Current status of leukotriene A4 hydrolase inhibitors

Expert Opinion on Therapeutic Patents

Volumn 18, Issue 12, 2008, Pages 1333-1350

  Grice, Cheryl A ^a   Gomez, Laurent ^a  

^a JOHNSON AND JOHNSON PHARMACEUTICAL RESEARCH AND DEVELOPMENT   (United States)

Author keywords

Arachidonic acid; Eicosanoid; Immune mediated inflammatory disease; Inflammation; Leukotriene A4 hydrolase; Leukotriene B4 synthesis inhibitor

Indexed keywords

BESTATIN; CYCLOOXYGENASE 2 INHIBITOR; DG 051; ENZYME INHIBITOR; HYDROLASE INHIBITOR; KELATORPHAN; LEUKOTRIENE A4; LEUKOTRIENE A4 HYDROLASE; LEUKOTRIENE A4 HYDROLASE INHIBITOR; LEUKOTRIENE B4; MONTELUKAST; PLACEBO; SA 6541; SC 22716; SC 56938; SC 57461; SC 57461A; UNCLASSIFIED DRUG;

ARTHRITIS; ASTHMA; AUTOIMMUNE DISEASE; CLINICAL TRIAL; DRUG EFFICACY; DRUG STRUCTURE; DRUG TARGETING; ENZYME ACTIVITY; ENZYME INHIBITION; ENZYME LOCALIZATION; GRAFT REJECTION; HEART INFARCTION; HUMAN; IC 50; INFLAMMATORY DISEASE; NONHUMAN; PATENT; PSORIASIS; REVIEW; ULCERATIVE COLITIS;

EID: 57749120365     PISSN: 13543776     EISSN: None     Source Type: Journal    
DOI: 10.1517/13543770802494100     Document Type: Review

References (107)

1. Kim N, Luster AD. Regulation of immune ceiis by eicosanoid receptors. Sci World J 2007;7:1307-28
2. Rubin P, Mollison KW. Pharmacotherapy of diseases mediated by 5-lipoxygenase pathway eicosanoids. Prostaglandins Other Lipid Mediat 2007;83(3):188-97
3. Peters-Golden M, Henderson WR Jr. Leukotrienes. N Engl J Med 2007;357(18)1841-54
4. Borgeat P, Hamberg M, Samuelsson B. Transformation of arachidonic acid and homo-gamma-linolenic acid by rabbit polymorphonuclear leukocytes. Monohydroxy acids from novel lipoxygenases. J Biol Chem 1976;251(24)7816-20
5. Brocklehurst WE. Slow reacting substance and related compounds. Prog Allergy 1962;6:539-58
6. Borgeat P, Sirois P. Leukotrienes: a major step in the understanding of immediate hypersensitivity reactions. J Med Chem 1981;24(2):121-6
7. Haeggstrom JZ. Leukotriene A4 hydrolase/aminopeptidase, the gatekeeper of chemotactic leukotriene B4 biosynthesis. J Biol Chem 2004;279(49):50639-42
8. Haeggstrom JZ, Kull F, Rudberg PC, et al. Leukotriene A4 hydrolase. Prostaglandins Other Lipid Mediat 2002;68-69:495-510
9. Del Prete A, Shao W-H, Mitola S, et al. Regulation of dendritic cell migration and adaptive immune response by leukotriene B4 receptors: a role for LTB4 in up-regulation of CCR7 expression and function. Blood 2007;109(2):626-31
10. Goetzl EJ, Goldman DW, Naccache PH, et al. Mediation of leukocyte components of inflammatory reactions by lipoxygenase products of arachidonic acid. Adv Prostaglandin Thromboxane Leukot Res 1982;9:273-82
11. Goodarzi K, Goodarzi M,Tager AM, et al. Leukotriene B4 and BLT1 control cytotoxic effector T cell recruitment to inflamed tissues. Nat Immunol 2003;4(10):965-73
12. Heller EA, Liu E, Tager AM, et al. Inhibition of atherogenesis in BLT1-deficient mice reveals a role for LTB4 and BLT1 in smooth muscle cell recruitment. Circulation 2005;112(4):578-86
13. Iizuka Y, Yokomizo T, Terawaki K, et al. Characterization of a mouse second leukotriene B4 receptor, mBLT2: BLT2-dependent ERK activation and cell migration of primary mouse keratinocytes. J Biol Chem 2005;280(26):24816-23
14. Lundeen KA, Sun B, Karlsson L, Fourie AM. Leukotriene B4 receptors BLT1 and BLT2: expression and function in human and murine mast cells. J Immunol 2006;177(5):3439-47
15. Munoz NM, Douglas I, Mayer D, et al. Eosinophil chemotaxis inhibited by 5-lipoxygenase blockade and leukotriene receptor antagonism. Am J Respir Crit Care Med 1997;155(4):1398-403
16. Ott VL, Cambier JC, Kappler J, et al. Mast cell-dependent migration of effector CD8+ T cells through production of leukotriene B4. Nat Immunol 2003;4(10):974-81
17. Tager AM, Bromley SK, Medoff BD, et al. Leukotriene B4 receptor BLT1 mediates early effector T cell recruitment. Nat Immunol 2003;4(10):982-90
18. Rask-Madsen J. Soluble mediators and the interaction of drugs in IBD. Drugs Today Barc 1998;34(1):45-63
19. Sharon P, Stenson WF. Enhanced synthesis of leukotriene B4 by colonic mucosa in inflammatory bowel disease. Gastroenterology 1984;86(3):453-60
20. Griffiths RJ, Pettipher ER, Koch K, et al. Leukotriene B4 plays a critical role in the progression of collagen-induced arthritis. Proc Natl Acad Sci USA 1995;92(2):517-21
21. Shao WH, Del Prete A, Bock CB, Haribabu B. Targeted disruption of leukotriene B4 receptors BLT1 and BLT2: a critical role for BLT1 in collagen-induced arthritis in mice. J Immunol 2006;176(10):6254-61
22. Tsuji F, Oki K, Fujisawa K, et al. Involvement of leukotriene B4 in arthritis models. Life Sci 1999;64(3):PL51-6
23. Barnes PJ. New treatments fist COPD. Nat Rev Drug Discov 2002;1(6):437-46
24. Gompertz S, Stockley RA. A randomized, placebo-controlled trial of a leukotriene synthesis inhibitor in patients with COPD. Chest 2002;122(1):289-94
25. Lemiere C, Pelissier S, Tremblay C, et al. Leukotrienes and isocyanate-induced asthma: a pilot study. Clin Exp Allergy 2004;34(11):1684-9
26. Luster AD, Tager AM. T-cell trafficking in asthma: lipid mediators grease the way. Nat Rev Immunol 2004;4(9):711-24
27. Terawaki K, Yokomizo T, Nagase T, et al. Absence of leukotriene B4 receptor 1 confers resistance to airway hyperresponsiveness and Th2-type immune responses. J Immunol 2005;175(7):4217-25
28. Montuschi P, Sala A, Dahlen SE, Folco G. Pharmacological modulation of the leukotriene pathway in allergic airway disease. Drug Discov Today 2007;12(9-10):404-12
29. Chen X, Wang S, Wu N, Yang CS. Leukotriene A4 hydrolaae as a target for cancer prevention and therapy. Curr Cancer Drug Targets 2004;4(3):267-83
30. Back M, Bu DX, Branstrom R, et al. Leukotriene B4 signaling through NF-kappaB-dependent BLT1 receptors on vascular smooth muscle cells in atherosclerosis and intimal hyperplasia. Proc Natl Acad Sci USA 2005;102(48):17501-6
31. Back M, Hansson GK. Leukotriene receptors in atherosclerosis. Ann Med 2006;38(7):493-502
32. Friedrich EB, Tager AM, Liu E, et al. Mechanisms of leukotriene B4-triggered monocyte adhesion. Arterioscler Thromb Vasc Biol 2003;23(10):1761-7
33. Funk CD. Leukotriene modifiers as potential therapeutics for cardiovascular disease. Nat Rev Drug Discov 2005;4(8):664-72
34. Helgadottir A, Gretarsdottir S, St Clair D, et al. Association between the gene encoding 5-lipoxygenase-activating protein and stroke replicated in a Scottish population. Am J Hum Genet 2005;76(3):505-9
35. Helgadottir A, Manolescu A, Helgason A, et al. A variant of the gene encoding leukotriene A4 hydrolase confers ethnicity-specific risk of myocardial infarction. Nat Genet 2006;38(1):68-74
36. Helgadottir A, Manolescu A, Thorleifsson G, et al. The gene encoding 5-lipoxygenase activating protein confers risk of myocardial infarction and stroke. Nat Genet 2004;36(3):233-9
37. Jala VR, Haribabu B. Leukotrienes and atherosclerosis: new roles for old mediators. Trends Immunol 2004;25(6):315-22
38. Qiu H, Gabrielsen A, Agardh HE, et al. Expression of 5-lipoxygenase and leukotriene A4 hydrolase in human atherosclerotic lesions correlates with symptoms of plaque instability. Proc Natl Acad Sci USA 2006;103(21):8161-6
39. Subbarao K, Jala VR, Mathis S, et al. Role of leukotriene B4 receptors in the development of atherosclerosis: potential mechanisms. Arterioscler Thromb Vasc Biol 2004;24(2):369-75
40. Whatling C, McPheat W, Herslof M. The potential link between atherosclerosis and the 5-lipoxygenase pathway: investigational agents with new implications for the cardiovascular field. Expert Opin Investig Drugs 2007;16(12):1879-93
41. Byrum RS, Goulet JL, Snouwaert JN, et al. Determination of the contribution of cysteinyl leukotrienes and leukotriene B4 in acute inflammatory responses using 5-lipoxygenase- and leukotriene A4 hydrolase-deficient mice. J Immunol 1999;163(12):6810-9
42. Chen M, Lam BK, Kanaoka Y, et al. Neutrophil-derived leukotriene B4 is required for inflammatory arthritis. J Exp Med 2006;203(4):837-42
43. Brooks CD, Summers JB. Modulators of leukotriene biosynthesis and receptor activation. J Med Chem 1996;39(14):2629-54
44. Evans JF, Ferguson AD, Mosley RT, Hutchinson JH. What's all the FLAP about: 5-lipoxygenase-activating protein inhibitors for inflammatory diseases. Trends Pharmacol Sci 2008;29(2):72-8
45. Peters-Golden M, Brock TG. 5-lipoxygenase and FLAP Prostaglandins Leukot Essent Fatty Acids 2003;69(2-3):99-109
46. Vickers PJ. 5-Lipoxygenase-activating protein (FLAP). J Lipid Mediat Cell Signal 1995;12(2-3):185-94
47. Hicks A, Monkarsh SP, Hoffman AF, Goodnow R Jr. Leukotriene B4 receptor antagonists as therapeutics for inflammatory disease: preclinical and clinical developments. Expert Opin Investig Drugs 2007;16(12):1909-20
48. Yokomizo T, Kato K, Terawaki K, et al. A second leukotriene B4; receptor, BLT2. A new therapeutic target in inflammation and immunological disorders. J Exp Med 2000;192(3):421-32
49. Kamohara M, Takasaki J, Matsumoto M, et al. Molecular cloning and characterization of another leukotriene B4 receptor. J Biol Chem 2000;275(35):27000-4
50. Tryselius Y, Nilsson NE, Kotarsky K, et al. Cloning and characterization of cDNA encoding a novel human leukotriene B4; receptor. Biochem Biophys Res Commun 2000;274(2):377-82
51. Wang S, Gustafson E, Pang L, et al. A novel hepatointestinal leukotriene B4 receptor. Cloning and functional characterization. J Biol Chem 2000;275(52):40686-94
52. Yokomizo T, Izumi T, Chang K, et al. A G-protein-coupled receptor for leukotriene B4 that mediates chemotaxis. Nature 1997;387(6633):620-4
53. Serhan CN, Hamberg M, Samuelsson B. Lipoxins: novel series of biologically active compounds formed from arachidonic acid in human leukocytes. Proc Natl Acad Sci USA 1984;81(17):5335-9
54. Serhan CN. Resolution Phase of Inflammation: Novel Endogenous Anti-Inflammatory and Proresolving Lipid Mediators and Pathways. Annu Rev Immunol 2007;25(1):101-37
55. Rao NL, Dunford PJ, Xue X, et al. Anti-inflammatory activity of a potent, selective leukotriene A4 hydrolase inhibitor in comparison with the 5-lipoxygenase inhibitor zileuton. J Pharmacol Exp Ther 2007;321(3):1154-60
56. Penning TD, Chandrakumar NS, Chen RB, et al. Structure-activity relationship studies on 1-[2-(4-Phenylphenoxy)ethyl] pyrrolidine (SC-22716), a potent inhibitor of leukotriene A4; (LTA4;) hydrolase. J Med Chem 2000;43(4):721-35
57. Penning TD, Russell MA, Chen BB, et al. Synthesis of potent leukotriene A4; hydrolase inhibitors. Identification of 3-[methyl[3-[4-(phenylmethyl)phenoxy] propyl]amino]propanoic acid. J Med Chem 2002;45(16):3482-90
58. Thunnissen MM, Nordlund P, Haeggstrom JZ. Crystal structure of human leukotriene A4; hydrolase, a bifunctional enzyme in inflammation. Nat Struct Biol 2001;8(2):131-5
59. Thunnissen MM, Andersson B, Samuelsson B, et al. Crystal structures of leukotriene A4 hydrolase in complex with captopril and two competitive tight-binding inhibitors. Faseb J 2002;16(12):1648-50
60. Penning TD. Inhibitors of leukotriene A4 (LTA4) hydrolase as potential anti-inflammatory agents. Curr Pharm Des 2001;7(3):163-79
61. Friesen RW, Riendeau D. Leukotriene Biosynthesis Inhibitors. Annual Reports in Medicinal Chemistry: Academic Press. 2005:199-214
62. Orning L, Krivi G, Fitzpatrick FA. Leukotriene A4 hydrolase. Inhibition by bestatin and intrinsic aminopeptidase activity establish its functional resemblance to metallohydrolase enzymes. J Biol Chem 1991;266(3):1375-8
63. Penning TD, Askonas LJ, Djuric SW, et al. Kelatorphan and related analogs: potent and selective inhibitors of leukotriene A4 hydrolase. Bioorg Med Chem Lett 1995;5(21):2517-22
64. Tsuji F, Miyake Y, Enomoto H, et al. Effects of SA6541, a leukotriene A4 hydrolase inhibitor, and indomethacin on carrageenan-induced murine dermatitis. Eur J Pharmacol 1998;346(1):81-5
65. British Biotech Pharmaceuticals Limited: WO199940910; 1999
66. Novel leukotriene A4 hydrolase inhibitors. Expert Opin Ther Patents 1999;9(1):91-5
67. G.D.Searle & Co.: WO199611192; 1996
68. G.D.Searle & Co.: WO199610999; 1996
69. G.D. Searle & Co.: US5,585,492; 1996
70. G.D. Searle & Co.: US5,719,306; 1998
71. G.D. Searle & Co.: US5,723492; 1998
72. G.D. Searle & Co.: US6,506,876; 2003
73. Penning TD, Chandrakumar NS, Desai BN, et al. Pyrrolidine and piperidine analogues of SC-57461A as potent, orally active inhibitors of leukotriene A4; hydrolase. Bioorg Med Chem Lett 2002;12(23):3383-6
74. G.D. Searle & Co.: WO199644625; 1996
75. G.D. Searle & Co.: WO199729774; 1997
76. G.D. Searle & Co.: US5,990,148; 1999
77. G.D. Searle & Co.: US5,700,816; 1997
78. G.D. Searle & Co.: US6407140B1; 2002
79. G.D. Searle & Co.: WO199840354; 1998
80. G.D. Searle & Co.: US6,162,823; 2000
81. G.D. Searle & Co.: WO199840364; 1998
82. G.D. Searle & Co.: US5,925,654; 1999
83. G.D. Searle & Co.: US6,265,433B1; 2001
84. G.D. Searle & Co.: WO199840370; 1998
85. G.D. Searle & Co.: US 6,110,944; 2000
86. Janssen Pharmaceutica N.V.: WO2005012297; 2005
87. Janssen Pharmaceutica N.V.: WO2005012296; 2005
88. Janssen Pharmaceutica N.V.: WO2006105304; 2006
89. These applications are assigned to either deCODE Chemistry, Inc. or deCODE genetics ehf
90. deCODE Chemistry, Inc.: US20070066820; 2007
91. Sandanayaka V, Mamat B, Yu P, et al. DG-051: A novel leukottiene A4 hydrolase inhibitor for the treatment of myocardial infarction and stroke. The 233rd ACS National Meeting, 2007 March 25-29; Chicago: IL, USA
92. deCODE Announces Positive Topline Results for Phase I Study of DG051 for the Prevention of Heart Attack. Available from: http://wwwdecode.com/ News/2007_05_01.php
93. deCODE Launches Phase II Clinical Testing of DG051 for the Prevention of Heart Attack. Available from: http:www.decode.com/News/2007_10_09.php
94. Sandanayaka V, Mamat B, Bedell L, et al. Design, synthesis, and SAR of novel leukotriene A4 hydrolase inhibitors containing chiral piperidine and piperazine scaffolds. 232nd ACS National Meeting, 2006 September 10-14; San Francisco: CA, USA
95. Zhao L, Mamat B, Mishra R, et al. Discovery of indazole derivatives as potent leukotriene A4 hydrolase inhibitors. 232nd ACS National Meeting, 2006 September 10-14; San Francisco: CA, USA
96. deCODE Chemistry, Inc.: WO2007073407; 2007
97. deCODE Chemistry, Inc.: US20070142432; 2007
98. deCODE Chemistry, Inc.: WO2007073405; 2007
99. deCODE Chemistry, Inc.: US20070142434; 2007
100. deCODE genetics, ehf.: US20080033013; 2008
101. deCODE Chemistry, Inc.: US20070149544; 2007
102. deCODE genetics, ehf.: US20080033024; 2008
103. deCODE genetics, ehf.: US2008019284; 2008
104. Schering AG: US20070155726; 2007
105. Schering AG: WO2007079003; 2007
106. Schering AG: US20070155727; 2007
107. deCODE genetics Announces First Quarter 2008 Financial Results. Available from: http://www.decode.com/News/2008_05_01.php