New celecoxib derivatives as anti-inflammatory agents

J Med Chem. 2008 Jan 10;51(1):142-7. doi: 10.1021/jm070821f. Epub 2007 Dec 12.

Abstract

A series of 1,5-diarylpyrazoles with a substituted benzenesulfonamide moiety was synthesized and evaluated for cyclooxygenase (COX-1/COX-2) inhibitory activities. Some compounds, for example, (+/-)-2-[4-(5- p-tolyl-3-trifluoromethyl-pyrazole-1-yl)-benzenesulfonylaminooxy]-propionic acid 16 and its disodium salt 21, had a higher in vivo anti-inflammatory activity compared to celecoxib, despite having no in vitro COX-1 or COX-2 inhibitory activity. Their gastrointestinal side effect profile is essentially more favorable than that of celecoxib.

MeSH terms

  • Acetic Acid
  • Animals
  • Carrageenan
  • Celecoxib
  • Chronic Disease
  • Crystallization
  • Cyclooxygenase 1 / chemistry
  • Cyclooxygenase 1 / metabolism
  • Cyclooxygenase 2 / chemistry
  • Cyclooxygenase 2 / metabolism
  • Cyclooxygenase Inhibitors / chemical synthesis*
  • Cyclooxygenase Inhibitors / chemistry
  • Cyclooxygenase Inhibitors / pharmacology
  • Edema / drug therapy
  • Ethanol
  • Gastric Mucosa / drug effects
  • Gastric Mucosa / pathology
  • Hyperalgesia / drug therapy
  • Male
  • Pyrazoles / chemical synthesis*
  • Pyrazoles / chemistry
  • Pyrazoles / pharmacology
  • Rats
  • Rats, Wistar
  • Recombinant Proteins / chemistry
  • Stereoisomerism
  • Stomach Ulcer / chemically induced
  • Stomach Ulcer / pathology
  • Stomach Ulcer / prevention & control
  • Sulfonamides / chemical synthesis*
  • Sulfonamides / chemistry
  • Sulfonamides / pharmacology

Substances

  • Cyclooxygenase Inhibitors
  • Pyrazoles
  • Recombinant Proteins
  • Sulfonamides
  • Ethanol
  • Carrageenan
  • Cyclooxygenase 1
  • Cyclooxygenase 2
  • Celecoxib
  • Acetic Acid