Advertisement

Lipoxygenase Inhibitors and Leukotriene Receptor Antagonists

  • B. J. Fitzsimmons
  • J. Rokach
Part of the Advances in Eicosanoid Research book series (AEIR, volume 3)

Abstract

The object of this chapter is to give the reader an overview of the numerous agents that directly modulate the effects of the leukotriene section of the arachidonic acid cascade (Figure 8.1). These agents fall into two general categories: enzyme inhibitors and receptor antagonists. Compounds in the former category exercise their effect by reducing or preventing the formation of the biologically active products of this pathway, while those in the latter group do so by competitively occupying the receptor through which a specific leukotriene manifests its action.

Keywords

Caffeic Acid Butylate Hydroxy Toluene Arachidonic Acid Cascade Caffeic Acid Derivative LTA4 Hydrolase 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Corey, E.J., Clark, D.A., Goto, G., Marfat, A., Mioskowski, C., Samuelsson, B. and Hammarström, S. (1980). Stereospecific total synthesis of a ‘slow reacting substance’ of anaphylaxis, leukotriene C-1. J. Am. Chem. Soc., 102, 1436–9 and p3663Google Scholar
  2. 2.
    Morris, H.R., Taylor, G.W., Rokach, J., Girard, Y., Piper, P.J., Tippins, J.R. and Samhoun, M.N. (1980). Slow reacting substance of anaphylaxis, SRS-A: assignment of the stereochemistry. Prostaglandins,20, 601–607PubMedGoogle Scholar
  3. 3.
    Samuelsson, B. (1983). Leukotrienes: a new class of mediators of immediate hypersensitivity reactions and inflammation. In Samuelsson, B., Ramwell, P.W. and Paoletti, R. (eds.) Advances in Prostaglandin, Thromboxane and Leukotriene Research, Vol. 11, pp. 1–13Google Scholar
  4. 4.
    Ford-Hutchinson, A.W. (1983). The role of leukotriene B4 as a mediator of leukocyte function. Agents Action, 12 (Suppl.), 154–165Google Scholar
  5. 5.
    Mong, S., Wu, H.L., Scott, M.O., Lewis, M.A., Clark, M.A., Weichman, B.M., Kinzig, C.M., Gleason, J.G. and Crooke, S.T. (1985). Molecular heterogeneity of leukotriene receptors: correlation of smooth muscle contraction and radioligand binding in guinea pig lung. J. Pharmacol. Exp. Ther., 234, 316–325PubMedGoogle Scholar
  6. 6.
    Goldman, D.W. and Goetzl, E.J. (1984). Heterogeneity of human polymorphonuclear leukocyte receptors for leukotriene B4. Identification of a subset of high affinity receptors that transduce the chemotactic response. J. Exp. Med., 159, 1027–1041PubMedGoogle Scholar
  7. 7.
    Rouzer, C.A. and Samuelsson, B. (1985). On the nature of the 5-lipoxygenase reaction in human leukocytes: Enzyme purification and requirement for multiple stimulatory factors. Proc. Natl. Acad. Sci. USA,82, 6040–6044PubMedGoogle Scholar
  8. 8.
    Dahinden, C.A., Clancy, R.M., Gross, M., Chiller, J.M. and Hugli, T.E. (1985). Leukotriene C4 production by murine mast cells: Evidence for a role for extracellular leukotriene A4. Proc. Natl. Acad. Sci. USA, 82, 6632–6636PubMedGoogle Scholar
  9. 9.
    McGee, J. and Fitzpatrick, F. (1985). Enzymic hydration of leukotriene A,. Purification and characterization of a novel epoxide hydrolase from human erythrocytes. J. Biol. Chem., 260, 12832–12837PubMedGoogle Scholar
  10. 10.
    Pong, S.S., Dehaven, R.N., Kuehl, F.A. Jr. and Egan, R.W. (1983). Leukotriene C4 binding to rat lung membranes. J. Biol. Chem.,258, 9616–9619PubMedGoogle Scholar
  11. 11.
    Yoshimoto, T., Furukawa, M., Yamamoto, S., Horie, T. and Watanabe-Kohno, S. (1983). Flavonoids: potent inhibitors of arachidonate 5-lipoxygenase. Biochem. Biophys. Res. Commun.,116, 612–618PubMedGoogle Scholar
  12. 12.
    Yamamoto, S., Yoshimoto, T., Furukawa, M., Horie, T. and Watanabe-Kohno, S. (1984). Arachidonate 5-lipoxygenase and its new inhibitors. J. Allergy Clin. Immunol., 74, 349–352PubMedGoogle Scholar
  13. 13.
    Panossian, A.G. (1984). Inhibition of arachidonic acid 5-lipoxygenase of human polymorphonuclear leukocytes by esculetin. Biomed. Biochim. Acta,43, 1351–1355PubMedGoogle Scholar
  14. 14.
    Neichi, T., Koshihara, Y. and Murota, S. (1983). Inhibitory effect of esculetin on 5lipoxygenase and leukotriene biosynthesis. Biochim. Biophys. Acta, 753, 130–132PubMedGoogle Scholar
  15. 15.
    Sekiya, K., Okuda, H. and Arichi, S. (1982). Selective inhibition of platelet lipoxygenase by esculetin. Biochim. Biophys. Ada, 713, 68–72Google Scholar
  16. 16.
    Koshihara, Y., Neichi, T., Murota, S., Lao, A., Fujimoto, Y. and Tatsuno, T. (1984). Caffeic acid is a selective inhibitor for leukotriene biosynthesis. Biochim. Biophys. Acta, 792, 92–97PubMedGoogle Scholar
  17. 17.
    Otsuka Pharmaceutical Co. Ltd. (1984). Flavone derivatives. Jpn. Pat. S 60–100, 570, (1985) Chem.. Abstr., 103, 178100rGoogle Scholar
  18. 18.
    Otsuka Pharmaceutical Co. Ltd. (1985). Flavone derivative preparation as inhibitors of arachidonic acid 5-lipoxygenase for the treatment of asthma. Jpn. Pat. S 60–25,923, (1985) Chem. Abstr., 103, 59301Google Scholar
  19. 19.
    Wakabayashi, T., Takai, M., Ichikawa, S., Arai, J. and Murota, S. (1986). Amide derivatives and 5-lipoxygenase inhibitors containing them as active ingredients. Jpn. Pat. S61, 22057 (1986). EP 157420A2 Chem. Abstr., 104, 168177CGoogle Scholar
  20. 20.
    Watanabe, M., Sugiura, M., Fukaya, C., Kondo T. and Yokoyama, K. (1984). Selective inhibition of 5-lipoxygenase by caffeic acid derivatives. Abstract. p. 178. Presented at the Kyoto Conference on Prostaglandins,November 26–28, Kyoto, JapanGoogle Scholar
  21. 21.
    Yokoyama, K., Fukaya, C., Sugiura, M., Naito, Y. and Suyama, T. (1985). Lipoxygenase inhibitor. Eur. Pat. Appl. EP 85106390 (1985) Google Scholar
  22. 22.
    Reddana, P., Rao, M.K. and Reddy, C.C. (1985). Inhibition of 5-lipoxygenase by vitamin E. FEBS Lett.,193, 39–43Google Scholar
  23. 23.
    Moore, G.G.I. and Swingle, K.F. (1982). 2,6-Di-tert-butyl-4-(2’-thenoyl)phenol(R-830): a novel nonsteroidal anti-inflammatory agent with antioxidant properties. Agents Actions, 12, 674–683PubMedGoogle Scholar
  24. 24.
    Hidaka, T., Hosoe, K., Ariki, Y., Takeo, K., Yamashita, T., Katsumi, I., Kondo, H., Yamashita, K. and Watanabe, K. (1984). Pharmacological properties of a new anti-inflammatory compound, α-(3,5-di-tert-butyl-4-hydroxybenzylidene)-γ-butyrolactone (KME-4), and its inhibitory effects on prostaglandin synthetase and 5-lipoxygenase. Jpn. J. Pharmacol.,36, 77–85PubMedGoogle Scholar
  25. 25.
    Hidaka, T., Takeo, K., Hosoe, K., Katsumi, I., Yamashita, T. and Watanabe, K. (1985). Inhibition of polymorphonuclear leukocyte 5-lipoxygenase and platelet cyclooxygenase by a-(3,5-di-tert-butyl-4-hydroxybenzylidene)-7-butyrolactone (KME-4), a new anti-inflammatory drug. Jpn. J. Pharmacol., 38, 267–272PubMedGoogle Scholar
  26. 26.
    Hope, W.C., Welton, A.F., Nagy, C.F. and Coffey, J.W. (1981). Quercetin inhibits SRS-A biosynthesis and lipoxygenase activity in vitro. Fed. Proc.,40 (Abstr.), 4488Google Scholar
  27. 27.
    Murase, K., Arima, H., Mase, T. and Tomioka, K. (1985). Catechol derivatives. Eur. Pat. 0125919. Chem. Abstr., 102, 113041gGoogle Scholar
  28. 28.
    Miyamoto, T. and Obata, T. (1983). New inhibitors of 5-lipoxygenase. Int. Congr. 5er. Excerpta Med., 623, 78–80Google Scholar
  29. 29.
    Arai, Y., Wakatsuka, H., Mohri, T., Obata, T. and Miyamoto, T. (1985). Aminophenol derivative: a potent inhibitor for 5-lipoxygenase. In Hayaishi, O. and Yamamoto, S. (eds.) Advances in Prostaglandin, Thromboxane and Leukotriene Research. Vol. 15, p. 313. (New York: Raven Press)Google Scholar
  30. 30.
    Miyamoto, T., Mohn, T., Shimoi, K., Wakatsuka, H., Itoh, H., Hayashi, M. and Hashimoto, S. (1983). 2-Aminophenol derivatives. Eur. Pat. EP 81321 A (1983), Chem. Abstr.,99, 104990HGoogle Scholar
  31. 31.
    Miyamoto, T., Watsuka, H., Hashimoto, S., Itoh, H., Mohri, T., Hayashi, M. (1983). Aminoresorcinol derivatives. Eur. Pat. EP 79141 (1983), Chem. Abstr., 99, 121998jGoogle Scholar
  32. 32.
    Aharony, D., Smith, J.B. and Silver, M.J. (1981). Inhibition of platelet lipoxygenase by toluene-3,4-dithiol and other ferric iron chelators. Prostagl. Med., 6, 237–242Google Scholar
  33. 33.
    Peterson, D.A. and Gerrard, J.M. (1983). Inhibition of platelet lipoxygenase by toluene3,4-dithiol and other ferric iron chelators. Prostagl. Leuk. Med., 10, 107–108Google Scholar
  34. 34.
    Karanewsky, D.S. and Haslanger, M.F. (1986). Arylydroxamates. Eur. Pat. EP 161939A2 (1986), Chem. Abstr., 104, 148549xGoogle Scholar
  35. 35.
    Veb Arzneimittelwerk Dresden (1985). ω-(2-Naphythoxy) alkylhydroxamic acids. Jpn. Pat. JP 59/205345 (1984), Chem. Abstr.,102, 166495gGoogle Scholar
  36. 36.
    Summers, J.B., Holms, J.H., Ayer, R.D., Carter, G.W. and Summers, J.B., Mazdiyasni, H., Ratazezyk, J.D., Dyer, R.D. and Carter, G.W. (1986). Hydroxamic acid inhibitors of 5lipoxygenase I: structure activity relationships in simple hydroxamic acids. Abstracts MEDI19,20. Presented at The American Chemical Soc. Natl. Meeting. September 7–12, Anaheim, CaliforniaGoogle Scholar
  37. 37.
    Strasser, M. (1985). N-(naphthylalkyl)hydroxylamines. Eur. Pat. Appl. EP 149, 588 (1984), Chem, Abstr., 103, 215016rGoogle Scholar
  38. 38.
    Yoshimoto, T., Yokoyama, C., Ochi, K., Yamamoto, S., Maki, Y., Ashida, Y., Terao, S. and Shiraishi, M. (1982). 2,3,5-Trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinone (AA861), a selective inhibitor of the 5-lipoxygenase reaction and the biosynthesis of slow-reacting substance of anaphylaxis. Biochim. Biophys. Acta, 713, 470–473PubMedGoogle Scholar
  39. 39.
    Ashida, Y., Saijo, T., Kuriki, H., Makino, H., Terao, S. and Maki, Y. (1983). Pharmacological profile of AA-861, a 5-lipoxygenase inhibitor. Prostaglandins,26, 955–972PubMedGoogle Scholar
  40. 40.
    Ishihara, Y., Kitamura, S. and Takaku, F. (1983). Effect of lipoxygenase inhibitors, AA-861 and T-22083, on chemical mediators released from sensitized guinea pig lung tissue. Prostaglandins,26, 623–629PubMedGoogle Scholar
  41. 41.
    Ishihara, Y., Uchida, Y., Kitamura, S. and Takaku, F. (1985). Effect of coenzyme Q10, a quinone derivative, on guinea pig lung and tracheal tissue. Arzneim-Forsch.,35, 929–933Google Scholar
  42. 42.
    Fleisch, J.H., Haisch, K.D., Spaethe, S.M., Rinkema, L.E., Cullinan, C.J., Schmidt, M.J. and Marshall, W.S. (1984). Pharmacologic analysis of two novel inhibitors of leukotriene (slow reacting substance) release. J. Pharmacol. Exp. Ther., 229, 681–689PubMedGoogle Scholar
  43. 43.
    Murthy, D.V.K., Kruseman-Aretz, M., Rouhafza-Fard, S., Bedord, C.J., Young, J.M., Jones, G. and Venuti, M. (1985). Selective inhibition of arachidonic acid (AA) 5-lipoxygenase by a novel anti-psoriatic agent. Fed. Proc., 44, 886 (Abstr. 2774)Google Scholar
  44. 44.
    Iwaki, H., Fukuyama, Y. and Matsui, K. (1986). 1,4-Benzoquinone derivatives and benzene derivatives. Eur. Pat, Appl. EP 151, 995 (1985), Chem. Abstr.,104, 33861qGoogle Scholar
  45. 45.
    Otsuka Pharmaceutical Co. Ltd. Predominantly Z-substituted allylic alcohols and their uses. Jpn. Pat. JP 56–075442A Google Scholar
  46. 46.
    Guindon, Y., Girard, Y., Maycock, A., Ford-Hutchinson, A.W., Atkinson, J.G., Bélanger, P.C., Dallob, A., DeSousa, D., Dougherty, H., Egan, R., Ham, E., Fortin, R., Hamel, P., Hamel, R., Lau, C.K., Leblanc, Y., McFarlane, C.S., Piechuta, H., Thérien, M., Yoakim, C. and Rokach, J. (1987). L-651,392, a novel, potent and selective 5-lipoxygenase inhibitor. In Samuelsson, B., Paoletti, R. and Ramwell, P.W. (eds.) Advances in Prostaglandin, Thromboxane and Leukotriene Research. Vol. 17A, pp. 554–557. (New York: Raven Press)Google Scholar
  47. 47.
    Guindon, Y., Fortin, R., Lau, C.K., Rokach, J. and Yoakim, C. (1984). Phenothiazene derivatives and analogs. Eur. Pat. Appl. EP 115, 394 (1984, Chem. Abstr., 101,230555tGoogle Scholar
  48. 48.
    Bailey, D.M. (1985). Substituted aminobenzamides and their use as agents which inhibit lipoxygenase activity. U.S. Pat. US 4, 510,139 (1985), Chem. Abstr., 103, 71072fGoogle Scholar
  49. 49.
    Bailey, D.M. (1985). Substituted aminobenzoates and their use. U.S. Pat, US 4, 515, 980 (1985), Chem. Abstr., 103, 123174nGoogle Scholar
  50. 50.
    Lin, C.H. (1985). Pyridinylmethylamino-arylic acids. Eur. Pat. Appl. EP 114, 734 (1984), Chem. Abstr., 102, 62086rGoogle Scholar
  51. 51.
    Bonney, R.J., Hand, K., Opas, E.E., Olson, B., Dallob, A., Argenbright, L. and Humes, J.L. (1986). L-651,896 A novel dual inhibitor of prostaglandin and leukotriene synthesis that possesses potent topical antiinflammtory and analgesic activity. J. Invest. Dermatol., 86, 465Google Scholar
  52. 52.
    Atkinson, J.G., Guindon, Y. and Lau, C.K. (1985). Lipoxygenase inhibitors. Eur. Pat. Appl. EP 146243A1 (1985), Chem. Abstr., 103, 21515fGoogle Scholar
  53. 53.
    Khandwala, A., Coutts, S., Amin, D. and Sutherland, C. (1984). Rev. 5901-A specific inhibitor of 5-lipoxygenase: comparison of in vitro activity profile with non-steroidal antiinflammatory drugs. Abstr., 183 (Theme 26). III Internal Congress of Inflammation. September 3–7, ParisGoogle Scholar
  54. 54.
    Niemers, E., Gruetzmann, F., Mardin, M., Brusse, W.D. and Meyer, H. (1984). 4H-1, 4-benzothiazine lipoxygenase inhibitors. Ger. Offen. DE 3, 229, 121 (1984), Chem. Abstr.,100, 209852gGoogle Scholar
  55. 55.
    Niemers, E., Gruetzmann, R., Mardin, M., Brusse, W.D. and Meyer, H. (1984). Annellated 4H-1, 4-benzothiazine lipoxygenase inhibitors. Ger. Offen. DE 3, 229, 122 (1984). Chem. Abstr., 100, 185787mGoogle Scholar
  56. 56.
    Momose, D. (1986). Halocarboxanilides as antiallergics. Japan Kokai Tokkyo Koho JP 60, 146, 856 (1985), Chem. Abstr., 104, 33891kGoogle Scholar
  57. 57.
    Momose, D., Naito, A. and Kitazawa, M. (1985). Halocarboxanilide derivatives as antiallergics. Jpn. Kokai Tokkyo Koho JP 60, 146, 857. Chem. Abstr, 104, 33892mGoogle Scholar
  58. 58.
    Steggles, D.J. and Verge, J.P. (1986).1H-tetrazole-5-carboxamides and their pharmaceutical use. Eur. Pat. Appl. EP 147, 973 (1985), Chem. Abstr.,104, 340085nGoogle Scholar
  59. 59.
    Baumann, J., Bruchhausen, F.V. and Wurm, G. (1980). Flavonoids and related compounds as inhibitors of arachidonic acid peroxidation. Prostaglandins,20, 627–639PubMedGoogle Scholar
  60. 60.
    Yamashita, A. (1985). Substituted naphthalenes, indoles, benzofurans, and benzothiophenes as lipoxygenase inhibitors. Eur. Pat. Appl. EP 146, 348 (1985), Chem. Abstr., 103, 196418eGoogle Scholar
  61. 61.
    Teikoku Hormone Mfg. Co. Ltd. (1984). Dibenzazepine-2-acetic acids. Jpn. Kokai Tokkyo Koho JP 58, 146, 568 (1983), Chem. Abstr., 100, 85603eGoogle Scholar
  62. 62.
    Mardin, M., Sunderman, R., Hoffmeister, F., Busse, W.D., Horstmann, H. and Raddatz, S. (1983). Pyrazolooxazines, -thiazines, -quinolines, and their use as drugs. Chern. Abstr. 99, 175781bGoogle Scholar
  63. 63.
    Bailey, B., Dallob, A., Dougherty, H., Bonney, R., Humes, J., Tishler, A., Davies, P., Goldenberg, M. and Moore, V. (1986). A dual cyclooxygenase/5-lipoxyenase inhibitor. Presented at the 6th International Conference on Prostaglandins and Related Compounds. (Abstr. 406). June 3–6, Florence, ItalyGoogle Scholar
  64. 64.
    Rapoport, S., Haertel, B. and Hausporf, G. (1984). Methionine sulfoxide formation: the cause of self-inactivation of reticulocyte lipoxygenase. Eur. J. Biochem., 139, 573–576PubMedGoogle Scholar
  65. 65.
    Musser, J.H. and Chakraborty, U.R. (1984). Antiinflammatory and antiallergic benzyl phenyl ethers. Eur. Pat. Appl. EP 110405 (1984), Chem. Abstr, 101, 170878pGoogle Scholar
  66. 66.
    Copp, F.C., Islip, P.J. and Tateson, J.E. (1984). 3-N-Substituted-amino-1-(3-(trifluoromethyl)phenyl)-2- pyrazolines have enhanced activity against arachidonate 5-lipoxygenase and cyclooxyenase. Biochem. Pharmacol., 33, 339–340PubMedGoogle Scholar
  67. 67.
    Blackwell, G.J. and Flower, R.J. (1978). 1-Phenyl-3-pyrazolidone: an inhibitor of arachidonate oxidation in lung and platelets. Br. J. Pharmacol., 63, 360PPubMedGoogle Scholar
  68. 68.
    Blackwell, G.J. and Flower, R.J. (1978). 1-Phenyl-3-pyrazolidone: an inhibitor of cyclooxygenase and lipoxygenase pathways in lung and platelets. Prostaglandins, 16, 417–425PubMedGoogle Scholar
  69. 69.
    Robak, J. and Dunniec, Z. (1982). The influence of some 3-amino-2-pyrazoline derivatives on cyclooxygenase and lipoxidase activities. Biochem. Pharmacol., 31, 1955–1959PubMedGoogle Scholar
  70. 70.
    Appleton, R.A., Burford, S.C., Hardern, D.N. and Wilkinson D. (1986). Antiinflammatory 3-aminopyrazoles. Australian Patent AU 8542275A,Eur. Pat. Appl. EP 178035A1 (1986). Chem. Abstr., 105, 42796fGoogle Scholar
  71. 71.
    Magro, A.M. and Hurtado, I. (1983). The orally active antiallergic compound, LC-6 (trans2,3b,4,5,7,8b,9, 10-octahydronaphtho(1,2-C:5,6-C)dipyrazole) inhibits the arachidonate lipoxygenase enzyme. J. Immunopharmacol., 5, 191–202PubMedGoogle Scholar
  72. 72.
    Strasser, T., Fischer, S. and Weber, P.C. (1985). Inhibition of leukotriene B4 formation in human neutrophils after oral nafazatrom (BAY g 6575).Biochem. Pharmacol., 34, 1891–1894PubMedGoogle Scholar
  73. 73.
    Bayer, A.G. (1985). Therapeutic pyrazolone derivatives as lipoxygenase inhibitors. Jpn. Kokai Tokkyo Koho JP 59, 175, 469 (1984), Chem. Abstr.,102, 56154vGoogle Scholar
  74. 74.
    Fruchtmann, R., Horstmann, H., Opitz, W., Pelster, B., Raddatz, S. and Mardin, M. (1984). Pyrazolo (4,3-b) (1,4)oxazines and their use as lipoxygenase inhibitors. Ger. Offen. DE 3246148A1 (1984), Chem. Abstr., 101, 171270wGoogle Scholar
  75. 75.
    Busse, W.D., Krauthausen, E. and Mardin, M. (1983). Sulfenamides for use in pharmaceuticals. Chem. Abstr., 98, 143446jGoogle Scholar
  76. 76.
    Tihanyi, E., Fehér, O., Gàl, M., Janàky, J., Tolnay, P. and Sebestyén, L. (1986). Pyrazolecarboxylic-acid hydrazides as antiinflammatory agents new selective lipoxygenase inhibitors. Eur. J. Med. Chem. — Chim. Ther., 19, 433–439Google Scholar
  77. 77.
    Bertez, C., Miguel, M., Coquelet, C., Sincholle, D. and Bonne, C. (1984). Dual inhibition of cyclooxygenase and lipoxygenase by 2 acetyl thiophene 2 thizolyl hydrazone CBS-1108 and effect on leukocyte migration in-vivo. Biochem. Pharmacol., 33, 1757–1762PubMedGoogle Scholar
  78. 78.
    Bertez, C., Conduzorgues, J.P., Sincholle, D. and Bonne, C. (1984). CBS1114(N-phenylbenzamidrazone chloride), a dual inhibitor of cyclooxygenase and lipoxygenase. Abstract 115. (Theme 26). Presented at III International Congress of Inflammation, September 3–7, ParisGoogle Scholar
  79. 79.
    Wallach, D.P. and Brown, V.R. (1981). A novel preparation of human platelet lipoxygenase. Characteristics and inhibition by a variety of phenyl hydrazones and comparisons with other lipoxygenases. Biochim. Biophys. Acta,663, 361–372PubMedGoogle Scholar
  80. 80.
    Sun, F.F. and McGuire, J.C. (1983).Inhibition of human neutrophil arachidonate 5lipoxygenase by 6,9-deepoxy-6,9-phenylimino-6,8 prostaglandin I1 (U-60257). Prostaglandins,26, 211–221PubMedGoogle Scholar
  81. 81.
    Guindon, Y., Gillard, J.W., Yoakim, C., Jones, T.R. and Fortin, R. (1986). Indole-2-alkanoic acids and their use as prostaglandin antagonists. Eur. Pat. Appl. EP 166591A2 (1986), Chem. Abstr., 105, 78827fGoogle Scholar
  82. 82.
    Teikoku Hormone Mfg. Co. Ltd. (1984). 1-Substituted-2-phenylindoles. Jpn. Kokai Tokkyo Koho JP58, 162, 573 (1983), Chem. Abstr., 100, 68179uGoogle Scholar
  83. 83.
    Tahara, I., Ikebe, T., Maruyama, Y., Yaoka, O. and Miura, Y. (1986). 3-Indolecarboxamide compounds. Eur. Pat. Appl. EP 150, 505 (1985), Chem. Abstr.,104, 5787nGoogle Scholar
  84. 84.
    Boctor, A.M., Eickholt, M.M., Hovinga, M.E. and Pugsley, T.A. (1984). Modulation of arachidonic metabolism by the anti-allergy compound CI-922 (4H-furo(3,2-B)indole2-carboxamide, 3,7-dimethoxy-4-phenyl-N-1H-tetrazole-5-y1). Pharmacologist, 26,155 (Abstr. 137)Google Scholar
  85. 85.
    Corell, T., Hasselmann, G., Splawinski, J. and Wojtaszek, B. (1983). Fenflumizole: interactions with the arachidonic acid cascade. Acta Pharmacol. Toxicol., 53, 297–303Google Scholar
  86. 86.
    Beetens, J.R., Loots, W., Somers, Y., Coene, M.C. and DeClerck, F. (1986). Ketoconazole inhibits the biosynthesis of leukotrienes in vitro and in vivo. Biochem. Pharmacol., 35, 883–891PubMedGoogle Scholar
  87. 87.
    Boot, J.R., Sweatman, W.J.F., Cox, B.A., Stone, K. and Dawson, W. (1982). The antiallergic activity of benoxaprofen (2-(4-chlorophenyl)-a-methyl-5-benzoxazole acetic acid), a lipoxygenase inhibitor. Int. Arch. Allergy App). Immunol.,67, 340–343Google Scholar
  88. 88.
    Harvey, J., Parish, H., Ho, P.P.K., Boot, J.R. and Dawson, W. (1983). The preferential inhibition of 5-lipoxygenase formation by benoxaprofen. J. Pharm. Pharmacol., 35, 44–45PubMedGoogle Scholar
  89. 89.
    Walker, J.R. and Dawson, W. (1979). Inhibition of rabbit PMN lipoxygenase activity by benoxaprofen. J. Pharmacol., 31, 778–779Google Scholar
  90. 90.
    Busse, W.D., Krauthausen, E. and Mardin, M. (1983). Use of disulfides as lipoxygenase inhibitors and pharmaceuticals containing them. Ger. Offen. DE 3, 118, 128A1 (1982), Chem. Abstr., 98, 95663dGoogle Scholar
  91. 91.
    Egan, R.W. and Gale, P.H. (1985). Inhibition of mammalian 5-lipoxygenase by aromatic disulfides. J. Biol. Chem., 260, 11554–11559PubMedGoogle Scholar
  92. 92.
    Egan, R.W., Tischler, A.N., Baptista, E.M., Ham, E.A., Soderman, D.D. and Gale, P.H. (1983). Specific inhibition and oxidative regulation of 5-lipoxygenase. In Samuelsson, R., Ramwell, P.W. and Paoletti, R. (eds.) Advances in Prostaglandin, Thromboxane and Leukotriene Research. Vol. 11, pp. 151–157. (New York: Raven Press)Google Scholar
  93. 93.
    Carter, G.W., Dyer, R. and Young, P. (1985). Dipyridamole: a potent and specific 5-lipoxygenase inhibitor. Fed. Proc., 44, 904 (Abstr. 2880)Google Scholar
  94. 94.
    Lammattina, J.L. (1985). 2-Amino-5-hydroxy-4-methylpyrimidine derivatives. Eur. Pat. Appl. EP 138, 464A2 (1985). Chem. Abstr., 103, 142000uGoogle Scholar
  95. 95.
    Kitamura, S., Hashizume, K., Iida, T., Miyashita, E., Shirahata, K. and Kase, H. (1986). Studies on lipoxygenase inhibitors. II. KF8940 (2N-heptyl-4-hydroxyquiniline-N-oxide), a potent and selective inhibitor of 5-lipoxygenase, produced by Pseudomonas methanica. J. Antibiot., 39, 1160–1166Google Scholar
  96. 96.
    Schulte, K., Puetter, S. and Loew, D. (1986). Antiinflammatory pharmaceutical. Ger, Offen. DE 3, 409, 415 (1985), Chem. Abstr., 104, 33897sGoogle Scholar
  97. 97.
    Clémence, F., LeMartret, O., Delevallée, F. and Benzoni, J. (1984). New 4-hydroxy-3quinolinecarboxamides, potent inhibitors of both lipoxygenase and cyclooxygenase with anti-arthritic activities. Presented at the VIIIth International Symposium on Medicinal Chemistry, August 27–31, Uppsala, SwedenGoogle Scholar
  98. 98.
    Ahnfelt-Ronne, I. and Arrigoni-Martelli, E. (1980). A new anti-inflammatory compound timegadine N-cyclohexyl-N’-4–2-methylquinolyl- N’-2-thiazolylguanidine which inhibits both prostaglandin and 12-hydroxyeicosatetraenoic acid (12-HETE) formation. Biochem. Pharmacol., 29, 3265–3270PubMedGoogle Scholar
  99. 99.
    Durette, P.L. and Gallapher, T.F. (1985). Lipoxygenase inhibitors. United States Patent: US 4526999 A, 1985 Google Scholar
  100. 100.
    Kitamura, S., Lida, T., Shirahata, K. and Kase, H. (1986). Studies on lipoxygenase inhibitors. I. MY3–469 (3-methoxytropolone) a potent and selective inhibitor of 12-lipoxygenase, produced by Streptoverticillium hadonense KY11449. J. Antibiot., 39, 589–593PubMedGoogle Scholar
  101. 101.
    Mathews, W.R. and Murphy, R.C. (1982). Inhibition of leukotriene biosynthesis in mastocytoma cells by diethylcarbamazine. Biochem. Pharmacol., 31, 2129–2132PubMedGoogle Scholar
  102. 102.
    Piper, P.J. and Temple, D.M. (1981). The effect of lipoxygenase inhibitors and diethylcarbamazine on the immunological release of slow reacting substance of anaphylaxis (SRS-A) from guinea pig chopped lung. J. Pharm. Pharmacol.,33, 384–386PubMedGoogle Scholar
  103. 103.
    Bach, M.K. and Brashler, J.R. (1986).Inhibition of the leukotriene synthetase and rat basophil leukemia cells by diethylcarbamazine, and synergism between diethylcarbamazine and piriprost, a 5-lipoxygenase inhibitor. Biochem. Pharmacol.,35, 425–433PubMedGoogle Scholar
  104. 104.
    Stenson, W.F. and Lobos, E. (1982). Sulfasalazine inhibits the synthesis of chernotactic lipids by neutrophils. J. Clin. Invest., 69, 494–497PubMedGoogle Scholar
  105. 105.
    Evans, J.F., Dupuis, P. and Ford-Hutchinson, A.W. (1985). Purification and characterization of leukotriene A4 hydrolase from rat neutrophils. Biochim. Biophys. Acta, 840, 45–50Google Scholar
  106. 106.
    Evans, J., Nathaniel, D., Charleson, S., Léveillé, C., Zamboni, R., Leblanc, Y., Frenette, R., Fitzsimmons, B.J., Leger, S., Hamel, P. and Ford-Hutchinson, A.W. (1986). Neutrophil LTA, hydrolases and leukotriene B, receptors: effects of leukotriene epoxides and their enzymatic products. Prostagl. Leuk. Med., 23, 167–171Google Scholar
  107. 107.
    Evans, J.F., Nathaniel, D.J., Zamboni, R.J. and Ford-Hutchinson, A.W. (1985). Leukotriene A,. A poor substrate but a potent inhibitor of rat and human neutrophil leukotriene A, hydrolase. J. Biol. Chem.,260, 10966–10970PubMedGoogle Scholar
  108. 108.
    Bach, M.K., Brashler, J.R., Peck, R.E. and Morton, D.R. (1984). Leukotriene C synthetase, a special glutathione S-transferase: properties of the enzyme and inhibitor studies with special reference to the mode of action of U-60,257, a selective inhibitor of leukotriene synthesis. J. Allergy Clin. Immunol.,74, 353–357PubMedGoogle Scholar
  109. 109.
    O’Donnell, M. and Welton, A.F. (1984). Pharmacologic properties of FPL 55712 administered by aerosol. Agents Actions, 14, 43–48PubMedGoogle Scholar
  110. 110.
    Chand, N. (1979). FPL-55712 an antagonist of slow reacting substance of anaphylaxis (SRS-A): a review. Agents Actions, 9, 133–140PubMedGoogle Scholar
  111. 111.
    Jones, T., Denis, D., Hall, R. and Ethier, D. (1983). Pharmacological effects of leukotrienes C4, D4, E4, F4 on guinea pig trachealis: interaction with FPL-55712. Prostaglandins,26, 833–843PubMedGoogle Scholar
  112. 112.
    Appleton, R.A., Bantick, J.R., Chamberlain, T.R., Hardern, D.N., Lee, T.B. and Pratt, A.D. (1977). Antagonists of slow reacting substance of anaphylaxis. Synthesis of a series of chromone-2-carboxylic acids. J. Med. Chem., 20, 371–379PubMedGoogle Scholar
  113. 113.
    Holroyde, M.C. and Ghelani, A.M. (1983). Kinetics of action of two leukotriene antagonists on guinea pig ileum. Eur. J. Pharmacol., 90, 251–255PubMedGoogle Scholar
  114. 114.
    Oxford, A.W. and Ellis, F. (1982). Phenoxyalkoxyphenyl derivatives. U.K. Pat. Appl. GB 2058785A (2981). Chem. Abstr.,96, 51977pGoogle Scholar
  115. 115.
    Buckle, D.R., Outred, D.J., Ross, J.W., Smith, H., Smith, R.J. and Spicer, B.A. (1979). Aryloxyalkyloxy-and aralkyloxy-4-hydroxy-3-nitrocoumarins which inhibit histamine release in the rat and also antagonize the effects of a slow reacting substance of anaphylaxis. J. Med. Chem., 22, 158–168PubMedGoogle Scholar
  116. 116.
    Snyder, D.W., Bernstein, P.R. and Krell, R.D. (1985). Pharmacology of chemically stable analogs of peptide leukotrienes (LT). Fed. Proc., 44, 901 (Abstr. 2863)Google Scholar
  117. 117.
    Weichman, B.M., Wasserman, M.A., Holden, D.A., Osbom, R.R., Woodward, D.F., Ku, T.W. and Gleason, J.G. (1983). Antagonism of the pulmonary effects of the peptidoleukotrienes by a leukotriene D, analog. J. Pharmacol. Exp. Ther.,227, 700–705PubMedGoogle Scholar
  118. 118.
    Gleason, J.G., Ku, T.W., Kinzig, C.M., McCarthy, M.E., Perchonock, C.D., Kuzinskas, I., Berkowitz, B. and Weichman, B.M. (1984). In the Second SCI-RSC Medicinal Chemistry Symposium,257–267 (Special Publication 50: London: Royal Society of Chemistry)Google Scholar
  119. 119.
    Perchonock, C.D., Uzinskas, I., Ku, T.W., McCarthy, M.E., Bondinell, W.E., Volpe, B.W., Gleason, J.G., Weichman, B.M., Muccitelli, R.M., DeVan, J.F., Tucker, S.S., Vickery, L.M. and Wasserman, M.A. (1985). Synthesis and LTD4-antagonist activity of desamino-2nor-leukotriene analogs. Prostaglandins,29, 75–81PubMedGoogle Scholar
  120. 120.
    Saksena, A.K., Green, M.J., Mangiaracina, P., Wong, J.K., Kreutner, W. and Gulbenkian, A.R. (1985). Synthesis of 7,8-acetylenic analogs of hexahydroleukotriene-E4 with agonist and antagonist activities: convenient stereoselective routes to E- and Z-enzymes. Synthesis of 4,4’ -(4E,6Z,9Z-pentadecatrien-2-ynylidenedithio) dibutanoic acid with leukotriene-like activity: novel acetylenic acetals and dithioacetals as antagonists of leukotriene C, Tetrahedron Lett., 26, 6423–6426 and 6427–6430Google Scholar
  121. 121.
    Fleisch, J.H., Rinkema, L.E., Haisch, K.D., Swanson-Bean, D., Goodson, T., Ho, P.P.K. and Marshall, W.S. (1985). LY171883, 1-[2-hydroxy-3-propyl-4-(IH-tetrazo-5-yl) butoxy] phenyl ethanol, an orally active leukotriene D4 antagonist. J. Pharmacol. Exp. Ther., 233, 148–157PubMedGoogle Scholar
  122. 122.
    Young, R.N., Jones, T.R., Atkinson, J.G., Bélanger, P., Champion, E., Denis, D., DeHaven, R.N., Ford-Hutchinson, A.W., Fortin, R., Frenette, R., Gauthier, J.Y., Gillard, J., Guindon, Y., Kakushima, M., Masson, P., Maycock, A., McFarlane, C.S., Piechuta, H., Pong, S.S., Rokach, J., Williams, H., Yoakim, C. and Zamboni, R. (1987). Novel arylthio-and arylsulfonylpropyloxyacetophenones: design and synthesis of L-648,051 and L-649,923, potent antagonists of leukotriene D4. In Samuelsson, B., Paoletti, R. and Ramwell, P.W. (eds.) Advances in Prostaglandin, Thromboxane and Leukotriene Research. Vol. I7A. pp. 544–548. (New York: Raven Press)Google Scholar
  123. 123.
    Obata, T., Katsube, N., Miyamoto, T., Toda, M., Okegawa, T., Nakai, H., Kosuge, S., Konno, M., Arai, Y. and Kawasaki, A. (1985). New antagonists of leukotrienes: ONORS-411 and ONO-RS-347. In Hayaishi, O. and Yamamoto, S. (eds.) Advances in Prostaglandin, Thromboxane and Leukotriene Research. Vol. 15, pp. 229–231. (New York: Raven Press)Google Scholar
  124. 124.
    Toda, M., Nakai H., Kosuge, S., Konno, M., Arai, Y., Miyamoto, T., Obata, T., Katsube, N. and Kawasaki, A. (1985). A potent antagonist of the slow reacting substance of anaphylaxis. In Hayaishi, O. and Yamamoto, S. (eds.) Advances in Prostaglandins, Thromboxane and Leukotriene Research. Vol. 15, pp. 307–308. (New York: Raven Press)Google Scholar
  125. 125.
    Perchonock, C.D., McCarthy, M.E., Erhard, K.F., Gleason, J.G., Wasserman, M.A., Muccitelli, R.M., DeVan, J.F., Tucker, S.S., Vickery, L.M., Kirchner, T., Weichman, B.M., Mong, S., Crooke, S.T. and Newton, J.F. (1985). Synthesis and pharmacological characterization of 5-(2-dodecylphenyl)-4,6-dithianonanedioic acid and 5-(2-(8-phenyloctyl)phenyl)-4,6-dithianonanedioic acid: prototypes of a novel class of leukotriene antagonists. J. Med. Chem.,28, 1145–1147PubMedGoogle Scholar
  126. 126.
    Saijo, T., Kuiriki, H., Ashida, Y., Makino, H. and Maki, Y. (1985). Inhibition of amoxanox (AA-673) of the immunoloically, leukotriene D4- or platelet-activating factor-stimulated bronchoconstriction in guinea pigs and rats. Int. Arch. Allergy Appl. Immunol., 77, 315–321PubMedGoogle Scholar
  127. 127.
    Mong, S., Hall, R.F., Gleason, J.C. and Crooke, S.T. (1986). SKF 104353, an antagonist binding to human and guinea pig lung leukotriene D4 (LTD4) receptors and inhibition of cyclooxygenase dependent effect. Presented at the 6th International Conference on Prostaglandins and Related Compounds, June 3–6, Florence, Italy (Abstr. 356)Google Scholar
  128. 128.
    Von Sprecher, A., Ernst, I., Main, I., Beck, A., Breitenstein, W., Marki, J., Poray, M.A., Wenk, P., Niederhauser, U., Kuhan, M. and Sallman, A. (1986). Novel leukotriene antagonists: structure activity of analogs of LTD,. Replacement of the 1-carboxylic group by a methyl group (‘Methyl Principle’) results in leukotriene antagonists and phospholipase inhibitors. Presented at the 6th International Conference on Prostaglandins and Related Compounds,June 3–6, Florence, ItalyGoogle Scholar
  129. 129.
    Ono Pharmaceutical Co. Ltd. (1984). Leukotriene B4-related compounds. Jpn. Kokai Tokkyo Koho JP5995249 (1984), Chem. Abstr., 101, 230229qGoogle Scholar
  130. 130.
    Showell, H.J., Otterness, I.G., Marfat, A. and Corey, E.J. (1982). Inhibition of leukotriene Ba-induced neutrophil degranulation by leukotriene B4-dimethylamide. Biochem. Biophys. Res. Commun,, 106, 741–747PubMedGoogle Scholar
  131. 131.
    Namiki, M., Igarashi, Y., Sakamoto, K., Nakamura, T. and Koga, Y. (1986). Pharmacological profiles of a potential LTB4-antagonist. SM-9064. Biochem. Biophys. Res. Commun., 138, 540–546PubMedGoogle Scholar

Copyright information

© MTP Press Limited 1988

Authors and Affiliations

  • B. J. Fitzsimmons
  • J. Rokach

There are no affiliations available

Personalised recommendations