Abstract
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(2)O). The anti-inflammatory properties of 3a.H(2)O 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.
MeSH terms
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Animals
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Anti-Inflammatory Agents, Non-Steroidal / chemistry
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Anti-Inflammatory Agents, Non-Steroidal / metabolism*
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Anti-Inflammatory Agents, Non-Steroidal / pharmacology
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Carrageenan
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Cattle
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Crystallography, X-Ray
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Cyclooxygenase 1 / chemistry
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Cyclooxygenase 2 / chemistry
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Cyclooxygenase 2 / drug effects
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Cyclooxygenase 2 Inhibitors / chemistry
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Cyclooxygenase 2 Inhibitors / metabolism*
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Cyclooxygenase 2 Inhibitors / pharmacology
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Disease Models, Animal
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Dose-Response Relationship, Drug
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Edema / chemically induced
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Edema / drug therapy
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Humans
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Hyperalgesia / chemically induced
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Hyperalgesia / drug therapy
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Inflammation / drug therapy
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Isoxazoles / chemistry
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Isoxazoles / metabolism*
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Isoxazoles / pharmacology
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Male
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Models, Molecular
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Molecular Structure
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Pain / drug therapy
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Pain Measurement / methods
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Rabbits
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Rats
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Rats, Wistar
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Recombinant Proteins / drug effects
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Stereoisomerism
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Sulfonamides / chemistry
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Sulfonamides / metabolism*
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Sulfonamides / pharmacology
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Time Factors
Substances
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Anti-Inflammatory Agents, Non-Steroidal
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Cyclooxygenase 2 Inhibitors
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Isoxazoles
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N-hydroxy-valdecoxib
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Recombinant Proteins
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Sulfonamides
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valdecoxib
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Carrageenan
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Cyclooxygenase 1
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Cyclooxygenase 2