Abstract
Novel substituted 2-methyl-3-indolylacetic derivatives were synthesized and evaluated for their activity in vitro and in vivo on COX-1 and COX-2. Active compounds were screened to determine their gastrointestinal tolerability in vivo in the rat. Results showed that 3 and 4 preferentially inhibited COX-1 in vitro and in vivo. MD simulations indicated an induced fit for COX-1 but not for COX-2, probably because of a lower plasticity of the latter.
MeSH terms
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Acute Disease
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Animals
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Anti-Inflammatory Agents / chemical synthesis*
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Anti-Inflammatory Agents / chemistry
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Anti-Inflammatory Agents / pharmacology*
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Cyclooxygenase 1 / chemistry*
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Cyclooxygenase 1 / metabolism
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Cyclooxygenase 2 / chemistry*
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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 Evaluation, Preclinical
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Edema / chemically induced
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Edema / drug therapy
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Indoleacetic Acids / chemical synthesis*
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Indoleacetic Acids / chemistry
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Indoleacetic Acids / pharmacology*
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Membrane Proteins / chemistry*
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Membrane Proteins / metabolism
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Models, Molecular
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Rats
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Stomach / drug effects*
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Stomach / pathology
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Structure-Activity Relationship
Substances
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Anti-Inflammatory Agents
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Cyclooxygenase Inhibitors
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Indoleacetic Acids
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Membrane Proteins
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Cyclooxygenase 1
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Cyclooxygenase 2
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PTGS2 protein, human