Abstract
To elucidate the active conformation of indometacin that differentiates between cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2), the stereochemistry around the N-benzoylated indole moiety of indometacin was studied. Resolution of stable atropisomers as representative conformations was found to be possible by restricting rotation about the N-C7' and/or C7'-C1' bond. Only the aR-isomer showed specific inhibition of COX-1, and COX-2 was not inhibited by either atropisomer.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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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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Cyclooxygenase 1 / metabolism
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Cyclooxygenase 2 / metabolism
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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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Drug Design
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Indomethacin* / analogs & derivatives
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Indomethacin* / chemical synthesis
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Indomethacin* / chemistry
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Indomethacin* / pharmacology
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Models, Molecular
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Stereoisomerism
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Structure-Activity Relationship
Substances
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Anti-Inflammatory Agents, Non-Steroidal
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Cyclooxygenase Inhibitors
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Cyclooxygenase 1
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Cyclooxygenase 2
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Indomethacin