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, Volume 34, Issue 1–2, pp 145–147 | Cite as

Leukotriene biosynthesis inhibition by aryl and aroyl substituted naphthoquinones

  • D. M. Roland
  • W. M. Macchia
  • K. S. Grim
  • E. F. Kimble
  • D. H. White
  • T. J. Kowalski
Design and Development of Drugs

Abstract

Naphthoquinones are known to inhibit 5-lipoxygenase. In particular, CGS 8515 (methyl 2-[(3,4-dihydro-3,4-dioxo-1-naphthalenyl)amino]benzoate) has been studied in detail. However this potent and selective 5-lipoxygenase inhibitor has a short duration of action and poor bioavailability. To improve the duration of action we have prepared a series of carbon substituted naphthoquinones. Several members of this series have demonstrated potentin vitro inhibition of 5-LO (IC50's<10−6M) and at doses of 1 mg/kg iv completely inhibited LTB4 production measured inex vivo A23187-stimulated blood from dogs. The duration of action measured by theex vivo assay was improved up to threefold over CGS 8515.

Keywords

Methyl Short Duration LTB4 Naphthoquinones Biosynthesis Inhibition 

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Copyright information

© Birkhäuser Verlag 1991

Authors and Affiliations

  • D. M. Roland
    • 1
  • W. M. Macchia
    • 1
  • K. S. Grim
    • 1
  • E. F. Kimble
    • 1
  • D. H. White
    • 1
  • T. J. Kowalski
    • 1
  1. 1.Research Department, Pharmaceuticals DivisionCIBA-GEIGY Corp.SummitUSA

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