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 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.
Kolasa
T
T
Abbott Laboratories, Abbott Park, IL 60064-3500, USA.
Bhatia
P
P
Brooks
C D
CD
Hulkower
K I
KI
Bouska
J B
JB
Harris
R R
RR
Bell
R L
RL
D058927:5-Lipoxygenase-Activating Proteins; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D007536:Isomerism; D020024:Leukotriene Antagonists; D015289:Leukotrienes / Q000096:biosynthesis*; D016859:Lipoxygenase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D008565:Membrane Proteins / Q000378:metabolism; D008956:Models, Chemical; D011804:Quinolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship
D058927:5-Lipoxygenase-Activating Proteins; C548594:Alox5ap protein, rat; D002352:Carrier Proteins; D007211:Indoles; D020024:Leukotriene Antagonists; D015289:Leukotrienes; D016859:Lipoxygenase Inhibitors; D008565:Membrane Proteins; D011804:Quinolines; C078266:MK 0591