Abstract
Following our previous research on anti-inflammatory drugs (NSAIDs), we report here the synthesis of chiral 1,5-diarylpyrroles derivatives that were characterized for their in vitro inhibitory effects toward cyclooxygenase (COX) isozymes. Analysis of enzymatic affinity and COX-2 selectivity led us to the selection of one compound (+/-)-10b that was further tested in vitro in the human whole blood (HWB) and in vivo for its anti-inflammatory activity in mice. The affinity data have been rationalized through docking simulations.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetic Acid
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Alcohols / chemistry*
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Analgesics / chemical synthesis
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Analgesics / chemistry
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Analgesics / pharmacology*
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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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Binding Sites
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Carrageenan
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Cells, Cultured
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Computer Simulation
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Cyclooxygenase 1 / drug effects
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Cyclooxygenase 2 / drug effects
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Dose-Response Relationship, Drug
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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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Enzyme Activation / drug effects
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Enzyme Inhibitors / chemical synthesis
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacology
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Ethers / chemistry*
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Humans
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Isoenzymes / drug effects
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Male
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Mice
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Models, Chemical*
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Molecular Structure
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Pain / chemically induced
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Pain / drug therapy
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Pain Measurement / drug effects
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Pyrroles / chemical synthesis
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Pyrroles / chemistry
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Pyrroles / pharmacology*
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Rats
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Rats, Sprague-Dawley
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Rats, Wistar
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Stereoisomerism
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Structure-Activity Relationship
Substances
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Alcohols
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Analgesics
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Anti-Inflammatory Agents, Non-Steroidal
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Enzyme Inhibitors
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Ethers
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Isoenzymes
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Pyrroles
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Carrageenan
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Cyclooxygenase 1
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Cyclooxygenase 2
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Acetic Acid