Synthesis and topical antiinflammatory and antiallergic activities of antioxidant o-aminophenol derivatives

J Med Chem. 1994 Jun 24;37(13):1977-82. doi: 10.1021/jm00039a010.

Abstract

In order to develop novel compounds for topical use possessing antiallergic as well as antiinflammatory activities, a series of o-aminophenol derivatives bearing H1-antihistaminic structures were synthesized and their effects were investigated on lipid peroxidation in rat brain homogenates, antiinflammatory effection arachidonic acid- and 12-O-tetradecanoylphorbol-13- acetate-induced mouse ear edema and antiallergic effect on 48-h homologous passive cutaneous anaphylaxis in rats. Furthermore, the effects of these compounds on delayed-type hypersensitivity reaction in mice were examined. Several N-monosubstituted amino-4-methylphenols were found to exert potent inhibitory activities in all of these assays. Of these compounds, 4m was chosen for further development as AD0261.

MeSH terms

  • Administration, Topical
  • Aminophenols / administration & dosage
  • Aminophenols / chemical synthesis
  • Aminophenols / chemistry
  • Aminophenols / pharmacology*
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
  • Anti-Inflammatory Agents, Non-Steroidal / chemical synthesis
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Antioxidants / chemical synthesis
  • Antioxidants / chemistry
  • Antioxidants / pharmacology
  • Arachidonic Acid / pharmacology
  • Brain / drug effects
  • Ear
  • Edema / drug therapy
  • Guinea Pigs
  • Histamine H1 Antagonists / administration & dosage
  • Histamine H1 Antagonists / chemical synthesis
  • Histamine H1 Antagonists / pharmacology*
  • Hypersensitivity, Delayed / drug therapy*
  • Lipid Peroxidation / drug effects*
  • Male
  • Mice
  • Mice, Inbred ICR
  • Passive Cutaneous Anaphylaxis / drug effects*
  • Rats
  • Rats, Sprague-Dawley
  • Skin Tests
  • Tetradecanoylphorbol Acetate / pharmacology

Substances

  • Aminophenols
  • Anti-Inflammatory Agents, Non-Steroidal
  • Antioxidants
  • Histamine H1 Antagonists
  • 2-aminophenol
  • Arachidonic Acid
  • Tetradecanoylphorbol Acetate