Identification of benzofuran central cores for the inhibition of leukotriene A 4 hydrolase

Abstract Leukotrienes (LT’s) are known to play a physiological role in inflammatory immune response. Leukotriene A 4 hydrolase (LTA 4 H) is a cystolic enzyme that stereospecifically catalyzes the transformation of LTA 4 to LTB 4 . LTB 4 is a known pro-inflammatory mediator. This paper describes the identification and synthesis of substituted benzofurans as LTH 4 H inhibitors. The benzofuran series demonstrated reduced mouse and human whole blood LTB 4 levels in vitro and led to the identification one analog for advanced profiling. Benzofuran 28 showed dose responsive target engagement and provides a useful tool to explore a LTA 4 H inhibitor for the treatment of inflammatory diseases, such as asthma and inflammatory bowel disease (IBD).