The properties of A-69412: a small hydrophilic 5-lipoxygenase inhibitor.

A compound which inhibits leukotriene biosynthesis could be clinically useful in treating several allergic and inflammatory diseases. One site for such inhibition is at the enzyme 5-lipoxygenase. Most inhibitors of this enzyme thus far described are poorly bioavailable. A-69412 is a small, relatively hydrophilic compound of the N-hydroxyurea class, which exhibits minimal plasma protein binding (6-12%). The compound was found to be a potent long-acting inhibitor of leukotriene formation in vivo in the rat (oral ED50 = 5 mg/kg) and ex vivo in several species. In addition, the compound exhibits excellent bioavailability in dogs and monkeys with a relatively long elimination half-life in both the species (6 and 3 h, respectively). The biochemical activity and pharmacological profile of A-69412 indicates its potential utility in asthma and ulcerative colitis, and possibly other inflammatory and allergic conditions.