Abbott Laboratories Corporation

Robert G Maki

Dee W Brooks

Joseph F Dellaria, Jr

Karen E Rodriques

George W Carter

Andrew O Stewart

James B Summers, Jr

Jimmie L Moore

James H Holms

Indole derivatives which inhibit leukotriene biosynthesis

The present invention provides certain substituted oxime ether compounds which inhibit lipoxygenase enzyme activity and are useful in the treatment of allergic and inflammatory disease states. The compounds of this invention have the structure ##STR1## where M is hydrogen, a pharmaceutically acceptable cation, or a pharmaceutically acceptable metabolically cleavable group; p and q are independently zero or one, with the provisos that (i) p and q may not both be the same; (ii) when p is one and q is zero, R is selected from the group consisting of hydrogen, straight or branched alkyl of from one to twelve carbon atoms, and cycloalkyl of from three to eight carbon atoms; and (iii) when p is zero and q is one, R is selected from the group consisting of hydrogen, alkyl of from one to twelve carbon atoms, cycloalkyl of from three to eight carbon atoms, and --NR.sub.1 R.sub.2. L.sub.1 is a direct bond or is selected from the group consisting of alkyl of from one to six carbon atoms, alkylenyl, of from one to six carbon atoms, and alkynyl of from two to six carbon atoms; L.sub.2 is a direct bond or is alkyl of from one to six carbon atoms; Z is selected from the group consisting of hydrogen, alkyl of from one to six carbon atoms, and halosubstituted alkyl of from one to six carbon atoms; and A is optionally substituted carbocyclic or heterocyclic aryl, arylalkyl, or aryloxy.

Oxime ether derivatives having lipoxygenase inhibitory activity

Substituted indolyl compounds of the formula ##STR1## are potent inhibitors of the lipoxygenase enzymes and are useful as agents for the treatment of allergies and inflammatory disease states.

Compounds, compositions a method of inhibiting lipoxygenase and treating related disorders are disclosed. The compounds are of the formula:

Heteroaryl N-hydroxy amides and ureas with polar substituents as

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Kenosha, WI, United States of America

Robert G Maki