Abstract
Ketoprofenoyl-CoA thioester 3 was synthesized by coupling ketoprofen to coenzyme A using the mixed anhydride method. Diastereoisomeric compounds 3a and 3b corresponding to the enantiomers of ketoprofen, were obtained in optically pure form by preparative HPLC. A non-acylating analogue, rac-3-(3-benzoylphenyl)-2-oxo-butanoyl-CoA (7) was also prepared. The biological evaluation suggested that 3a and 3b are reversible inhibitors of COX-1 and irreversible inhibitors of COX-2. Compound 7 appears to be a poor but selective inhibitor of COX-1.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acyl Coenzyme A / chemistry*
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Acyl Coenzyme A / pharmacology
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Anhydrides / chemistry
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Animals
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Anti-Inflammatory Agents, Non-Steroidal / chemical synthesis*
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Anti-Inflammatory Agents, Non-Steroidal / chemistry
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Anti-Inflammatory Agents, Non-Steroidal / pharmacology
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Cell Line
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Cross-Linking Reagents / chemistry
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Cyclooxygenase 1
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Cyclooxygenase 2
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Cyclooxygenase 2 Inhibitors
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Cyclooxygenase Inhibitors / chemical synthesis*
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Cyclooxygenase Inhibitors / chemistry
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Cyclooxygenase Inhibitors / pharmacology
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Isoenzymes / antagonists & inhibitors*
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Ketoprofen / chemistry*
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Ketoprofen / pharmacology
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Prostaglandin-Endoperoxide Synthases
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Structure-Activity Relationship
Substances
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Acyl Coenzyme A
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Anhydrides
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Anti-Inflammatory Agents, Non-Steroidal
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Cross-Linking Reagents
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Cyclooxygenase 2 Inhibitors
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Cyclooxygenase Inhibitors
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Isoenzymes
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Ketoprofen
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Cyclooxygenase 1
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Cyclooxygenase 2
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Prostaglandin-Endoperoxide Synthases