Fenbufen based 3-[5-(substituted aryl)-1,3,4-oxadiazol-2-yl]-1-(biphenyl-4-yl)propan-1-ones as safer antiinflammatory and analgesic agents

Eur J Med Chem. 2009 Sep;44(9):3798-804. doi: 10.1016/j.ejmech.2009.04.009. Epub 2009 Apr 14.

Abstract

The synthesis of a series of 3-[5-(substituted aryl)-1,3,4-oxadiazol-2-yl]-1-(biphenyl-4-yl)propan-1-ones derived from 4-oxo-4-(biphenyl-4-yl)butanoic acid (fenbufen) is described. The structures of these compounds were supported by IR, (1)H NMR, mass spectrometric data and elemental analysis. These compounds were tested for their antiinflammatory, analgesic, ulcerogenic and lipid peroxidation actions. A few compounds were found to have very good antiinflammatory activity in carrageenan induced rat paw edema test, while a fair number of compounds showed significant analgesic activity in acetic acid induced writhing test. The newly synthesized compounds showed very low ulcerogenic action with reduced malondialdehyde (MDA) content, which is one of the byproducts of lipid peroxidation. In vitro COX-1 and COX-2 isozyme inhibition studies were also performed on some of the selected compounds. Compound 4i and 4h were found to be more selective towards COX-2 as indicated by COX-2 selectivity index of 36.06 and 29.05 (COX-2 IC(50)=1.5 microM and 1.8 microM) respectively.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics / adverse effects
  • Analgesics / chemical synthesis
  • Analgesics / chemistry*
  • Analgesics / pharmacology*
  • Animals
  • Anti-Inflammatory Agents / adverse effects
  • Anti-Inflammatory Agents / chemical synthesis
  • Anti-Inflammatory Agents / chemistry*
  • Anti-Inflammatory Agents / pharmacology*
  • Cyclooxygenase Inhibitors / pharmacology
  • Female
  • Lipid Peroxidation / drug effects
  • Male
  • Mice
  • Oxadiazoles / adverse effects
  • Oxadiazoles / chemical synthesis
  • Oxadiazoles / chemistry*
  • Oxadiazoles / pharmacology*
  • Pain Measurement / drug effects
  • Phenylbutyrates / chemistry*
  • Prostaglandin-Endoperoxide Synthases / metabolism
  • Rats
  • Stomach / drug effects
  • Stomach / pathology
  • Ulcer / chemically induced
  • Ulcer / pathology

Substances

  • Analgesics
  • Anti-Inflammatory Agents
  • Cyclooxygenase Inhibitors
  • Oxadiazoles
  • Phenylbutyrates
  • fenbufen
  • Prostaglandin-Endoperoxide Synthases