title: Dibenzoxepinone hydroxylamines and hydroxamic acids: dual inhibitors of cyclooxygenase and 5-lipoxygenase with potent topical antiinflammatory activity.
abstract: 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 dual CO/5-LO inhibitors also exhibit potent topical antiinflammatory activity in the arachidonic acid-induced murine ear edema model. On the basis of their promising profile of in vitro and in vivo activities, hydroxamic acids 24h, 3-(6,11-dihydro-11-oxodibenz[b,e]oxepin-2-yl)-N-hydroxy-N-++ +methylpropanamide (HP 977), and 25, 3-(6,11-dihydrodibenz[b,e]oxepin-2-yl)-N-hydroxy-N- methylpropanamide (P10294), were selected as developmental candidates for the topical treatment of inflammatory skin disorders.
authors.affiliation: Hoechst-Roussel Pharmaceuticals Inc., Somerville, New Jersey 08876, USA.
authors.forename: R R
authors.initials: RR
authors.lastname: Hamer
authors.forename: J J
authors.initials: JJ
authors.lastname: Tegeler
authors.forename: E S
authors.initials: ES
authors.lastname: Kurtz
authors.forename: R C
authors.initials: RC
authors.lastname: Allen
authors.forename: S C
authors.initials: SC
authors.lastname: Bailey
authors.forename: M E
authors.initials: ME
authors.lastname: Elliott
authors.forename: L
authors.initials: L
authors.lastname: Hellyer
authors.forename: G C
authors.initials: GC
authors.lastname: Helsley
authors.forename: P
authors.initials: P
authors.lastname: Przekop
authors.forename: B S
authors.initials: BS
authors.lastname: Freed
authors.forename: J
authors.initials: J
authors.lastname: White
authors.forename: L L
authors.initials: LL
authors.lastname: Martin
mesh_terms: D016475:3T3 Cells; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism; D016718:Arachidonic Acid / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D003990:Dibenzoxepins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015232:Dinoprostone / Q000032:analysis; D006877:Hydroxamic Acids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006893:Hydroxyeicosatetraenoic Acids / Q000032:analysis; D006898:Hydroxylamines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D016859:Lipoxygenase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D003990:Dibenzoxepins; C097779:HP 977; D006877:Hydroxamic Acids; D006893:Hydroxyeicosatetraenoic Acids; D006898:Hydroxylamines; D016859:Lipoxygenase Inhibitors; C097780:P 10294; D016718:Arachidonic Acid; C022022:5-hydroxy-6,8,11,14-eicosatetraenoic acid; D001094:Arachidonate 5-Lipoxygenase; D015232:Dinoprostone