CXCR2 modulators: A patent review (2009-2013)

Expert Opinion on Therapeutic Patents

Volumn 24, Issue 5, 2014, Pages 519-534

  Dwyer, Michael P ^a   Yu, Younong ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

Chemokine; CXC chemokine receptor 2; CXC chemokine receptor 2 antagonist; Gro (CXCL1); Interleukin 8

Indexed keywords

ALPRENOLOL; CHEMOKINE RECEPTOR CXCR2 ANTAGONIST; ELUBRIXIN; ANTIINFLAMMATORY AGENT; CHEMOKINE RECEPTOR CXCR2;

AUTOINFLAMMATORY DISEASE; DRUG STRUCTURE; HUMAN; INFLAMMATION; LUNG ALVEOLUS MACROPHAGE; NEUTROPHIL CHEMOTAXIS; PUBLICATION; REVIEW; ANIMAL; ANTAGONISTS AND INHIBITORS; DRUG EFFECTS; DRUG INDUSTRY; PATENT;

ANIMALS; ANTI-INFLAMMATORY AGENTS; DRUG INDUSTRY; HUMANS; PATENTS AS TOPIC; RECEPTORS, INTERLEUKIN-8B;

EID: 84898934029     PISSN: 13543776     EISSN: 17447674     Source Type: Journal    
DOI: 10.1517/13543776.2014.887682     Document Type: Review

References (80)

1. Moser B, Dewald B, Barella L, et al. Interleukin-8 antagonists generated by N-terminal modification. J Biol Chem 1993;268(10):7125-8
2. Holmes WE, Lee J, Kuang WJ, et al. Structure and functional expression of a human interleukin-8 receptor. Science 1991;253(5025):1278-80
3. Murphy PM, Tiffany HL. Cloning of complementary DNA encoding a functional human interleukin-8 receptor. Science 1991;253(5025):1280-2
4. Walz A, Burgener R, Carr B, et al. Structure and neutrophil activating properties of a novel inflammatory peptide (ENA-78) with homology to interleukin-8. J Exp Med 1991;174(6):1355-62
5. Wolf M, Delgado MB, Jones SA, et al. Granulocyte chemotactic protein 2 act via both IL-8 receptors, CXCR1 and CXCR2. Eur J Immunol 1998;28(1):164-70
6. Mukaida N. Pathophysiological roles of interleukin-8/CXCL8 in pulmonary diseases. Am J Physiol Lung Cell Mol Physiol 2002;284(10):L566-77
7. Baggiolini M, Dewald B, Moser B. Interleukin-8 and related chemotactic cytokines CXC and CC chemokines. Adv Immunol 1994;55:97-179
8. Luster AD. Chemokines - Chemotactic cytokines that mediate inflammation. N Engl J Med 1998;338(7):436-45
9. Keatings VM, Collins RD, Scott DM. Differences in interleukin-8 and tumor necrosis factor-alpha in induced sputum from patients with chronic obstructive pulmonary disease or asthma. J Am J Respir Crit Care Med 1996;153(2):530-4
10. Donnelly LE, Barnes PJ. Chemokine receptor CXCR2 antagonism to prevent airways inflammation. Drugs Future 2011;36(6):465-72
11. Cacalano G, Lee J, Kikly K, et al. Neutrophil and B cell expansion in mice that lack the murine IL-8 receptor homolog. Science 1994;265(5172):682-4
12. White JR, Lee JM, Young PR, et al. Identification of a potent, selective non-peptide CXCR2 antagonist that inhibits interleukin-8-induced neutrophil migration. J Biol Chem 1998;273(17):10095-8
13. Li JJ. Small molecule interleukin-8 modulators. Expert Opin Ther Patents 2001;11(12):1905-10
14. Gao A, Metz WA. Unraveling the chemistry of chemokine receptor ligands. Chem Rev 2003;103(9):3733-52
15. Busch-Peterson J. Small molecule antagonists of the CXCR2 and CXCR1 chemokine receptors as therapeutic agents for the treatment of inflammatory diseases. Curr Top Med Chem 2006;6(13):1354-62
16. Bizzarri C, Beccari AR, Bertini R, et al. ELR+ CXC chemokines and their receptors (CXC chemokine receptor 1 and CXC chemokine receptor 2) as therapeutic targets. Pharmacol Ther 2006;112(1):139-49
17. Reutershan J. CXCR2 -the receptor to hit? Drug News Perspect 2006;19(10):615-23
18. White JR, Sarau HM. IL-8 receptor antagonist: basic research and clinical utility. Chemokine Biol Basic Res Clin Appl 2007;2:89-102
19. Panina P, Mariani M, DAmbrosio D. Chemokine receptors in chronic obstructive pulmonary disease (COPD). Curr Drug Targets 2006;7(6):669-74
20. Allegretti M, Cesta MC, Garin A, et al. Current status of chemokine receptor inhibitors in development. Immunol Lett 2012;145(1-2):68-78
21. Wijtmans M, Scholten DJ, de Esch IJP, et al. Therapeutic targeting of chemokine receptors by small molecules. Drug Disc Today Tech 2012;9(4):e229-36
22. Chapman RW, Phillips JE, Hipkin RW, et al. CXCR2 antagonists for the treatment of pulmonary disease. Pharmacol Ther 2009;121(1):55-68
23. Virtala R, Ekman AK, Jansson L, et al. Airway inflammation evaluated in a human nasal lipopolysaccharide challenge model by investigating the effect of a CXCR2 inhibitor. Clin Exp Allergy 2011;42(4):590-6
24. Holz O, Khalilieh S, Ludwig-Sengpiel A, et al. SCH 527123, a novel CXCR2 antagonist, inhibits ozone-induced neutrophilia in healthy subjects. Eur Respir J 2010;35(3):564-70
25. Lazaar AL, Sweeney LE, MacDonald AJ, et al. SB-656933, a novel CXCR2 selective antagonist, inhibits ex vivo neutrophil activation and ozone-induced airway inflammation in humans. Br J Clin Pharmacol 2011;72(2):282-93
26. Dwyer MP, Biju P. Discovery of 3,4-diaminocyclobut-3-ene-1,2-dionebased CXCR2 receptor antagonists for the treatment of inflammatory disorders. Curr Top Med Chem 2010;10(13):1339-50
27. Mihara K, Wijkmans J. Low molecular weight CXCR2 antagonists as promising therapeutics. In: Smit MJ, Lira SA, Leurs R, editors, Chemokine receptor as drug targets. Wiley-VCG Verlag GmbH & KgaA, Weiheim, Germany; 2011. p. 279-99
28. Busch-Petersen J, Wang Y. Phenol-containing antagonists of the CXCR2 receptor. Expert Opin Ther Patents 2008;18(6):629-37
29. AstraZeneca AB, AstraZeneca UK Ltd. Preparation of pyrimidine compounds as modulators of chemokine receptor activity. WO2001058902; 2001
30. AstraZeneca AB, AstraZeneca UK Ltd. Preparation of thiazolopyrimidine, pyrazolopyrimidine, triazolopyrimidine, and purine compounds as modulators of chemokine receptor activity. WO2001058906; 2001
31. Anon. Novel pyrimidine-based CXCR2 chemokine receptor antagonists. Expert Opin Ther Patents 2004;14(10):1507-10
32. AstraZeneca AB, AstraZeneca UK Ltd. Pyrimidine sulphonamide derivative and its use for chemokine mediated diseases. WO2010007427; 2010
33. AstraZeneca AB, AstraZeneca UK Ltd. New crystalline forms of N-[2- [[(2,3-difluorophenyl)methyl)thio]- 6-{[(1R,2S)-2,3-dihydroxy-1- methylpropyl]oxy}-4-pyrimindinyl]-1- azetidinesulfonamide. WO2012007748; 2012
34. AstraZeneca AB, AstraZeneca UK Ltd. Pyrimidine sulphonamide derivatives as chemokine receptor modulators. WO2006024823; 2006
35. Norman P. Evidence on the identity of the CXCR2 antagonist AZD-5069. Expert Opin Ther Patents 2013;23(1):113-17
36. AstraZeneca AB, AstraZeneca UK Ltd. N-(6-((2R,3S)-3,4-Dihydroxybutan-2- yloxy)-2-(4-fluorobenzylthio)pyrimidin-4- yl)-3-methylazetidine-1-sulfonamide as chemokine receptor modulators. WO2013008002; 2013
37. Schering-Plough Corp. Methods of treating COPD. WO2009073683; 2009
38. Dwyer MP, Yu Y, Chao J-P, et al. Discovery of 2-hydroxy-N,N-dimethyl-3- {2-[[(R)-1-(5-methylfuran-2-yl)propyl] amino]-3,4-dioxo-cyclobut-1-enylamino} benzamide (SCH 527123): a potent, orally bioavailable CXCR2/ CXCR1 receptor antagonist. J Med Chem 2006;49(26):7603-6
39. Gonsiorek W, Fan X, Hesk D, et al. Pharmacological characterization of Sch 527123, a potent allosteric CXCR1/ CXCR2 antagonist. J Pharm Exp Ther 2007;322(2):477-85
40. Chapman RW, Minnicozzi M, Celly CS, et al. A Novel, orally active CXCR1/ CXCR2 receptor antagonist, Sch527123, inhibits neutrophil recruitment, mucus production, and goblet cell hyperplasia in animal models of pulmonary inflammation. J Pharm Exp Ther 2007;322(2):486-93
41. Chao J-H, Taveras AG, Chao J-P, et al. C(4)-alkyl substituted furanyl cyclobutenediones as potent, orally bioavailable CXCR2 and CXCR1 receptor antagonists. Bioorg Med Chem 2007;17(13):3778-83
42. Nair P, Gaga M, Zervas E, et al. Safety and efficacy of a CXCR2 antagonist in patients with severe asthma and sputum neutrophils: a randomized, placebocontrolled clinical trial. Clin Exp Allergy 2012;42(7):1097-103
43. NCT01006616 Long-Term Extension Study of the Effects of SCH 527123 in Subjects With Moderate to Severe COPD (P05575AM2)(MK-7123-009-0). Available from: http://clinicaltrials.gov/ ct2/show/NCT01006616
44. SmithKline Beecham Corp. Method of treatment. WO2009039091; 2009
45. Moss RB, Mistry SJ, Konstan MW, et al. Safety and early treatment effects of the CXCR2 receptor antagonist SB-656933 in patients with cystic fibrosis. J Cyst Fibros 2013;12(3):241-8
46. NCT01209052 First time in Human Study with GSK1325767. Available from: http://clinicaltrials.gov/ct2/show/ NCT01209052
47. Novartis AG. Heterocyclic compounds as inhibitors of CXCR2. WO2009106539; 2009
48. Baxter A, Cooper A, Kinchin E, et al. Hit-to-lead studies: the discovery of potent, orally bioavailable thiazolopyrimidine CXCR2 receptor antagonists. Bioorg Med Chem 2006;16(4):960-3
49. Novartis Institutes for Biomedical Research, Novartis and Co. Organic compounds. WO2010015613 2010
50. Novartis Institutes for Biomedical Research, Novartis and Co. 3,4-Disubstituted cyclobutene-1,2-diones as CXCR2 receptor antagonists. WO2010063802; 2010
51. Novartis AG. Choline salt of an anti-inflammatory substituted cyclobutenedione compound. WO2013030803; 2013
52. Li JJ, Carson KG, Trivedi BK, et al. Synthesis and structure-activity relationship of 2-amino-3-heteroarylquinoxalines as non-peptide, small molecule antagonists for interleukin-8 receptor. Bioorg Med Chem 2003;11(17):1926
53. Pfizer and Co. Cyclobutenedione derivatives. WO2010131145; 2010
54. Pfizer and Co. Cyclobutenedione derivatives. WO2010131146; 2010
55. Widdowson K, Nie H, Jurewicz AJ, et al. The role of the anionic groups in the receptor binding or interleukin-8 antagonists. Lett Peptide Sci 1998;5:235-9
56. Pfizer and Co. Cyclobutenedione derivatives. WO2010131147; 2010
57. Boehringer-Ingelheim. Bicyclic ring system substituted amide functionalised phenols as medicaments. WO2012080456; 2012
58. Boehringer-Ingelheim. Bicyclic ring system substituted sulfonamide functionalised phenols as medicaments. WO2012080457; 2012
59. Norman P. Evaluation of WO2012080456 and WO2012080457; Boehringer Ingleheims first CXCR2 antagonists. Expert Opin Ther Patents 2013.23(3):383-8
60. Merck and Co. Novel hydrazinocyclobut- 3-ene-1,2-dione derivatives as CXCR2 antagonists. WO2010091543; 2010
61. Liu S, Liu Y, Wang H, et al. Design, synthesis, and evaluation of novel 3-amino-4-hydrazine-cyclobut-3-ene- 1,2-diones as potent and selective CXCR2 chemokine receptor antagonists. Bioorg Med Chem Lett 2009;19(19):5741-5
62. Galderma Research and Development. Novel disubstituted 3,4-diamino-3- cyclobutene-1.2-dione compounds for use in the treatment of chemokinemediated diseases. WO2013061002; 2013
63. Galderma Research and Development. Novel disubstituted 3,4-diamino-3- cyclobutene-1.2-dione compounds for use in the treatment of chemokinemediated diseases. WO2013061004; 2013
64. Galderma Research and Development. Disubstituted 3,4-diamino-3- cyclobutene- 1.2-dione compounds for use in the treatment of chemokine-mediated pathologies. WO2013061005; 2013
65. Syntrix Biosystems Corp. Pyridine- and pyrimidine carboxamides as CXCR2 modulators. US20100210593; 2010
66. Syntrix Biosystems Corp. Aminopyridine- and Aminopyrimidine carboxamides as CXCR2 modulators. US20120046243; 2012
67. Bertini R, Allegretti M, Bizzarri C, et al. Non-competitive allosteric inhibitors of the inflammatory chemokine receptors CXCR1 and CXCR2: prevention of reperfusion injury. Proc Natl Acad Sci USA 2004;101(32):11791-6
68. Dompé s.p.a. 2-Aryl-propionic acids and derivatives and pharmaceutical compositions containing them. WO2010031835; 2010
69. Dompé s.p.a. Inhibitors of CXCR1/2 as Adjuvants in the transplant of pancreatic Islets. WO2011042466
70. Moriconi A, Bigogno C, Bianchini G, et al. Aryltriflates as a neglected moiety in medicinal chemistry: a case study from a lead optimization of CXCL8 inhibitors. ACS Med Chem Lett 2011;2(10):768-73
71. NCT01220856 Reparixin in pancreatic islet transplantation. Available from: http://clinicaltrials.gov/ct2/show/ NCT01220856
72. Kaur M, Singh D. Neutrophil chemotaxis caused by chronic obstructive pulmonary disease alveolar macrophages: the role of CXCL8 and the receptors CXCR1/CXCR2. J Pharmacol Exp Ther 2013;347(1):173-80
73. Aul R, Patel S, Summerhill S, et al. LPS challenge in healthy subjects: an investigation of neutrophil chemotaxis mechanisms involving CXCR1 and CXCR2. Int Immunopharmacol 2012;13(3):225-31
74. Bertini R, Barcelos LS, Beccari AR, et al. Receptor binding mode and pharmacological characterization of a potent and selective dual CXCR1/ CXCR2 non-competitive allosteric inhibitor. Br J Pharm 2012;165(2):436-54
75. Seiberling M, Kamtchoua T, Strysak P, et al. Humoral immunity and delayed hypersensitivity in healthy subjects treated for 30 days with MK-7123, a selective CXCR2 antagonist. Int Immunopharmacol 2013;17(2):178-83
76. Singh RK, Varney ML. IL-8-expression in malignant melanoma: implications in growth and metastasis. Histol Histopathol 2000;15(3):843-9
77. Hertzer KM, Donald GW, Hines OJ. CXCR2: a target for pancreatic cancer treatment? Expert Opin Ther Targets 2013;17(6):667-80
78. Singh S, Sadanandam A, Nannuru KC. Small-molecule antagonists for CXCR2 and CXCR1 inhibit human melanoma growth by decreasing tumor cell proliferation, survival, and angiogenesis. Clin Cancer Res 2009;15(7):2380-6
79. Varney ML, Singh S, Li A, et al. Small molecule antagonists for CXCR2 and CXCR1 inhibit human colon cancer liver metastases. Cancer Lett 2011;300(2):180-8
80. Ning Y, Labonte MJ, Zhang W, et al. The CXCR2 antagonist, SCH 527123, shows antitumor activity and sensitizes cells to oxaliplatin in preclinical colon cancer models. Mol Cancer Ther 2012;11(6):1353-64