Chemokine receptor antagonists: Part 2

Expert Opinion on Therapeutic Patents

Volumn 19, Issue 2, 2009, Pages 199-221

  Pease, James E ^a   Horuk, Richard ^b  

^a NATIONAL HEART AND LUNG INSTITUTE   (United Kingdom)

^b TOURO UNIVERSITY CALIFORNIA   (United States)

Author keywords

Antagonism; Chemokine receptors; Chemokines; GPCRs

Indexed keywords

1 ACETYL N [3 [4 (4 CARBAMOYLBENZYL) 1 PIPERIDINYL]PROPYL] N (3 CHLORO 4 METHYLPHENYL) 4 PIPERIDINECARBOXAMIDE; 4 [(4 BROMOPHENYL)(ETHOXYIMINO)METHYL] 1' [(2,4 DIMETHYL 3 PYRIDINYL)CARBONYL] 4' METHYL 1,4' BIPIPERIDINE; 8 [4 (2 BUTOXYETHOXY)PHENYL] 1,2,3,4 TETRAHYDRO 1 ISOBUTYL N [4 (1 PROPYL 1H IMIDAZOL 5 YLMETHYLSULFINYL)PHENYL] 1 BENZAZOCINE 5 CARBOXAMIDE; AMG 487; APLAVIROC; CCX 282; CHEMOKINE RECEPTOR ANTAGONIST; CHEMOKINE RECEPTOR CCR5 ANTAGONIST; CHEMOKINE RECEPTOR CXCR4 ANTAGONIST; CYCLOSPORIN A; E 913; GW 873410; IMIDAZOLE DERIVATIVE; INCB 9471; KRH 1636; LMD 009; MARAVIROC; N [4 [[[6,7 DIHYDRO 2 (4 METHYLPHENYL) 5H BENZOCYCLOHEPTEN 8 YL]CARBONYL]AMINO]BENZYL] N,N DIMETHYL 2H TETRAHYDROPYRAN 4 AMINIUM CHLORIDE; NIBR 1282; OLANZAPINE; PIPERIDINE DERIVATIVE; PLERIXAFOR; SB 649701; SCH 350634; UCB 35625; UNCLASSIFIED DRUG; UNINDEXED DRUG; VICRIVIROC; WZ 811; YM 344484; ZK 756326;

ACQUIRED IMMUNE DEFICIENCY SYNDROME; BIPOLAR DISORDER; CARDIOVASCULAR DISEASE; CLINICAL TRIAL; COMPETITIVE INHIBITION; CROHN DISEASE; DRUG ABSORPTION; DRUG BINDING; DRUG BIOAVAILABILITY; DRUG CLEARANCE; DRUG DESIGN; DRUG HALF LIFE; DRUG METABOLISM; DRUG SCREENING; DRUG STRUCTURE; HIGH THROUGHPUT SCREENING; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1; IC 50; LIVER CANCER; LIVER TOXICITY; NONHUMAN; PHARMACOPHORE; QT PROLONGATION; REVIEW; SCHIZOPHRENIA; STRUCTURE ACTIVITY RELATION;

ANIMALS; DRUG DELIVERY SYSTEMS; HUMANS; PATENTS AS TOPIC; RECEPTORS, CCR; RECEPTORS, CCR5; RECEPTORS, CCR8; RECEPTORS, CXCR3; RECEPTORS, CXCR4;

EID: 67649341169     PISSN: 13543776     EISSN: None     Source Type: Journal    
DOI: 10.1517/13543770802641353     Document Type: Review

References (144)

1. Pease JE, Horuk R. Chemokine receptor antagonists:Part 1. Expert Opin Ther Pat 2009
2. Samson M, Labbe O, Mollereau C, et al. Molecular cloning and functional expression of a new human CC-chemokine receptor gene. Biochemistry 1996;35:3362-3367 (Pubitemid 26092558)
3. Valentin A, Rosati M, Patenaude DJ, et al. Persistent HIV-1 infection of natural killer cells in patients receiving highly active antiretroviral therapy. Proc Natl Acad Sci USA 2002;99:7015-7020 (Pubitemid 34526249)
4. Campbell JJ, Brightling CE, Symon FA, et al. Expression of chemokine receptors by lung T cells from normal and asthmatic subjects. J Immunol 2001;166:2842-2848 (Pubitemid 32173526)
5. Loetscher P, Uguccioni M, Bordoli L, et al. CCR5 is characteristic of Th1 lymphocytes. Nature 1998;391:344-345 (Pubitemid 28093499)
6. Sallusto F, Lenig D, Mackay CR, Lanzavecchia A. Flexible programs of chemokine receptor expression on human polarized T helper 1 and 2 lymphocytes. J Exp Med 1998;187:875-883 (Pubitemid 28141661)
7. Tacke F, Alvarez D, Kaplan TJ, et al. Monocyte subsets differentially employ CCR2, CCR5, and CX3CR1 to accumulate within atherosclerotic plaques. J Clin Invest 2007;117:185-194 (Pubitemid 46048465)
8. Segerer S, Cui Y, Eitner F, et al. Expression of chemokines and chemokine receptors during human renal transplant rejection. Am J Kidney Dis 2001;37:518-531 (Pubitemid 32195291)
9. Goddard S, Williams A, Morland C, et al. Differential expression of chemokines and chemokine receptors shapes the inflammatory response in rejecting human liver transplants. Transplantation 2001;72:1957-1967 (Pubitemid 34027871)
10. Matsuzaki K, Hokari R, Kato S, et al. Differential expression of CCR5 and CRTH2 on infiltrated cells in colonic mucosa of patients with ulcerative colitis. J Gastroenterol Hepatol 2003;18:1081-1088 (Pubitemid 37175951)
11. Wedderburn LR, Robinson N, Patel A, et al. Selective recruitment of polarized T cells expressing CCR5 and CXCR3 to the inflamed joints of children with juvenile idiopathic arthritis. Arthritis Rheum 2000;43:765-774 (Pubitemid 30677567)
12. 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;159:1701-1710 (Pubitemid 33062513)
13. Moore JP, Trkola A, Dragic T. Co-receptors for HIV-1 entry. Curr Opin Immunol 1997;9:551-562 (Pubitemid 27390052)
14. Baba M, Nishimura O, Kanzaki N, et al. A small-molecule, nonpeptide CCR5 antagonist with highly potent and selective anti-HIV-1 activity. Proc Natl Acad Sci USA 1999;96:5698-5703 (Pubitemid 29234681)
15. Shiraishi M, Aramaki Y, Seto M, et al. Discovery of novel, potent, and selective small-molecule CCR5 antagonists as anti-HIV-1 agents: synthesis and biological evaluation of anilide derivatives with a quaternary ammonium moiety. J Med Chem 2000;43:2049-2063 (Pubitemid 30340944)
16. Imamura S, Kurasawa O, Nara Y, et al. CCR5 antagonists as anti-HIV-1 agents. Part 2: Synthesis and biological evaluation of N-[3-(4-benzylpiperidin- 1-yl)propyl]- N,N′-diphenylureas. Bioorg Med Chem 2004;12:2295-2306
17. Imamura S, Nishikawa Y, Ichikawa T, et al. CCR5 antagonists as anti-HIV-1 agents. Part 3: Synthesis and biological evaluation of piperidine-4-carboxamide derivatives. Bioorg Med Chem 2005;13:397-416
18. Imamura S, Ichikawa T, Nishikawa Y, et al. Discovery of a piperidine-4-carboxamide CCR5 antagonist (TAK-220) with highly potent Anti-HIV-1 activity. J Med Chem 2006;49:2784-2793
19. Seto M, Aikawa K, Miyamoto N, et al. Highly potent and orally active CCR5 antagonists as anti-HIV-1 agents: synthesis and biological activities of 1-benzazocine derivatives containing a sulfoxide moiety. J Med Chem 2006;49:2037-2048
20. Dorn CP, Finke PE, Oates B, et al. Antagonists of the human CCR5 receptor as anti-HIV-1 agents. Part 1: discovery and initial structure-activity relationships for 1-amino-2-phenyl-4-(piperidin-1-yl) butanes. Bioorg Med Chem Lett 2001;11:259-264
21. Finke PE, Meurer LC, Oates B, et al. Antagonists of the human CCR5 receptor as anti-HIV-1 agents. Part 2: structure-activity relationships for substituted 2-Aryl-1-[N-(methyl)-N-(phenylsulfonyl)amino]-4-(piperidin-1-yl) butanes. Bioorg Med Chem Lett 2001;11:265-270
22. Finke PE, Meurer LC, Oates B, et al. Antagonists of the human CCR5 receptor as anti-HIV-1 agents. Part 3: a proposed pharmacophore model for 1-[N-(methyl)-N-(phenylsulfonyl)amino]-2-(phenyl)-4-[4-(substituted) piperidin-1-yl]butanes. Bioorg Med Chem Lett 2001;11:2469-2473
23. Finke PE, Oates B, Mills SG, et al. Antagonists of the human CCR5 receptor as anti-HIV-1 agents. Part 4: synthesis and structure-activity relationships for 1-[N-(methyl)-N-(phenylsulfonyl) amino]-2-(phenyl)-4-(4-(N- (alkyl)-N-(benzyloxycarbonyl)amino)piperidin-1-yl) butanes. Bioorg Med Chem Lett 2001;11:2475-2479
24. Kim D, Wang L, Caldwell CG, et al. Discovery of human CCR5 antagonists containing hydantoins for the treatment of HIV-1 infection. Bioorg Med Chem Lett 2001;11:3099-3102 (Pubitemid 33092001)
25. Kim D, Wang L, Caldwell CG, et al. Design, synthesis, and SAR of heterocycle-containing antagonists of the human CCR5 receptor for the treatment of HIV-1 infection. Bioorg Med Chem Lett 2001;11:3103-3106 (Pubitemid 33092002)
26. Hale JJ, Budhu RJ, Holson EB, et al. 1,3,4-Trisubstituted pyrrolidine CCR5 receptor antagonists. Part 2: lead optimization affording selective, orally bioavailable compounds with potent anti-HIV activity. Bioorg Med Chem Lett 2001;11:2741-2745
27. Hale JJ, Budhu RJ, Mills SG, et al. 1,3,4-Trisubstituted pyrrolidine CCR5 receptor antagonists. Part 1: discovery of the pyrrolidine scaffold and determination of its stereochemical requirements. Bioorg Med Chem Lett 2001;11:1437-1440
28. Hale JJ, Budhu RJ, Mills SG, et al. 1,3,4-Trisubstituted pyrrolidine CCR5 receptor antagonists. Part 3: polar functionality and its effect on anti-HIV-1 activity. Bioorg Med Chem Lett 2002;12:2997-3000
29. Willoughby CA, Rosauer KG, Hale JJ, et al. 1,3,4 trisubstituted pyrrolidine CCR5 receptor antagonists bearing 4-aminoheterocycle substituted piperidine side chains. Bioorg Med Chem Lett 2003;13:427-431
30. Shen DM, Shu M, Mills SG, et al. Antagonists of human CCR5 receptor containing 4-(pyrazolyl)piperidine side chains. Part 1: Discovery and SAR study of 4-pyrazolylpiperidine side chains. Bioorg Med Chem Lett 2004;14:935-939
31. Shen DM, Shu M, Willoughby CA, et al. Antagonists of human CCR5 receptor containing 4-(pyrazolyl)piperidine side chains. Part 2: Discovery of potent, selective, and orally bioavailable compounds. Bioorg Med Chem Lett 2004;14:941-945
32. Shu M, Loebach JL, Parker KA, et al. Antagonists of human CCR5 receptor containing 4-(pyrazolyl)piperidine side chains. Part 3: SAR studies on the benzylpyrazole segment. Bioorg Med Chem Lett 2004;14:947-952
33. Tagat JR, McCombie SW, Steensma RW, et al. Piperazine-based CCR5 antagonists as HIV-1 inhibitors. I: 2(S)-methyl piperazine as a key pharmacophore element. Bioorg Med Chem Lett 2001;11:2143-2146
34. Tagat JR, Steensma RW, McCombie SW, et al. Piperazine-based CCR5 antagonists as HIV-1 inhibitors. II. Discovery of 1-[(2,4-dimethyl-3-pyridinyl) carbonyl]-4- methyl-4-[3(S)-methyl-4-[1(S)- [4-(trifluoromethyl)phenyl] ethyl]-1-piperazinyl]-piperidine N1-oxide (Sch-350634), an orally bioavailable, potent CCR5 antagonist. J Med Chem 2001;44:3343-3346
35. McCombie SW, Tagat JR, Vice SF, et al. Piperazine-based CCR5 antagonists as HIV-1 inhibitors. III: synthesis, antiviral and pharmacokinetic profiles of symmetrical heteroaryl carboxamides. Bioorg Med Chem Lett 2003;13:567-571
36. Strizki JM, Xu S, Wagner NE, et al. 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 2001;98:12718-12723 (Pubitemid 33020012)
37. Palani A, Shapiro S, Clader JW, et al. 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 2001;44:3339-3342
38. Este JA. Sch-351125 and Sch-350634. Schering-Plough. Curr Opin Investig Drugs 2002;3:379-383
39. Tagat JR, McCombie SW, Nazareno D, et al. Piperazine-based CCR5 antagonists as HIV-1 inhibitors. IV. Discovery of 1-[(4,6-dimethyl-5- pyrimidinyl) carbonyl]-4-[4-[2-methoxy-1(R)-4-(trifluoromethyl)phenyl]ethyl-3(S) -methyl- 1-piperaz inyl]-4-methylpiperidine (Sch-417690/Sch-D), a potent, highly selective, and orally bioavailable CCR5 antagonist. J Med Chem 2004;47:2405-2408
40. Gulick RM, Su Z, Flexner C, et al. Phase 2 study of the safety and efficacy of vicriviroc, a CCR5 inhibitor, in HIV-1-Infected, treatment-experienced patients: AIDS clinical trials group 5211. J Infect Dis 2007;196:304-312 (Pubitemid 47047471)
41. Thoma G, Nuninger F, Schaefer M, et al. Orally bioavailable competitive CCR5 antagonists. J Med Chem 2004;47:1939-1955 (Pubitemid 38453913)
42. Thoma G, Beerli C, Bigaud M, et al. Reduced cardiac side-effect potential by introduction of polar groups: discovery of NIBR-1282, an orally bioavailable CCR5 antagonist which is active in vivo. Bioorg Med Chem Lett 2008;18:2000-2005
43. Burrows JN, Cumming JG, Fillery SM, et al. Modulators of the human CCR5 receptor. Part 1: Discovery and initial SAR of 1-(3,3-diphenylpropyl)- piperidinyl amides and ureas. Bioorg Med Chem Lett 2005;15:25-28
44. Cumming JG, Cooper AE, Grime K, et al. Modulators of the human CCR5 receptor. Part 2: SAR of substituted 1-(3,3-diphenylpropyl)-piperidinyl phenylacetamides. Bioorg Med Chem Lett 2005;15:5012-5015
45. Cumming JG, Brown SJ, Cooper AE, et al. Modulators of the human CCR5 receptor. Part 3: SAR of substituted 1-[3-(4-methanesulfonylphenyl)-3- phenylpropyl]-piperidinyl phenylacetamides. Bioorg Med Chem Lett 2006;16:3533-3536
46. Wei RG, Arnaiz DO, Chou YL, et al. CCR5 receptor antagonists: discovery and SAR study of guanylhydrazone derivatives. Bioorg Med Chem Lett 2007;17:231-234 (Pubitemid 44959956)
47. Lu SF, Chen B, Davey D, et al. CCR5 receptor antagonists: discovery and SAR of novel 4-hydroxypiperidine derivatives. Bioorg Med Chem Lett 2007;17:1883-1887 (Pubitemid 46367684)
48. Maeda K, Yoshimura K, Shibayama S, et al. Novel low molecular weight spirodiketopiperazine derivatives potently inhibit R5 HIV-1 infection through their antagonistic effects on CCR5. J Biol Chem 2001;276:35194-35200 (Pubitemid 37384528)
49. Nishizawa R, Nishiyama T, Hisaichi K, et al. Spirodiketopiperazine-based CCR5 antagonists: Lead optimization from biologically active metabolite. Bioorg Med Chem Lett 2007;17:727-731 (Pubitemid 46127639)
50. Maeda K, Nakata H, Koh Y, et al. Spirodiketopiperazine-based CCR5 inhibitor which preserves CC-chemokine/CCR5 interactions and exerts potent activity against R5 human immunodeficiency virus type 1 in vitro. J Virol 2004;78:8654-8662 (Pubitemid 39025131)
51. Ryan CT. Trials of aplaviroc halted in treatment-naive patients. AIDS Clin Care 2005;17:107-108
52. Nichols WG, Steel HM, Bonny T, et al. Hepatotoxicity observed in clinical trials of aplaviroc (GW873140). Antimicrob Agents Chemother 2008;52:858-865 (Pubitemid 351358363)
53. Shin N, Solomon K, Wang K, et al. INCB9471 Is a Non-Competitive Small Molecule Antagonist of CCR5 [Poster 751]. 47th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy. Chicago; 2007
54. Armour D, de Groot MJ, Edwards M, et al. The discovery of CCR5 receptor antagonists for the treatment of HIV infection: hit-to-lead studies. ChemMedChem 2006;1:706-709 (Pubitemid 44154358)
55. Lieberman-Blum SS, Fung HB, Bandres JC. Maraviroc: a CCR5-receptor antagonist for the treatment of HIV-1 infection. Clin Ther 2008;30:1228-1250
56. Tiffany HL, Lautens LL, Gao JL, et al. Identification of CCR8: a human monocyte and thymus receptor for the CC chemokine I-309. J Exp Med 1997;186:165-170 (Pubitemid 27304860)
57. Roos RS, Loetscher M, Legler DF, et al. Identification of CCR8, the receptor for the human CC chemokine I-309. J Biol Chem 1997;272:17251-17254 (Pubitemid 27311146)
58. Kremer L, Carramolino L, Goya I, et al. The transient expression of C-C chemokine receptor 8 in thymus identifies a thymocyte subset committed to become CD4(+) single-positive T cells. J Immunol 2001;166:218-225 (Pubitemid 32038435)
59. Napolitano M, Zingoni A, Bernardini G, et al. Molecular cloning of TER1, a chemokine receptor-like gene expressed by lymphoid tissues. J Immunol 1996;157:2759-2763 (Pubitemid 126450027)
60. Zaballos A, Varona R, Gutierrez J, et al. Molecular cloning and RNA expression of two new human chemokine receptor-like genes. Biochem Biophys Res Commun 1996;227:846-853 (Pubitemid 26387814)
61. Bonecchi R, Bianchi G, Bordignon PP, et al. Differential Expression of Chemokine Receptors and Chemotactic Responsiveness of Type 1 T Helper Cells (Th1s) and Th2s. J Exp Med 1998;187:129-134 (Pubitemid 28044828)
62. Zingoni A, Soto H, Hedrick JA, et al. The chemokine receptor CCR8 is preferentially expressed in Th2 but not Th1 cells. J Immunol 1998;161:547-551 (Pubitemid 28323513)
63. Montes-Vizuet R, Vega-Miranda A, Valencia-Maqueda E, et al. CC chemokine ligand 1 is released into the airways of atopic asthmatics. Eur Respir J 2006;28:59-67 (Pubitemid 44914261)
64. Panina-Bordignon P, Papi A, Mariani M, et al. The C-C chemokine receptors CCR4 and CCR8 identify airway T cells of allergen-challenged atopic asthmatics. J Clin Invest 2001;107:1357-1364 (Pubitemid 32522029)
65. Gombert M, Dieu-Nosjean MC, Winterberg F, et al. CCL1-CCR8 interactions: an axis mediating the recruitment of T cells and Langerhans-type dendritic cells to sites of atopic skin inflammation. J Immunol 2005;174:5082-5091 (Pubitemid 40504594)
66. Qu C, Edwards EW, Tacke F, et al. Role of CCR8 and other chemokine pathways in the migration of monocyte-derived dendritic cells to lymph nodes. J Exp Med 2004;200:1231-1241 (Pubitemid 39552565)
67. Sebastiani S, Allavena P, Albanesi C, et al. Chemokine receptor expression and function in CD4+ T lymphocytes with regulatory activity. J Immunol 2001;166:996-1002 (Pubitemid 32060256)
68. Cantor J, Haskins K. Recruitment and activation of macrophages by pathogenic CD4 T cells in type 1 diabetes: evidence for involvement of CCR8 and CCL1. J Immunol 2007;179:5760-5767
69. Jin J, Wang Y, Wang F, et al. Oxazolidinones as novel human CCR8 antagonists. Bioorg Med Chem Lett 2007;17:1722-1725 (Pubitemid 46298689)
70. Marro ML, Daniels DA, Andrew DP, et al. In vitro selection of RNA aptamers that block CCL1 chemokine function. Biochem Biophys Res Commun 2006;349:270-276
71. Jenkins TJ, Guan B, Dai M, et al. Design, synthesis, and evaluation of naphthalene-sulfonamide antagonists of human CCR8. J Med Chem 2007;50:566-584 (Pubitemid 46239790)
72. Ghosh S, Elder A, Guo J, et al. Design, synthesis, and progress toward optimization of potent small molecule antagonists of CC chemokine receptor 8 (CCR8). J Med Chem 2006;49:2669-2672
73. Haskell CA, Horuk R, Liang M, et al. Identification and Characterization of a Potent, Selective Non-Peptide Agonist of the CC Chemokine Receptor CCR8. Mol Pharmacol 2006;69:309-316
74. Jensen PC, Nygaard R, Thiele S, et al. Molecular interaction of a potent nonpeptide agonist with the chemokine receptor CCR8. Mol Pharmacol 2007;72:327-340 (Pubitemid 47124113)
75. Zabel BA, Agace WW, Campbell JJ, et al. Human G protein-coupled receptor GPR-9-6/CC chemokine receptor 9 is selectively expressed on intestinal homing T lymphocytes, mucosal lymphocytes, and thymocytes and is required for thymus-expressed chemokine-mediated chemotaxis. J Exp Med 1999;190:1241-1256 (Pubitemid 29522208)
76. Wurbel MA, Philippe JM, Nguyen C, et al. The chemokine TECK is expressed by thymic and intestinal epithelial cells and attracts double- and single-positive thymocytes expressing the TECK receptor CCR9. Eur J Immunol 2000;30:262-271 (Pubitemid 30011788)
77. Saruta M, Yu QT, Avanesyan A, et al. Phenotype and effector function of CC chemokine receptor 9-expressing lymphocytes in small intestinal Crohn's disease. J Immunol 2007;178:3293-3300 (Pubitemid 46333214)
78. Wei Z, Ertl L, Baumgart T, et al. TRAFICET-ENTM, a highly potent and selectuve antagonist of CCR9, ameliorates experimental ileitis and colitis. Dig Dis Sci 2005;50:1969
79. Busch-Petersen J, Wang Y. Phenol-containg antagonists of the CXCR2 receptor. Expert Opin Ther Patents 2008;18:629-637
80. Murphy PM, Baggiolini M, Charo IF, et al. International union of pharmacology. XXII. Nomenclature for chemokine receptors. Pharmacol Rev 2000;52:145-176
81. Hancock WW, Lu B, Gao W, et al. Requirement of the chemokine receptor CXCR3 for acute allograft rejection. J Exp Med 2000;192:1515-1520 (Pubitemid 30953889)
82. Flier J, Boorsma DM, van Beek PJ, et al. Differential expression of CXCR3 targeting chemokines CXCL10, CXCL9, and CXCL11 in different types of skin inflammation. J Pathol 2001;194:398-405 (Pubitemid 32782663)
83. Xie JH, Nomura N, Lu M, et al. Antibody-mediated blockade of the CXCR3 chemokine receptor results in diminished recruitment of T helper 1 cells into sites of inflammation. J Leukoc Biol 2003;73:771-780 (Pubitemid 38040456)
84. Johnson M, Li AR, Liu J, et al. Discovery and optimization of a series of quinazolinone-derived antagonists of CXCR3. Bioorg Med Chem Lett 2007;17:3339-3343 (Pubitemid 46819037)
85. Du X, Chen X, Mihalic JT, et al. Design and optimization of imidazole derivatives as potent CXCR3 antagonists. Bioorg Med Chem Lett 2008;18:608-613
86. Li AR, Johnson MG, Liu J, et al. Optimization of the heterocyclic core of the quinazolinone-derived CXCR3 antagonists. Bioorg Med Chem Lett 2008;18:688-693
87. Ribeiro S, Horuk R. Chemokine receptor antagonists from the bench to the clinic. In: Hannan A, Engelhardt B, editors, Weinheim: Wiley-VCH; 2005
88. Allen DR, Bolt A, Chapman GA, et al. Identification and structure-activity relationships of 1-aryl-3-piperidin-4-yl-urea derivatives as CXCR3 receptor antagonists. Bioorg Med Chem Lett 2007;17:697-701 (Pubitemid 46131425)
89. Watson RJ, Allen DR, Birch HL, et al. Development of CXCR3 antagonists. Part 2: Identification of 2-amino(4-piperidinyl) azoles as potent CXCR3 antagonists. Bioorg Med Chem Lett 2007;17:6806-6810
90. Watson RJ, Allen DR, Birch HL, et al. Development of CXCR3 antagonists. Part 3: Tropenyl and homotropenyl-piperidine urea derivatives. Bioorg Med Chem Lett 2008;18:147-151
91. Knight RL, Allen DR, Birch HL, et al. Development of CXCR3 antagonists. Part 4: discovery of 2-amino-(4-tropinyl) quinolines. Bioorg Med Chem Lett 2008;18:629-633
92. Cole AG, Stroke IL, Brescia MR, et al. Identification and initial evaluation of 4-N-aryl-[1,4]diazepane ureas as potent CXCR3 antagonists. Bioorg Med Chem Lett 2006;16:200-203
93. Hayes ME, Wallace GA, Grongsaard P, et al. Discovery of small molecule benzimidazole antagonists of the chemokine receptor CXCR3. Bioorg Med Chem Lett 2008;18:1573-1576 (Pubitemid 351318258)
94. Hayes ME, Breinlinger EC, Wallace GA, et al. Lead identification of 2-iminobenzimidazole antagonists of the chemokine receptor CXCR3. Bioorg Med Chem Lett 2008;18:2414-2419
95. Bongartz JP, Buntinx M, Coesemans E, et al. Synthesis and structure-activity relationship of benzetimide derivatives as human CXCR3 antagonists. Bioorg Med Chem Lett 2008; In press
96. Choudhary MS, Sachs N, Uluer A, et al. Differential ergoline and ergopeptine binding to 5-hydroxytryptamine2A receptors: ergolines require an aromatic residue at position 340 for high affinity binding. Mol Pharmacol 1995;47:450-457
97. Baentli R, Glivkman F, Kovaril J, et al. Ergoline derivatives and their use as chemokine receptor ligands. WO2006128658; 2006
98. Kim SH, Anilkumar GN, Wong MKC, et al. Heterocyclic substituted piperazines with CXCR3 antagonist activity. WO2006088837; 2006
99. Rosenblum SB, Kozlowski JA, Shih N, et al. Heterocyclic substituted pyridine compounds with CXCR3 antagonist activity. WO2007109238; 2007
100. Axten JM, Foley JJ, Kingsbury WD, Sarau HM. Imidazolium CXCR3 inhibitors. WO03101970; 2003
101. Verzijl D, Storelli S, Scholten DJ, et al. Noncompetitive antagonism and inverse agonism as mechanism of action of nonpeptidergic antagonists at primate and rodent CXCR3 chemokine receptors. J Pharmacol Exp Ther 2008;325:544-555 (Pubitemid 351574793)
102. Bleul CC, Wu L, Hoxie JA, et al. The HIV coreceptors CXCR4 and CCR5 are differentially expressed and regulated on human T lymphocytes. Proc Natl Acad Sci USA 1997;94:1925-1930 (Pubitemid 27113938)
103. Forster R, Kremmer E, Schubel A, et al. Intracellular and surface expression of the HIV-1 coreceptor CXCR4/fusin on various leukocyte subsets: rapid internalization and recycling upon activation. J Immunol 1998;160:1522-1531 (Pubitemid 28093457)
104. Hori T, Sakaida H, Sato A, et al. Detection and delineation of CXCR-4 (fusin) as an entry and fusion cofactor for T cell-tropic HIV-1 by three different monoclonal antibodies. J Immunol 1998;160:180-188 (Pubitemid 28116728)
105. Loetscher M, Geiser T, O'Reilly T, et al. Cloning of a human seven-transmembrane domain receptor, LESTR, that is highly expressed in leukocytes. J Biol Chem 1994;269:232-237 (Pubitemid 24026649)
106. Oberlin E, Amara A, Bachelerie F, et al. The CXC chemokine SDF-1 is the ligand for LESTR/fusin and prevents infection by T-cell-line-adapted HIV-1. Nature 1996;382:833-835 (Pubitemid 26299571)
107. Bleul CC, Farzan M, Choe H, et al. The lymphocyte chemoattractant SDF-1 is a ligand for LESTR/fusin and blocks HIV-1 entry. Nature 1996;382:829-833 (Pubitemid 26299570)
108. De Clercq E, Yamamoto N, Pauwels R, et al. Potent and selective inhibition of human immunodeficiency virus (HIV)-1 and HIV-2 replication by a class of bicyclams interacting with a viral uncoating event. Proc Natl Acad Sci USA 1992;89:5286-5290
109. Gerlach LO, Skerlj RT, Bridger GJ, Schwartz TW. Molecular interactions of cyclam and bicyclam non-peptide antagonists with the CXCR4 chemokine receptor. J Biol Chem 2001;276:14153-14160 (Pubitemid 37391801)
110. Rosenkilde MM, Gerlach LO, Jakobsen JS, et al. Molecular mechanism of AMD3100 antagonism in the CXCR4 receptor: transfer of binding site to the CXCR3 receptor. J Biol Chem 2004;279:3033-3041 (Pubitemid 38114296)
111. Hatse S, Princen K, Gerlach LO, et al. Mutation of Asp(171) and Asp(262) of the chemokine receptor CXCR4 impairs its coreceptor function for human immunodeficiency virus-1 entry and abrogates the antagonistic activity of AMD3100. Mol Pharmacol 2001;60:164-173
112. Hendrix CW, Collier AC, Lederman MM, et al. Safety, pharmacokinetics, and antiviral activity of AMD3100, a selective CXCR4 receptor inhibitor, in HIV-1 infection. J Acquir Immune Defic Syndr 2004;37:1253-1262 (Pubitemid 39281506)
113. Aiuti A, Webb IJ, Bleul C, et al. The chemokine SDF-1 is a chemoattractant for human CD34+ hematopoietic progenitor cells and provides a new mechanism to explain the mobilization of CD34+ progenitors to peripheral blood. J Exp Med 1997;185:111-120 (Pubitemid 27039446)
114. Peled A, Grabovsky V, Habler L, et al. The chemokine SDF-1 stimulates integrin-mediated arrest of CD34(+) cells on vascular endothelium under shear flow. J Clin Invest 1999;104:1199-1211 (Pubitemid 29536291)
115. Broxmeyer HE, Orschell CM, Clapp DW, et al. Rapid mobilization of murine and human hematopoietic stem and progenitor cells with AMD3100, a CXCR4 antagonist. J Exp Med 2005;201:1307-1318 (Pubitemid 40629073)
116. Martin C, Bridger GJ, Rankin SM. Structural analogues of AMD3100 mobilise haematopoietic progenitor cells from bone marrow in vivo according to their ability to inhibit CXCL12 binding to CXCR4 in vitro. Br J Haematol 2006;134:326-329 (Pubitemid 43990796)
117. Devine SM, Flomenberg N, Vesole DH, et al. Rapid mobilization of CD34+ cells following administration of the CXCR4 antagonist AMD3100 to patients with multiple myeloma and non-Hodgkin's lymphoma. J Clin Oncol 2004;22:1095-1102 (Pubitemid 41095043)
118. Liles WC, Rodger E, Broxmeyer HE, et al. Augmented mobilization and collection of CD34+ hematopoietic cells from normal human volunteers stimulated with granulocyte-colony-stimulating factor by single-dose administration of AMD3100, a CXCR4 antagonist. Transfusion 2005;45:295-300 (Pubitemid 40389423)
119. Holtan SG, Porrata LF, Micallef IN, et al. AMD3100 affects autograft lymphocyte collection and progression-free survival after autologous stem cell transplantation in non-Hodgkin lymphoma. Clin Lymphoma Myeloma 2007;7:315-318 (Pubitemid 46408198)
120. Murakami T, Nakajima T, Koyanagi Y, et al. A small molecule CXCR4 inhibitor that blocks T cell line-tropic HIV-1 infection. J Exp Med 1997;186:1389-1393 (Pubitemid 27469035)
121. Ichiyama K, Yokoyama-Kumakura S, Tanaka Y, et al. A duodenally absorbable CXC chemokine receptor 4 antagonist, KRH-1636, exhibits a potent and selective anti-HIV-1 activity. Proc Natl Acad Sci USA 2003;100:4185-4190 (Pubitemid 36418178)
122. Zhan W, Liang Z, Zhu A, et al. Discovery of small molecule CXCR4 antagonists. J Med Chem 2007;50:5655-5664 (Pubitemid 350106020)
123. Valks GC, McRobbie G, Lewis EA, et al. Configurationally restricted bismacrocyclic CXCR4 receptor antagonists. J Med Chem 2006;49:6162-6165 (Pubitemid 44595193)
124. Available from: http://www.polyphor.com/
125. Pease JE, Horuk R. CCR1 antagonists in clinical development. Expert Opin Investig Drugs 2005;14:785-796 (Pubitemid 41030947)
126. Ribeiro S, Horuk R. The clinical potential of chemokine receptor antagonists. Pharmacol Ther 2005;107:44-58 (Pubitemid 40803508)
127. Roche O, Schneider P, Zuegge J, et al. Development of a virtual screening method for identification of "frequent hitters" in compound libraries. J Med Chem 2002;45:137-142
128. Schnickel GT, Bastani S, Hsieh GR, et al. Combined CXCR3/CCR5 blockade attenuates acute and chronic rejection. J Immunol 2008;180:4714-4721
129. Suzuki K, Morokata T, Morihira K, et al. A dual antagonist for chemokine CCR3 receptor and histamine H1 receptor. Eur J Pharmacol 2007;563:224-232 (Pubitemid 46602231)
130. Simons FE, Simons KJ. The pharmacology and use of H1-receptor-antagonist drugs. N Engl J Med 1994;330:1663-1670 (Pubitemid 24166868)
131. Vaidehi N, Schlyer S, Trabanino RJ, et al. Predictions of CCR1 chemokine receptor structure and BX 471 antagonist binding followed by experimental validation. J Biol Chem 2006;281:27613-27620 (Pubitemid 44401786)
132. Barnes PJ. Inhaled glucocorticoids for asthma. N Engl J Med 1995;332:868-875
133. 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;280:4808-4816
134. Vedani A, Dobler M, Dollinger H, et al. Novel ligands for the chemokine receptor-3 (CCR3): a receptor-modeling study based on 5D-QSAR. J Med Chem 2005;48:1515-1527 (Pubitemid 40364559)
135. 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 (Pubitemid 41672734)
136. 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;275:25985-25992 (Pubitemid 30676638)
137. Naya A, Kobayashi K, Ishikawa M, et al. Discovery of a novel CCR3 selective antagonist. Bioorg Med Chem Lett 2001;11:1219-1223 (Pubitemid 32406089)
138. 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;17:4382-4386 (Pubitemid 47021372)
139. Hersperger R, Janser P, Pfenninger E, et al. Chemokine receptor antagonists. US20070155721; 2007
140. Miltz W. Dual CCR2/CCR5 Antagonists: A New Approach for the Treatment of Autoimmune Diseases. ACS meeting 2008, April 6-10, New Orleans, Louisiana. Available from: http://oasys2confexcom/acs/235nm/techprogram/S26267HTM 2008
141. Walters I, Austin C, Austin R, et al. Evaluation of a series of bicyclic CXCR2 antagonists. Bioorg Med Chem Lett 2008;18:798-803
142. Rosenbaum DM, Cherezov V, Hanson MA, et al. GPCR engineering yields high-resolution structural insights into beta2-adrenergic receptor function. Science 2007;318:1266-1273 (Pubitemid 350172885)
143. Rasmussen SG, Choi HJ, Rosenbaum DM, et al. Crystal structure of the human beta2 adrenergic G-protein-coupled receptor. Nature 2007;450:383-387 (Pubitemid 350126755)
144. Schlyer S, Horuk R. I want a new drug: G-protein-coupled receptors in drug development. Drug Discov Today 2006;11:481-493