These compounds underwent extensive in vitro investigation revealing dual 5-LOX/sEH inhibitors, with 73 showing the most promising activity (IC50s of 0.41 ±0.01 and 0.43 ± 0.10 μM for 5-LOX and sEH, respectively).When challenged in vivo in zymosan-induced peritonitis and experimentalasthma in mice, compound 73 showed remarkable anti-inflammatoryefficacy. The gene discussed is ALOX5; the disease is peritonitis.