New cyclooxygenase-2/5-lipoxygenase inhibitors. 3. 7-tert-butyl-2, 3-dihydro-3,3-dimethylbenzofuran derivatives as gastrointestinal safe antiinflammatory and analgesic agents: variations at the 5 position

J Med Chem. 1998 Aug 27;41(18):3515-29. doi: 10.1021/jm9802416.

Abstract

We report an expansion of the scope of our initial discovery that 5-keto-substituted 7-tert-butyl-2,3-dihydro-3,3-dimethylbenzofurans (DHDMBFs) are antiinflammatory and analgesic agents. Several other functional groups have been introduced at the 5 position: amides, amidines, ureas, guanidines, amines, heterocycles, heteroaromatics, and heteroaryl ethenyl substituents in the 5 position all provide active compounds. These compounds are dual cyclooxygenase (COX) and 5-lipoxygenase (5-LOX) inhibitors. They inhibit both COX-1 and COX-2 with up to 33-fold selectivity for COX-2.

MeSH terms

  • Analgesics* / chemical synthesis
  • Analgesics* / chemistry
  • Analgesics* / pharmacology
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal* / chemical synthesis
  • Anti-Inflammatory Agents, Non-Steroidal* / chemistry
  • Anti-Inflammatory Agents, Non-Steroidal* / pharmacology
  • Benzofurans* / chemical synthesis
  • Benzofurans* / chemistry
  • Benzofurans* / pharmacology
  • Carrageenan / toxicity
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors* / chemical synthesis
  • Cyclooxygenase Inhibitors* / chemistry
  • Cyclooxygenase Inhibitors* / pharmacology
  • Edema / chemically induced
  • Edema / drug therapy
  • Enzyme Inhibitors* / chemical synthesis
  • Enzyme Inhibitors* / chemistry
  • Enzyme Inhibitors* / pharmacology
  • Humans
  • Isoenzymes / metabolism*
  • Lipoxygenase Inhibitors*
  • Membrane Proteins
  • Prostaglandin-Endoperoxide Synthases / metabolism*
  • Rats
  • Structure-Activity Relationship

Substances

  • Analgesics
  • Anti-Inflammatory Agents, Non-Steroidal
  • Benzofurans
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase Inhibitors
  • Enzyme Inhibitors
  • Isoenzymes
  • Lipoxygenase Inhibitors
  • Membrane Proteins
  • Carrageenan
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • PTGS1 protein, human
  • PTGS2 protein, human
  • Prostaglandin-Endoperoxide Synthases
  • Ptgs1 protein, rat