Isoxicam and related 4-hydroxy-N-isoxazolyl-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxides. Potent nonsteroidal antiinflammatory agents.
A novel series of antiinflammatory agents, N-isoxazolyl-3-carboxamides of 4-hydroxy-2H-1,2-benzothiazine 1,1-dioxide, was synthesized and evaluated as antiinflammatory agents in the carrageenin-induced rat paw edema (CIRPE) assay and adjuvant-induced polyarthritis (AIP) assay. Several analogues were found to be equipotent or more potent than aspirin and phenylbutazone. Structure-activity relationships are discussed. One of the compounds, 4-hydroxy-2-methyl-N-(5-methyl-3-isoxazolyl)-2H-1,2-benzothiazine 3-carboxamide 1,1-dioxide (3a; isoxicam), was found to be 3 times as potent as phenylbutazone in the CIRPE and in the therapeutic AIP assays. Isoxicam (3a) is presently undergoing phase III clinical trial as an antiarthritic drug.
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D007555:Isoxazoles / Q000138:chemical synthesis / Q000494:pharmacology*; D008297:Male; D010080:Oxazoles / Q000494:pharmacology*; D010894:Piroxicam / Q000031:analogs & derivatives*; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship; D013843:Thiazines / Q000138:chemical synthesis / Q000494:pharmacology*
D000893:Anti-Inflammatory Agents; D007555:Isoxazoles; D010080:Oxazoles; D013843:Thiazines; D010894:Piroxicam; C013580:isoxicam