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Leukotriene biosynthesis inhibition by aryl and aroyl substituted naphthoquinones

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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<10−6 M) 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.

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Authors and Affiliations

  1. Research Department, Pharmaceuticals Division, CIBA-GEIGY Corp., 556 Morris Ave, 07901, Summit, NJ, USA

    D. M. Roland, W. M. Macchia, K. S. Grim, E. F. Kimble, D. H. White & T. J. Kowalski

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  1. D. M. Roland
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  2. W. M. Macchia
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  3. K. S. Grim
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  4. E. F. Kimble
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  5. D. H. White
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  6. T. J. Kowalski
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Roland, D.M., Macchia, W.M., Grim, K.S. et al. Leukotriene biosynthesis inhibition by aryl and aroyl substituted naphthoquinones. Agents and Actions 34, 145–147 (1991). https://doi.org/10.1007/BF01993262

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