Preparation and antiarthritic and analgesic activity of 4,5-diaryl-2-(substituted thio)-1H-imidazoles and their sulfoxides and sulfones.
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.
D000698:Analgesia; D000818:Animals; D000893:Anti-Inflammatory Agents; D001168:Arthritis / Q000188:drug therapy*; D001169:Arthritis, Experimental / Q000188:drug therapy*; D055598:Chemical Phenomena; D002621:Chemistry; D005260:Female; D007093:Imidazoles / Q000138:chemical synthesis / Q000627:therapeutic use*; D007213:Indomethacin / Q000627:therapeutic use; D008297:Male; D051379:Mice; D010653:Phenylbutazone / Q000627:therapeutic use; D051381:Rats; D011917:Rats, Inbred Lew; D013329:Structure-Activity Relationship; D013450:Sulfones; D013454:Sulfoxides; D005466:Fluorocarbons
D000893:Anti-Inflammatory Agents; D007093:Imidazoles; D007213:Indomethacin; D010653:Phenylbutazone; D013450:Sulfones; D013454:Sulfoxides; C041583:tiflamizole; D005466:Fluorocarbons