Abstract
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.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
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 / pharmacology*
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Binding, Competitive
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Carboxylic Acids / chemistry
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Cyclooxygenase 1
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Cyclooxygenase Inhibitors / chemistry
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Cyclooxygenase Inhibitors / pharmacology*
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Flurbiprofen / chemistry
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Flurbiprofen / metabolism
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Flurbiprofen / pharmacology
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Halogens / chemistry
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Ibuprofen / analogs & derivatives
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Ibuprofen / pharmacology
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Isoenzymes / antagonists & inhibitors*
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Kinetics
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Propionates / chemistry*
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Propionates / pharmacology*
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Prostaglandin-Endoperoxide Synthases
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Sheep
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Structure-Activity Relationship
Substances
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Anti-Inflammatory Agents, Non-Steroidal
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Carboxylic Acids
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Cyclooxygenase Inhibitors
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Halogens
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Isoenzymes
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Propionates
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Flurbiprofen
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Cyclooxygenase 1
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Prostaglandin-Endoperoxide Synthases
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propionic acid
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Ibuprofen