4-Hydroxy-3-quinolinecarboxamides with antiarthritic and analgesic activities.
A series of 4-hydroxy-3-quinolinecarboxamides has been synthesized and evaluated by the oral route as antiinflammatory agents in carrageenin-induced foot edema and adjuvant-induced arthritis and as analgesic agents in the acetic acid induced writhing test. Among the most active molecules, some have shown both analgesic and acute antiinflammatory activities. Others, such as compounds 24, 37, and 52, were only powerful peripherally acting analgesics. Compound 52, being active at 1 mg/kg (ED50), is the most potent compound in the series. Some analogues, substituted in the 2-position by an alcohol, ester, or amine function, displayed potent antiarthritic activity in the same range as that of piroxicam and were also active in acute tests of inflammation and nociception. They inhibited the activity of both cyclooxygenase and 5-lipoxygenase at micromolar concentrations. Compound 102 (RU 43526) showed potent antiarthritic activity (adjuvant-induced arthritis, ED50 = 0.7 mg/kg, po) and gastrointestinal tolerance (ED100 greater than 250 mg/kg, po) and thus it is presently undergoing an extensive pharmacological evaluation.
D000577:Amides / Q000138:chemical synthesis / Q000627:therapeutic use; D000698:Analgesia; D000818:Animals; D000893:Anti-Inflammatory Agents; D001168:Arthritis / Q000188:drug therapy*; D001169:Arthritis, Experimental / Q000188:drug therapy*; D002351:Carrageenan; D002417:Cattle; D055598:Chemical Phenomena; D002621:Chemistry; D016861:Cyclooxygenase Inhibitors; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D005260:Female; D006912:Hydroxyquinolines / Q000138:chemical synthesis / Q000627:therapeutic use*; D016859:Lipoxygenase Inhibitors; D008297:Male; D051379:Mice; D010147:Pain Measurement; D051381:Rats; D011917:Rats, Inbred Lew; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship
D000577:Amides; D000893:Anti-Inflammatory Agents; D016861:Cyclooxygenase Inhibitors; D006912:Hydroxyquinolines; D016859:Lipoxygenase Inhibitors; D002351:Carrageenan