DIBENZOXEPINONE HYDROXYLAMINES AND HYDROXAMIC ACIDS - DUAL INHIBITORSOF CYCLOOXYGENASE AND 5-LIPOXYGENASE WITH POTENT TOPICAL ANTIINFLAMMATORY ACTIVITY

Hydroxylamine and hydroxamic acid derivatives of a known nonsteroidal antiinflammatory dibenzoxepine series display both cyclooxygenase (CO) and 5-lipoxygenase (5-LO) inhibitory properties. Many of these new du al CO15-LO inhibitors also exhibit potent topical antiinflammatory act ivity in the arachidonic acid-induced murine ear edema model. On the b asis of their promising profile of in vitro and in vivo activities, hy droxamic acids 24h, enz[b,e]oxepin-2-yl)-N-hydroxy-N-methylpropanamide (HP 977), and -(6,11-dihy-drodibenz[b,e]oxepin-2-yl)-N-hydroxy-N (P10 294), were selected as developmental candidates for the topical treatm ent of inflammatory skin disorders.