New cyclooxygenase-2/5-lipoxygenase inhibitors. 1. 7-tert-buty1-2,3-dihydro-3,3-dimethylbenzofuran derivatives as gastrointestinal safe antiinflammatory and analgesic agents: discovery and variation of the 5-keto substituent

J Med Chem. 1998 Mar 26;41(7):1112-23. doi: 10.1021/jm970679q.


A series of 5-keto-substituted 7-tert-buty1-2,3-dihydro-3,3- dimethylbenzofurans (DHDMBFs) were prepared and evaluated as potential nonsteroidal antiinflammatory and analgesic agents. Interest in this class of compounds arose when a DHDMBF was found to be an active metabolite of the di-tert-butylphenol antiinflammatory agent tebufelone. We have now found that a variety of 5-keto-substituted DHDMBFs have good in vivo antiinflammatory and analgesic activity after oral administration. These compounds inhibit both cyclooxygenase (COX) and 5-lipoxygenase (5-LOX) in vitro. The cyclooxygenase inhibition was found to be selective for the cyclooxygenase-2 isoform, and this combination of COX-2/5-LOX inhibition may be responsible for the gastrointestinal safety of compounds such as 30.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / chemical synthesis*
  • Anti-Inflammatory Agents / chemistry
  • Anti-Inflammatory Agents / pharmacology
  • Benzofurans / chemical synthesis*
  • Benzofurans / pharmacology
  • Blood Platelets / drug effects
  • Blood Platelets / enzymology
  • Carrageenan / adverse effects
  • Cyclooxygenase Inhibitors / chemical synthesis*
  • Cyclooxygenase Inhibitors / chemistry
  • Cyclooxygenase Inhibitors / pharmacology
  • Edema / chemically induced
  • Edema / drug therapy
  • Humans
  • Lipoxygenase Inhibitors*
  • Male
  • Rats
  • Rats, Inbred Lew
  • Rats, Sprague-Dawley


  • Anti-Inflammatory Agents
  • Benzofurans
  • Cyclooxygenase Inhibitors
  • Lipoxygenase Inhibitors
  • Carrageenan