Indole iminooxy derivatives which inhibit leukotriene biosynthesis

摘要

Compounds of the structure where A1 is alkylene or cycloalkylene; A2 is a valence bond, alkylene, or cycloalkylene; R1 is selected from hydrogen, alkylthio, optionally substituted phenylthio, optionally substituted phenylalkylthio, optionally substituted 2-, 3- and 4-pyridylthio, optionally substituted 2- and 3-thienylthio, and optionally substituted 2-thiazolylthio; R2 is selected from optionally substituted phenylalkyl and optionally substituted heteroarylakyl; R3 is selected from alkyl, alkoxy, optionally substituted phenyl, optionally substituted phenoxy, optionally substituted phenylalkyl, optionally substituted phenylalkoxy, optionally substituted naphthyl,optionally substituted naphthyloxy, optionally substituted naphthylalkyl, optionally substituted naphthylalkoxy, optionally substituted heteroaryl, optionally substituted heteroaryloxy, optionally substituted heteroarylalkyl, and optionally substituted heteroarylalkoxy; R4 is selected from hydrogen and optionally substituted alkyl; and Z is selected from -COOB, -C(OB)R6R6, -COOalkyl, -COOalkylaryl, -CONR5R6, and -COR6 are potent inhibitors of lipoxygenase enzymes and thus inhibit the biosynthesis of leukotrienes. These compounds are useful in the treatment of amelioration of allergic and inflammatory disease states.