Abstract
A series of substituted indolylalkoxyiminoalkylcarboxylates were found to be potent leukotriene biosynthesis inhibitors. The structure-activity relationships were investigated. Representative potent inhibitors identified were the quinolyl 3a (A-86885) and pyridyl 3b (A-86886) congeners with in vitro IC50s of 21 and 9 nM and in vivo leukotriene inhibition in the rat with oral ED50s of 0.9 and 1.7 mg/kg, respectively.
MeSH terms
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5-Lipoxygenase-Activating Proteins
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Animals
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Carrier Proteins / metabolism
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Indoles / chemical synthesis
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Indoles / chemistry*
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Indoles / pharmacology
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Isomerism
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Leukotriene Antagonists
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Leukotrienes / biosynthesis*
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Lipoxygenase Inhibitors / chemical synthesis
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Lipoxygenase Inhibitors / chemistry*
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Lipoxygenase Inhibitors / pharmacology
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Magnetic Resonance Spectroscopy
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Membrane Proteins / metabolism
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Models, Chemical
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Quinolines / chemical synthesis
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Quinolines / chemistry*
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Quinolines / pharmacology
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Rats
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Structure-Activity Relationship
Substances
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5-Lipoxygenase-Activating Proteins
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Alox5ap protein, rat
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Carrier Proteins
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Indoles
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Leukotriene Antagonists
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Leukotrienes
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Lipoxygenase Inhibitors
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Membrane Proteins
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Quinolines
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MK 0591