Synthesis of indolylalkoxyiminoalkylcarboxylates as leukotriene biosynthesis inhibitors

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...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry 1997-03, Vol.5 (3), p.507-514
Main Authors: Kolasa, Teodozyj, Bhatia, Pramila, Brooks, Clint D.W., Hulkower, Keren I., Bouska, Jennifer B., Harris, Richard R., Bell, Randy L.
Format: Article
Language:English
Subjects:
5-Lipoxygenase-Activating Proteins
Animals
Carrier Proteins - metabolism
Indoles - chemical synthesis
Indoles - chemistry
Indoles - pharmacology
Isomerism
Leukotriene Antagonists
Leukotrienes - biosynthesis
Lipoxygenase Inhibitors - chemical synthesis
Lipoxygenase Inhibitors - chemistry
Lipoxygenase Inhibitors - pharmacology
Magnetic Resonance Spectroscopy
Membrane Proteins - metabolism
Models, Chemical
Quinolines - chemical synthesis
Quinolines - chemistry
Quinolines - pharmacology
Rats
Structure-Activity Relationship
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Summary: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 IC 50s of 21 and 9 nM and in vivo leukotriene inhibition in the rat with oral ED 50s of 0.9 and 1.7 mg/kg, respectively. A series of quinolylmethoxyindolylalkyliminoxycarboxylates were synthesized and evaluated for inhibition of leukotriene biosynthesis.
ISSN:0968-0896
1464-3391
DOI:10.1016/S0968-0896(96)00265-9