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  • Title: The discovery and development of zileuton: an orally active 5-lipoxygenase inhibitor.
    Author: Bell RL, Young PR, Albert D, Lanni C, Summers JB, Brooks DW, Rubin P, Carter GW.
    Journal: Int J Immunopharmacol; 1992 Apr; 14(3):505-10. PubMed ID: 1618602.
    Abstract:
    The enzyme 5-lipoxygenase is a key target in the effort to discover drugs which inhibit the pathophysiology associated with the formation of leukotrienes. The research efforts of these laboratories have focused on the discovery of direct enzyme inhibitors of 5-lipoxygenase. In particular, compounds with hydroxamate or N-hydroxyurea functionalities have proven to be potent inhibitors of leukotriene biosynthesis in vitro and more importantly in vivo. One of these compounds, zileuton (N-(1-benzo-[b]-thien-2-ylethyl)-N-hydroxyurea) has been shown recently to be an effective leukotriene inhibitor in man. The critical approaches and breakthroughs in the discovery and development of zileuton are described. In addition, some recent results with zileuton in animals and man are detailed.
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