Preparation and antiarthritic and analgesic activity of 4,5-diaryl-2-(substituted thio)-1H-imidazoles and their sulfoxides and sulfones

J Med Chem. 1985 Sep;28(9):1188-94. doi: 10.1021/jm00147a011.

Abstract

A series of 4,5-diaryl-2-(substituted thio)-1H-imidazoles was synthesized and evaluated as antiinflammatory and analgesic agents in the rat adjuvant induced arthritis assay and the mouse phenyl-p-benzoquinone writhing (PQW) assay. Several analogues were found to be more potent than phenylbutazone and indomethacin. Structure-activity relationships are discussed. One of the compounds, 4,5-bis(4-fluorophenyl)-2-[(1,1,2,2-tetrafluoroethyl)-sulfonyl]-1H- imidazole (8d, tiflamizole), was found to be 8 times as potent as indomethacin in the rat adjuvant induced arthritis assay and is presently undergoing clinical trial as an antiarthritic drug.

Publication types

  • Comparative Study

MeSH terms

  • Analgesia*
  • Animals
  • Anti-Inflammatory Agents
  • Arthritis / drug therapy*
  • Arthritis, Experimental / drug therapy*
  • Chemical Phenomena
  • Chemistry
  • Female
  • Imidazoles / chemical synthesis
  • Imidazoles / therapeutic use*
  • Indomethacin / therapeutic use
  • Male
  • Mice
  • Phenylbutazone / therapeutic use
  • Rats
  • Rats, Inbred Lew
  • Structure-Activity Relationship
  • Sulfones*
  • Sulfoxides*

Substances

  • Anti-Inflammatory Agents
  • Imidazoles
  • Sulfones
  • Sulfoxides
  • Phenylbutazone
  • tiflamizole
  • Indomethacin