The discovery of LY293111, a novel, potent and orally active leukotriene B4 receptor antagonist of the biphenylphenol class.

Abstract

Leukotriene B4 (LTB4) has been implicated as a key pro-inflammatory mediator in human diseases such as asthma, inflammatory bowel disease, psoriasis and arthritis (1). LTB4’s role in human disease is supported by the fact that via G-protein coupled receptor mediated events, this product of the 5-lipoxygenase pathway of arachidonic acid metabolism initiates granulocyte chemotaxis, aggregation, upregulation of adhesion molecules and the release of Superoxide and degradative enzymes (2). The existence of elevated concentrations of LTB4 in tissues or interstitial fluids of patients with inflammatory diseases also supports the role of LTB4 as a pro-inflammatory mediator (1). However, the presence of LTB4 associated with the clinical manifestations of these inflammatory diseases only indirectly implicates it as a major player in inflammatory processes. The delineation of LTB4’s role in inflammation requires the development of potent and selective LTB4 receptor antagonists.KeywordsInflammatory Bowel DiseaseReceptor BindingHuman NeutrophilArachidonic Acid MetabolismBioactive LipidThese 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.