Abstract
A series of 6,7-diaryl-2,3-1H-dihydropyrrolizines was prepared as COX-1/COX-2 and 5-LOX inhibitors. The inhibition of COX-1 was evaluated using intact bovine platelets as the enzyme source, whereas LPS-stimulated human monocytes served as the enzyme source for inducible COX-2. The determination of arachidonic metabolites was performed by HPLC for COX-1 and RIA for COX-2. The balance between COX-1/COX-2 and 5-LOX inhibition can be shifted by modifying the substitution pattern of the phenyl moiety at the 6- and 7-position of the pyrrolizine nucleus. Structure-activity relationships 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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Blood Platelets / enzymology
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Cattle
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Chromatography, High Pressure Liquid
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Cyclooxygenase 1
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Cyclooxygenase 2
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Drug Design
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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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Humans
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Isoenzymes / antagonists & inhibitors*
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Lipoxygenase Inhibitors*
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Membrane Proteins
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Monocytes / enzymology
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Prostaglandin-Endoperoxide Synthases
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Pyrroles / chemistry*
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Radioimmunoassay
Substances
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Enzyme Inhibitors
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Isoenzymes
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Lipoxygenase Inhibitors
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Membrane Proteins
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Pyrroles
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pyrroline
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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