Abstract
Aroyl- and thiophene-substituted pyrrole derivatives have been synthesized as a new class of COX-1/COX-2 inhibitors. The inhibition of COX-1 was evaluated in a biological system using bovine PMNLs as the enzyme source, whereas LPS-stimulated human monocytes served as the enzyme source for inducible COX-2. The determination of the concentration of arachidonic acid metabolites was performed by HPLC for COX-1 and RIA for COX-2. Variation of the substitution pattern led to a series of active compounds which showed inhibition for COX-1 and COX-2. Structural requirements for the development of COX-1/COX-2 inhibitors are discussed.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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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 / pharmacology
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Arachidonic Acid / metabolism
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Cattle
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Cyclooxygenase 1
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Cyclooxygenase 2
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Cyclooxygenase 2 Inhibitors
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Cyclooxygenase Inhibitors / chemical synthesis*
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Cyclooxygenase Inhibitors / pharmacology
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Diclofenac / pharmacology
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Humans
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Indomethacin / pharmacology
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Isoenzymes / antagonists & inhibitors
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Isoenzymes / pharmacology
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Leukocytes, Mononuclear / drug effects
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Leukocytes, Mononuclear / enzymology
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Membrane Proteins
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Molecular Structure
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Monocytes / enzymology
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Neutrophils / drug effects
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Neutrophils / enzymology
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Prostaglandin-Endoperoxide Synthases / pharmacology
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Pyrroles / chemical synthesis*
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Pyrroles / pharmacology
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Sulfones / pharmacology
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Thiophenes / chemical synthesis
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Thiophenes / pharmacology
Substances
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Anti-Inflammatory Agents, Non-Steroidal
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Cyclooxygenase 2 Inhibitors
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Cyclooxygenase Inhibitors
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Isoenzymes
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Membrane Proteins
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Pyrroles
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SC 57666
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Sulfones
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Thiophenes
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Diclofenac
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Arachidonic Acid
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Cyclooxygenase 1
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Cyclooxygenase 2
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PTGS1 protein, human
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PTGS2 protein, human
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Prostaglandin-Endoperoxide Synthases
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Indomethacin