Synthesis and antiinflammatory/analgesic activities of 11H-dibenzo[b, e,][1,4]dioxepinacetic acids

J Med Chem. 1986 Aug;29(8):1436-41. doi: 10.1021/jm00158a020.


A new class of tricyclic arylacetic acids was synthesized and evaluated as antiinflammatory/analgesic agents as well as inhibitors of prostaglandin synthetase. 11H-Dibenzo[b,e][1,4]dioxepin-2-, -3, -7, and -8-acetic and alpha-methylacetic acids and their derivatives were prepared by cyclization of diaryl ether precursors or by condensation of catechol and an aryl dihalide. The most potent compound in the carrageenan foot edema assay was alpha-methyl-11H-dibenzo[b,e][1,4]dioxepin-8-acetic acid (1 mg/kg = 43% inhibition). The most potent enzyme inhibitors were the 2-acetic acid and the alpha-methyl-7-acetic acid (IC50 = 0.1 microM). Some of these compounds were also found to be highly ulcerogenic.

MeSH terms

  • Analgesics / chemical synthesis*
  • Analgesics / therapeutic use
  • Animals
  • Anti-Inflammatory Agents / chemical synthesis*
  • Anti-Inflammatory Agents / therapeutic use
  • Benzoxepins / chemical synthesis*
  • Benzoxepins / pharmacology
  • Edema / drug therapy
  • Gastrointestinal Hemorrhage / drug therapy
  • Male
  • Mice
  • Pain / drug therapy
  • Rats
  • Rats, Inbred Strains
  • Structure-Activity Relationship


  • Analgesics
  • Anti-Inflammatory Agents
  • Benzoxepins