavailable CCR2 and CCR5 Dual antagonist. ACS Med Chem Lett 2010;1:14-18
   Web of Science ®Google Scholar
• Zheng C, Cao G, Xia M, Discovery of INCB10820/PF-4178903, a potent, selective, and orally bioavailable dual CCR2 and CCR5 antagonist. Bioorg Med Chem Lett 2011;21:1442-6
   PubMed Web of Science ®Google Scholar
• Hughes RO, Rogier DJ, Devraj R, Discovery of ((1S,3R)-1-isopropyl-3-((3S,4S)-3-methoxy-tetrahydro-2H-pyran-4-ylamino)cyclopent yl)(4-(5-(trifluoromethyl)pyridazin-3-yl)piperazin-1-yl)methanone, PF-4254196, a CCR2 antagonist with an improved cardiovascular profile. Bioorg Med Chem Lett 2011;21:2626-30
   PubMed Web of Science ®Google Scholar
• Pfizer, Inc. 3-Aminocyclopentanecarboxamides as chemokine receptor modulators. WO2010061329; 2010
   Google Scholar
• Hughes RO, Rogier DJ, Rajesh D, Discovery of a dual CCR2/CCR5 antagonist with a superior cardiovascular profile for the treatment of autoimmune diseases. 242nd ACS National Meeting; Denver; 2011
   Google Scholar
• Trujilo JI, Huang W, Hughes RO, Design and synthesis of novel CCR2 antagonists: Investigation of non-aryl/heteroaryl binding motifs. Bioorg Med Chem Lett 2011;21:1827-31
   PubMed Web of Science ®Google Scholar
• Bristol-Myers Squibb Co. Benzylpyrrolidinone derivatives as modulators of chemokine receptor activity. WO 2011/100227; 2011
   Google Scholar
• Abbott Laboratories. Octahydropentalene compounds as chemokine receptor antagonists. WO 2009/042193; 2009
   Google Scholar
• Winters MP, O'Neill J, Hou C, Discovery and profile of cyclopentylamines as inhibitors of chemokine receptor CCR2. 244th ACS National Meeting; Philadelphia; 2012
   Google Scholar
• Epix Delaware, Inc. Carboxamide compounds and their use as antagonists of the chemokine CCR2 receptor. WO 2009/076404; 2009
   Google Scholar
• Epix Delaware, Inc. Carboxamide compounds and their use as chemokine receptor antagonists. WO 2009/076512; 2009
   Google Scholar
• Yang Ji Chemical Co., Ltd. 3-Aminopyrrolidine derivatives as CCR2 antagonists. WO 2010/074409; 2010
   Google Scholar
• Yang Ji Chemical Co., Ltd. Piperazinyl 3-aminopyrrolidine derivatives as a CCR2 antagonist. WO 2011/004972; 2011
   Google Scholar
• Lim JW, Oh Y, Kim J-H, Synthesis and biological evaluation of 3-aminopyrrolidine derivatives as CC chemokine receptor 2 antagonists. Bioorg Med Chem Lett 2010;20:2099-102
   PubMed Web of Science ®Google Scholar
• Xue C-B, Wang A, Meloni D, Discovery of INCB3344, a potent, selective, and orally bioavailable antagonist of human and murine. CCR2. Bioorg Med Chem Lett 2010;20:7473-8
   PubMed Web of Science ®Google Scholar
• Shin N, Baribaud F, Wang K, Pharmacological characterization of INCB3344, a small molecule antagonist of human CCR2. Biochem Biophys Res Commun 2009;387:251-5
   PubMed Web of Science ®Google Scholar
• Xue C-B, Feng H, Cao G, Discovery of INCB3284, a potent, selective, and orally bioavailable hCCR2 antagonist. ACS Med Chem Lett 2011;2:450-4
   PubMed Web of Science ®Google Scholar
• Xue C-B, Wang A, Han Q, Discovery of INCB8761/PF-4136309, a potent, selective, and orally bioavailable CCR2 antagonist. ACS Med Chem Lett 2011;2:913-18
   PubMed Web of Science ®Google Scholar
• Janssen Pharmaceutica NV. 4-Azetidinyl-1-phenyl-cyclohexane antagonists of CCR2. WO 2010/121046; 2010
   Google Scholar
• Janssen Pharmaceutica NV. 4-Azetidinyl-1-heteroaryl-cyclohexane antagonists of CCR2. WO 2010/121011; 2010
   Google Scholar
• Janssen Pharmaceutica NV. 4-Azetidinyl-1-heteroatom linked-cyclohexane antagonists of CCR2. WO 2010/121036; 2010
   Google Scholar
• Zhang X, Hufnagel H, Markotan T, Overcoming hERG activity in the discovery of a series of 4-azetidinyl-1-aryl-cyclohexanes as CCR2 antagonists. Bioorg Med Chem Lett 2011;21:5577-82
   PubMed Web of Science ®Google Scholar
• Johnson & Johnson. 4-Azetidinyl-1-heteroaryl-cyclohexanol antagonists of CCR2. US2010/0144695; 2010
   Google Scholar
• Zhang X, Hou C, Hufnagel H, Discovery of a novel CCR2 antagonist as development candidate via divergent SARs of CCR2 and hERG. 244th ACS National Meeting; Philadelphia; 2012
   Google Scholar
• Zhang X, Hou C, Hufnagel H, Discovery of a 4-azetidinyl-1-thiazoyl-cyclohexane CCR2 antagonist as a development candidate. ACS Med Chem Lett 2012;3:1039-44
   PubMed Web of Science ®Google Scholar
• Zhang X, Hufnagel H, Hou C, Design, synthesis and SAR of indazole and benzoisoxazole containing 4-azetidinyl-1-aryl-cyclohexanes as CCR2 antagonists. Bioorg Med Chem Lett 2011;21:6042-8
   PubMed Web of Science ®Google Scholar
• Janssen Pharmaceutica NV. Cyclohexyl-azetidinyl antagonists of CCR2. WO 2011/156554; 2011
   Google Scholar
• Janssen Pharmaceutica NV. Cyclohexyl-azetidinyl antagonists of CCR2. WO 2011/159854; 2011
   Google Scholar
• Subasinghe NL, Lanter J, Markotan T, A novel series of N-(azetidin-3-yl)-2-(heteroarylamino)acetamide CCR2 antagonists. Bioorg Med Chem Lett. 2013.http://dx.doi.org/10.1016/j.bmcl.2012.12.017
   Google Scholar
• Merck Sharp & Dohme Corp. Substituted 3-azabicyclo[3.1.0]hexane derivatives useful as CCR2 antagonists. WO 2012/125661; 2012
   Google Scholar
• Carter PH, Brown GD, King SR, Discovery of an orally-bioavailable CC Chemokine Receptor 2 antagonist derived from an acyclic diaminoalcohol backbone. Bioorg Med Chem Lett 2012;22:3311-16
   PubMed Web of Science ®Google Scholar
• Cherney RJ, Brogan JB, Mo R, Discovery of trisubstituted cyclohexanes as potent CC chemokine receptor 2 (CCR2) antagonists. Bioorg Med Chem Lett 2009;19:597-601
   PubMed Web of Science ®Google Scholar
• Cherney RJ, Mo R, Meyer DT, Novel sulfone-containing di- and trisubstituted cyclohexanes as potent CC chemokine receptor 2 (CCR2) antagonists. Bioorg Med Chem Lett 2009;19:3418-22
   PubMed Web of Science ®Google Scholar
• Yang MG, Xiao Z, Shi Q, Synthesis of 3-phenylsulfonylmethyl cyclohexylaminobenzamide-derived antagonists of CC chemokine receptor 2 (CCR2). Bioorg Med Chem Lett 2012;22:1384-7
   PubMed Web of Science ®Google Scholar
• Cherney RJ, Mo R, Meyer DT, gamma-Lactams as glycinamide replacements in cyclohexane-based CC chemokine receptor 2 (CCR2) antagonists. Bioorg Med Chem Lett 2010;20:2425-30
   PubMed Web of Science ®Google Scholar
• Cherney RJ, Mo R, Meyer DT, Benzimidazoles as benzamide replacements within cyclohexane-based CC chemokine receptor 2 (CCR2) antagonists. Bioorg Med Chem Lett 2012;22:6181-4
   PubMed Web of Science ®Google Scholar
• Bristol-Myers Squibb Co. N-((1R,2S,5R)-5-(tert-butylamino)-2-((S)-3-(7-tert-butylpyrazolo[1,5-A][1,3,5]triazin-4-ylamino)-2-oxopyrrolidin-1-yl)cyclohexyl)acetamide, a dual modulator of chemokine receptor activity, crystalline forms and processes. US 2011/0086857; 2011
   Google Scholar
• Norman P. A dual CCR2/CCR5 chemokine antagonist, BMS-813160? Evaluation of WO2011046916. Expert Opin Ther Pat 2011;21:1919-24
   PubMed Web of Science ®Google Scholar
• Lanter JC, Markotan TP, Zhang X, The discovery of novel cyclohexylamide CCR2 antagonists. Bioorg Med Chem Lett 2011;21:7496-501
   PubMedGoogle Scholar
• Janssen Pharmaceutica NA. 4-Substituted-cyclohexylamino-4-piperidinyl-acetamide antagonists of CCR2. WO 2012/075115; 2012
   Google Scholar
• Johnson & Johnson. Piperidyl acrylamide antagonists of CCR2. US 2009/0318498; 2009
   Google Scholar
• Johnson & Johnson. Substituted dipiperidine CCR2 antagonists. US 2007/0197590; 2007
   Google Scholar
• Glaxo Group Ltd. Preparation of piperidinylhydroxyethylpiperidines as modulators of chemokine receptors. WO2009/049113; 2009
   Google Scholar
• Glaxo Group Ltd. Spirodihydrobenzofuran derivatives as chemokine receptors modulators and their preparation, pharmaceutical compositions and use in the treatment of diseases. WO2009/061881; 2009
   Google Scholar
• Glaxo Group Ltd. Spiroindenes and spiroindanes as modulators of chemokine receptors. WO2009/023754; 2009
   Google Scholar
• Glaxo Group Ltd. Preparation of spiro-indoline derivatives as chemokine receptor modulators. WO2008/157741; 2008
   Google Scholar
• Glaxo Group Ltd. Stereoselective hydrogenation of a ketone. WO 2010/099098; 2010
   Google Scholar
• Glaxo Group Ltd. Oxazoles as modulators of chemokine receptors. WO 2010/080873; 2010
   Google Scholar
• Glaxo Group Ltd. Indolinyl-, benzofuranyl-, and benzothienyl-amides as modulators of chemokine receptors. WO 2010/093578; 2010
   Google Scholar
• Sehon CA, Wang G, Viet A, Reviving the dead: Re-evaluation and optimization of a former terminated lead series allows for the identification of a candidate CCR2 antagonist. 242nd ACS National Meeting, Denver; 2011
   Google Scholar
• Hoffman-La Roche, Inc. Novel diazepan derivatives. US 2007/0249589; 2007
   Google Scholar
• F. Hoffman-La Roche AG. Novel heterocycl compounds. WO 2009/010429; 2009
   Google Scholar
• Sayyed SG, Ryu M, Kulkarni OP, An orally active chemokine receptor CCR2 antagonist prevents glomerulosclerosis and renal failure in type 2 diabetes. Kidney Int 2011;80:68-78
   PubMed Web of Science ®Google Scholar
• Xia M, Hou C, Demong D, Substituted dipiperidine alcohols as potent CCR2 antagonists. Bioorg Med Chem Lett 2008;18:3562-4
   PubMed Web of Science ®Google Scholar
• Xia M, Hou C, DeMong D, Synthesis and structure-activity relationship of 7-azaindole piperidine derivatives as CCR2 antagonists. Bioorg Med Chem Lett 2008;18:6468-70
   PubMed Web of Science ®Google Scholar
• F. Hoffman-La Roche AG. Novel heterocycl compounds for treatment of cardiovascular disease. WO 2010/006938; 2010
   Google Scholar
• Adam J-M, Aebi J, Binggeli A, Novel heterocycl compounds. US 2010/0022518; 2010
   Google Scholar
• Aebi J, Binggeli A, Green L, Novel heterocycl compounds. US 2011/0092698; 2011
   Google Scholar
• Aebi J, Binggeli A, Green L, Novel bicyclic compounds. US 2011/0082294; 2011
   Google Scholar
• Cumming JG, Bower JF, Waterson D, The design and synthesis of novel, potent and orally bioavailable N-aryl piperazine-1-carboxamide CCR2 antagonists with very high hERG selectivity. Bioorg Med Chem Lett 2012;22:3895-9
   PubMed Web of Science ®Google Scholar
• Astra-Zeneca Pharmaceuticals LP. (4-tert-butylpiperazin-2-yl)(piperazin-1-yl)methanone-N-carboxamide derivatives. US2010/0152197; 2010
   Google Scholar
• Boehringer Ingelheim International GMBH. CCR2 receptor antagonists and uses thereof. WO 2008/145681; 2008
   Google Scholar
• Peace S, Philp J, Brooks C, Identification of a sulfonamide series of CCR2 antagonists. Bioorg Med Chem Lett 2012;20:3961-4
   Web of Science ®Google Scholar
• Wang GZ, Haile PA, Daniel T, CCR2 receptor antagonists: optimization of biaryl sulfonamides to increase activity in whole blood. Bioorg Med Chem Lett 2011;21:7291-4
   PubMedGoogle Scholar
• Smethurst CA, Bevan N, Brooks C, In vivo activity of an azole series of CCR2 antagonists. Bioorg Med Chem Lett 2012;22:7252-5
   PubMed Web of Science ®Google Scholar
• Chemocentryx, Inc. Fused heteroaryl pyridyl and phenyl benzenesulfonamides as CCR2 modulators for the treatment of inflammation. WO2009009740; 2009
   Google Scholar
• Chemocentryx website. www.chemocentryx.com [Last accessed September 2, 2012]
   Google Scholar
• Sullivan TJ, Dairaghi DJ, Krasinski A, Characterization of CCX140-B, an orally bioavailable antagonist of the CCR2 chemokine receptor, for the treatment of type 2 diabetes and associated complications. J Pharmacol Exp Ther 2012; published online February 29, 2012; doi:10.1124/jpet.111.190918; NB: later withdrawn
   Web of Science ®Google Scholar
• Chemocentryx, Inc. Heteroaryl sulfonamides and CCR2/CCR9. US20110118248; 2011
   Google Scholar
• Chemocentryx, Inc. Aryl sulfonamides. US2006/0111351; 2006
   Google Scholar
• Walters MJ, Wang Y, Lai N, Characterization of CCX282-B, an Orally Bioavailable Antagonist of the CCR9 chemokine receptor, for treatment of inflammatory bowel disease. J Pharmacol Exp Ther 2010;335:61-9
   PubMed Web of Science ®Google Scholar
• Allergan, Inc. Sulfur derivatives as chemokine receptor modulators. WO 2012/082566; 2012
   Google Scholar
• Allergan, Inc. Phosphorus derivatives as chemokine receptor modulators. WO 2012/082568; 2012
   Google Scholar
• Allergan, Inc. Novel 1,2-bis-sulfonamide derivatives as chemokine receptor modulators. WO 2012/082633; 2012
   Google Scholar
• Allergan, Inc. CCR2 inhibitors for treating conditions of the eye. WO 2011/019679; 2011
   Google Scholar
• Proximagen LTD. 7-Hydroxy-pyrazolo[1,5-A] pyrimidine compounds and their use as CCR2 receptor antagonists. WO 2012/041817; 2012
   Google Scholar
• AstraZeneca UK Ltd. 4H-[1,2,4] Triazolo [5,1-B] pyrimidin-7-one derivatives as CCR2B receptor antagonists. WO 2011/114148; 2011
   Google Scholar
• Bristol-Myers Squibb, Inc. Cyclohexenyl modulators of chemokine receptor activity. 2010/009068; 2010
   Google Scholar
• F. Hoffman-La Roche AG. Imidazole derivatives as CCR2 receptor antagonists. WO 2009/003861; 2009
   Google Scholar
• F. Hoffman-La Roche AG. New pyrazol derivatives. WO 2009/013211; 2009
   Google Scholar
• F. Hoffman-La Roche AG. Novel heteroaryl carboxamide derivatives. WO 2009/153182; 2009
   Google Scholar
• F. Hoffman-La Roche AG. Novel biaryl derivatives. US 2009/0048238; 2009
   Google Scholar
• Boehringer Ingelheim International GMBH. Cyclic pyrimidin-4-carboxamides as CCR2 receptor antagonists for the treatment of inflammation, asthma, and COPD. WO 2010/070032; 2010
   Google Scholar
• Boehringer Ingelheim International GMBH. New CCR2 antagonists and uses thereof. WO 2011/073154; 2011
   Google Scholar
• Boehringer Ingelheim International GMBH. New CCR2 antagonists. WO 2011/151251; 2011
   Google Scholar
• Boehringer Ingelheim International GMBH. CCR2 antagonists. WO 2011/147772; 2011
   Google Scholar
• Boehringer Ingelheim International GMBH. Novel CCR2 antagonists and uses thereof. WO 2011/073155; 2011
   Google Scholar
• Boehringer Ingelheim International GMBH. CCR2 antagonists and uses thereof. WO 2011/144501; 2011
   Google Scholar
• Boehringer Ingelheim International GMBH. New CCR2 receptor antagonists, method for producing the same, and uses thereof as medicaments. WO 2011/141477; 2011
   Google Scholar
• Boehringer Ingelheim International GMBH. Novel CCR2 receptor antagonists, method for producing the same, and uses thereof as medicaments. WO 2011/141474; 2011
   Google Scholar
• Boehringer Ingelheim International GMBH. New selective CCR2 receptor antagonists. WO 2012/171863; 2012
   Google Scholar
• Ares Trading S.A. Spiroalkene carboxamide derivatives and their use as chemokine receptor modulators. WO 2012/130915; 2012
   Google Scholar
• Merck Sharp & Dohme Corp. Indole derivatives useful as CCR2 antagonists. WO 2012/125662; 2012
   Google Scholar
• Novartis Pharma GmbH. Chemokine receptor antagonists. WO 2005/077932; 2005
   Google Scholar
• Novartis AG. Aryl carboxylic acid cyclohexyl amide derivatives. WO 2008/101905; 2008
   Google Scholar
• Miltz W, Loetscher P, Janser P, Dual CCR2/CCR5 antagonists: A new approach for the treatment of autoimmune diseases and HIV infection. Pacifichem; Honolulu: 2010
   Google Scholar
• Lubin R, Yang J, Praestgaard J, Pharmacokinetic analysis of a novel CCR2/CCR5 antagonist in a randomized, double blind, placebo controlled eight ascending single dose cohort study in healthy subjects. 50th Interscience Conference on Antimicrobial Agents and Chemotherapy, Boston; 2010
   Google Scholar
• Bhalay G, Albrecht B, Akhlaq M, Design and synthesis of a library of chemokine antagonists. Bioorg Med Chem Lett 2011;21:6249-52
   PubMed Web of Science ®Google Scholar
• Lagu B, Gerchak C, Pan M, Potent and selective CC-chemokine receptor-2 (CCR2) antagonists as a potential treatment for asthma. Bioorg Med Chem Lett 2007;17:4382-6
   PubMed Web of Science ®Google Scholar
• Janssen Pharmaceutica, N.V. Synthesis of quaternary salt compounds. WO 2009/055516; 2009
   Google Scholar
• Janssen Pharmaceutica, N.V. Synthesis of quaternary salt compounds. WO 2009/055519; 2009
   Google Scholar
• Chaouk H, Draganovic D, Khanolkar V. Ophthalmic devices containing chemokine antagonists. US 2012/0004298; 2012
   Google Scholar
• Seto M, Aikawa K, Miyamoto N, Highly potent and orally active CCR5 antagonists as Anti-HIV agents: synthesis and biological activities of 1-benzazocine derivatives containing a sulfoxide moiety. J Med Chem 2006;49:2037-48
   PubMed Web of Science ®Google Scholar
• Lalezari J, Gathe J, Brinson C, Safety, efficacy, and pharmokinetics of TBR-652, a CCR5/2 antagonist, in HIV-1-infected, treatment-experienced, CCR5 antagonist-naive subjects. J Acquir Immune Defic Syndr 2001;57:118-25
   Google Scholar
• Berkhout TA, Blaney FE, Bridges AM, CCR2: characterization of the antagonist binding site from a combined receptor modeling/mutagenesis approach. J Med Chem 2003;46:4070-86
   PubMed Web of Science ®Google Scholar
• Mirzadegan T, Diehl F, Ebi B, 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
   PubMed Web of Science ®Google Scholar
• Wu B, Chien EY, Mol CD, Structures of the CXCR4 chemokine GPCR with small-molecule and cyclic peptide antagonists. Science 2010;330:1066-71
   PubMed Web of Science ®Google Scholar
• de Kruijf P, Lim HD, Roumen L, Identification of a novel allosteric binding site in the CXCR2 chemokine receptor. Mol Pharmacol 2011;80:1108-18
   PubMed Web of Science ®Google Scholar
• Scholten DJ, Canals M, Maussang D, Pharmacological modulation of chemokine receptor function. Br J Pharmacol 2012;165:1617-43
   PubMed Web of Science ®Google Scholar
• Kenakin T. G protein coupled receptors as allosteric proteins and the role of allosteric modulators. J Recept Signal Transduct Res 2010;30:313-21
   PubMed Web of Science ®Google Scholar
• Sohy D, Yano H, de Nadai P, Hetero-oligomerization of CCR2, CCR5, and CXCR4 and the protean effects of "selective" antagonists. J Biol Chem 2009;284:31270-9
   PubMed Web of Science ®Google Scholar
• Schall TJ, Proudfoot AEI. Overcoming hurdles in developing successful drugs targeting chemokine receptors. Nat Rev Immunology 2011;11:355-63
   PubMed Web of Science ®Google Scholar
• Haringman JJ, Gerlag DM, Smeets TJ, A randomized controlled trial with an anti-CCL2 (anti-monocyte chemotactic protein 1) monoclonal antibody in patients with rheumatoid arthritis. Arthritis Rheum 2006;54:2387-92
   PubMed Web of Science ®Google Scholar
• Hanefeld M, Schell E, Gouni-Berthold I, Oral chemokine receptor 2 antagonist CCX140-B shows safety and efficacy in type 2 diabetes mellitus. Diabetes 2011a;60(I):A85
   Google Scholar
• Quinones MP, Estrada CA, Kalkonde Y, The complex role of the chemokine receptor CCR2 in collagen-induced arthritis: implications for therapeutic targeting of CCR2 in rheumatoid arthritis. J Mol Med (Berl) 2005;83:672-81
   PubMed Web of Science ®Google Scholar
• Lebre MC, Vergunst CE, Choi IY, Why CCR2 and CCR5 blockade failed and why CCR1 blockade might still be effective in the treatment of rheumatoid arthritis. PLoS One 2011;6:e21772
   PubMed Web of Science ®Google Scholar