Chemical and biological investigation of N-hydroxy-valdecoxib: An active metabolite of valdecoxib

• Published in: Bioorganic & medicinal chemistry Vol. 16; no. 9; pp. 5322 - 5330
• Main Authors: Erdélyi, Péter, Fodor, Tamás, Varga, Ágnes Kis, Czugler, Mátyás, Gere, Anikó, Fischer, János
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.05.2008; Elsevier Science
• Subjects: Active metabolite; Analgesics; Animals; Anti-Inflammatory Agents, Non-Steroidal - chemistry; Anti-Inflammatory Agents, Non-Steroidal - metabolism; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Biological and medical sciences; Bones, joints and connective tissue. Antiinflammatory agents; Carrageenan; Cattle; COX-2; Crystallography, X-Ray; Cyclooxygenase 1 - chemistry; Cyclooxygenase 2 - chemistry; Cyclooxygenase 2 - drug effects; Cyclooxygenase 2 Inhibitors - chemistry; Cyclooxygenase 2 Inhibitors - metabolism; Cyclooxygenase 2 Inhibitors - pharmacology; Cyclooxygenase-2 inhibitor; Disease Models, Animal; Dose-Response Relationship, Drug; Edema - chemically induced; Edema - drug therapy; Humans; Hyperalgesia - chemically induced; Hyperalgesia - drug therapy; Inflammation - drug therapy; Isoxazoles - chemistry; Isoxazoles - metabolism; Isoxazoles - pharmacology; Male; Medical sciences; Models, Molecular; Molecular Structure; Neuropharmacology; Non-steroidal anti-inflammatory drugs; Pain - drug therapy; Pain Measurement - methods; Pharmacology. Drug treatments; Rabbits; Rats; Rats, Wistar; Recombinant Proteins - drug effects; Stereoisomerism; Sulfonamides - chemistry; Sulfonamides - metabolism; Sulfonamides - pharmacology; Time Factors; Valdecoxib analogues; Cyclooxygenase-2 inhibitor; Active metabolite; COX-2; Valdecoxib analogues; Non-steroidal anti-inflammatory drugs; Prostaglandin-endoperoxide synthase; Isoxazole derivatives; Rat; Metabolite; Cyclooxygenase 2; Cyclooxygenase 2 inhibitor; Chemical synthesis; Edema; Sulfonamide; Enzyme; Rodentia; Oral administration; Enzyme inhibitor; Valdecoxib; In vitro; Biological activity; Non steroidal antiinflammatory agent; In vivo; Vertebrata; Mammalia; Analgesic; Mouse; Animal; Oxidoreductases
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2008.02.088

The inhibition of cyclooxygenase enzymes plays an important role in the treatment of inflammatory diseases. N-Hydroxy-4-(5-methyl-3-phenylisoxazol-4-yl)benzenesulfonamide ( 3)—a primary metabolite of the highly selective COX-2 inhibitor valdecoxib—was synthesized and stabilized as its monohydrate ( 3a·H 2O). The anti-inflammatory properties of 3a·H 2O were investigated in carrageenan-induced edema and in acute and chronic pain models. Based on our biological investigation, we conclude that N-hydroxy-valdecoxib 3a is an active metabolite of valdecoxib.