Development of 2,3-Dihydro-6-(3-phenoxypropyl)-2-(2-phenylethyl)-5-benzofuranol (L-670,630) as a Potent and Orally Active Inhibitor of 5-Lipoxygenase

Article abstract of DOI:10.1021/jm00085a019

Leukotrienes are potent biological mediators of allergic and antiinflammatory diseases and are derived from arachidonic acid through the action of the 5-lipoxygenase.In this study, the syntheses and comparative biological activities of three series of 2,3-dihydro-2,6-disubstituted-5-benzofuranols with various substituents on position 3 are described.Compounds from each series were evaluated for their ability to inhibit the production of leukotriene B4 (LTB4) in human peripheral blood polymorphonuclear (PMN) leukocytes and the 5-lipoxygenase reaction in cell-free preparations from rat PMN leukocytes.The structure-activity relationships of each series in vitro and in vivo are presented.The bioavailability, metabolism, and toxicity profile of each series are discussed.The series with no substituent at position 3 was the most potent and among the compounds in that series 2,3-dihydro-6-(3-phenoxypropyl)2-(2-phenylethyl)-5-benzofuranol (46, L-670,630) was chosen for further development.