Identification of benzofuran central cores for the inhibition of leukotriene A4 hydrolase

Leukotrienes (LT’s) are known to play a physiological role in inflammatory immune response. Leukotriene A4 hydrolase (LTA4H) is a cystolic enzyme that stereospecifically catalyzes the transformation of LTA4 to LTB4. LTB4 is a known pro-inflammatory mediator. This paper describes the identification and synthesis of substituted benzofurans as LTH4H inhibitors. The benzofuran series demonstrated reduced mouse and human whole blood LTB4 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 LTA4H inhibitor for the treatment of inflammatory diseases, such as asthma and inflammatory bowel disease (IBD).

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