Manipulation of kinetic profiles in 2-aryl propionic acid cyclooxygenase inhibitors.
The nonsteroidal anti-inflammatory drugs flurbiprofen and ibuprofen were modified in an attempt to alter the kinetics of inhibitor binding by COX-1. Contrary to prior predictions, a halogen substituent is not sufficient to confer slow tight-binding behavior. Conversion of the carboxylate moiety of flurbiprofen to an ester or amide abolishes slow tight-binding behavior, regardless of halogenation state.
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GENE-N CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL CHEMICAL GENE-Y
cyclooxygenase halogen carboxylate flurbiprofen ester amide flurbiprofen ibuprofen 2-aryl propionic acid COX-1