Dibenzoxepinone hydroxylamines and hydroxamic acids: dual inhibitors of cyclooxygenase and 5-lipoxygenase with potent topical antiinflammatory activity

  • J Med Chem. 1996 Jan 5;39(1):246-52. doi: 10.1021/jm950563z.
R R Hamer  1 ,  J J Tegeler ,  E S Kurtz ,  R C Allen ,  S C Bailey ,  M E Elliott ,  L Hellyer ,  G C Helsley ,  P Przekop ,  B S Freed ,  J White ,  L L Martin
Affiliations
  • 1. Hoechst-Roussel Pharmaceuticals Inc., Somerville, New Jersey 08876, USA.
PMID: 8568814 DOI: 10.1021/jm950563z
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.

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