Advertisement

Arylmethyl Phenyl Ethers

A New Class of Specific Inhibitors of 5-Lipoxygenase
  • Stephen M. Coutts
  • Atul Khandwala
  • Richard Van Inwegen
  • Utpal Chakraborty
  • John Musser
  • John Bruens
  • Navin Jariwala
  • Vernetta Dally-Meade
  • Richard Ingram
  • Thaddeus Pruss
  • Howard Jones
  • Edward Neiss
  • Ira Weinryb
Part of the GWUMC Department of Biochemistry Annual Spring Symposia book series (GWUN)

Abstract

Oxidative metabolites of arachidonic acid produced by the 5-lipoxygenase pathway are potent mediators of hypersensitivity and inflammation (see O’Flaherty, 1982; Lewis and Austen, 1984 for reviews). Their proposed roles in the pathophysiology of asthma, chronic inflammation, and psoriasis have prompted an intense search for specific inhibitors of their biosynthesis (Bach, 1984). Three years ago a program was initiated at Revlon Health Care Group to find compounds that would modulate the biosynthesis of leukotrienes or antagonize their spasmogenic actions on smooth muscle. In particular, we sought specific and stable inhibitors of the 5-lipoxygenase (5-LOX) enzyme, utilizing a cellular assay as our primary screening tool.

Keywords

Phenyl Ether Human Basophil Eicosatetraenoic Acid Primary Screening Tool Parenchymal Strip 
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. Bach, M.K., 1984, Prospects for the inhibition of leukotriene synthesis, Biochem. Pharmacol. 33:515–521.PubMedCrossRefGoogle Scholar
  2. Chang, W.C., Nakao, J., Orimo, H., and Murota, S., 1982, Effects of reduced glutathione on the 12-lipoxygenase pathways in rat platelets, Biochem. J. 202:771–776.PubMedGoogle Scholar
  3. Drazen, J.M., Austen, K.F., Lewis, R.A., Clark, D.A., Groto, G., Marafat, A., and Corey, E.J., 1980, Comparative airway and vascular activities of leukotrienes C-1 and D in vivo and in vitro, Proc. Natl. Acad. Sci. U.S.A. 77:4354–4358.PubMedCrossRefGoogle Scholar
  4. Flower, R.J., Cheung, H.S., and Cushman, D.W., 1973, Quantitative determination of prostaglandins and malondialdehyde formed by the arachidonate oxygenase (prostaglandin synthetase) system of bovine seminal vesicle, Prostaglandins 4:325–341.PubMedCrossRefGoogle Scholar
  5. Gordon, R.J., Travis, J., Godfrey, H.R., Sweeney, D, Wolf, P.S., Pruss, T.P., Neiss, E., Musser, J., Chakraborty, U., Jones, H., and Leibowitz, M., 1984, In vivo activity of a lipoxygenase inhibitor and leukotriene antagonist, REV 5901-A, Leukotrienes Prostaglandins 84:266.Google Scholar
  6. Khandwala, A., Coutts, S., and Weinryb, I., 1982, Antiallergic activity of tiaramide, Int. Arch. Allergy Appl. Immunol. 69:159–168.PubMedCrossRefGoogle Scholar
  7. Lewis, R.A., and Austen, K.F., 1984, The biologically active leukotrienes: Biosynthesis, metabolism, receptors, function and pharmacology, J. Clin. Invest. 73:889–897.PubMedCrossRefGoogle Scholar
  8. Marone, G., Hammarström, S., and Lichtenstein, L.M., 1980, An inhibitor of lipoxygenase inhibits histamine release from human basophils, Clin. Immunol. Immunopathol. 17:117–122.PubMedCrossRefGoogle Scholar
  9. O’Flaherty, J.T., 1982, Biology of disease: Lipid mediators of inflammation and allergy, Lab. Invest. 47:314–329.PubMedGoogle Scholar
  10. Peters, S.P., Siegel, M.I., Kagey-Sabotka, A., and Lichtenstein, L.M., 1981, Lipoxygenase products modulate histamine release in human basophils, Nature 292:455–457.PubMedCrossRefGoogle Scholar
  11. Vanderhoek, J.Y., Bryant, R.W., and Bailey, J.M., 1980, Inhibition of leukotriene biosynthesis by the leukocyte product 15-hydroxy-5,8,11,13-eicosatetraenoic acid, J. Biol. Chem. 255:10064–10066.PubMedGoogle Scholar
  12. Vanderhoek, J.Y., Bryant, R.W., and Bailey, J.M., 1982, Regulation of leukocyte and platelet lipoxygenases by hydroxyeicosanoids, Biochem. Pharmacol. 31:3463–3467.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1985

Authors and Affiliations

  • Stephen M. Coutts
    • 1
  • Atul Khandwala
    • 1
  • Richard Van Inwegen
    • 1
  • Utpal Chakraborty
    • 1
  • John Musser
    • 1
  • John Bruens
    • 1
  • Navin Jariwala
    • 1
  • Vernetta Dally-Meade
    • 1
  • Richard Ingram
    • 1
  • Thaddeus Pruss
    • 1
  • Howard Jones
    • 1
  • Edward Neiss
    • 1
  • Ira Weinryb
    • 1
  1. 1.Revlon Health Care GroupResearch and DevelopmentTuckahoeUSA

Personalised recommendations