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

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·H2O). The anti-inflammatory properties of 3a·H2O 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.

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