Abbott Laboratories Corporation

Karen E Rodriques

Dee W Brooks

Joseph F Dellaria, Jr

Robert G Maki

James B Summers, Jr

Jimmie L Moore

George W Carter

Keith W Woods

James H Holms

Bruce W Horrom

Hormoz Mazdiyasni

Indole derivatives which inhibit leukotriene biosynthesis

Compounds of the structure ##STR1## where M is hydrogen, a pharmaceutically acceptable cation or metabolically cleavable group, R is alkyl, cycloalkyl, or NR.sup.1 R.sup.2, where R.sup.1 and R.sup.2 are hydrogen, alkyl, cycloalkyl alkonyl, or carbocyclic aryl, Y is alkylene, alkenylene, or cyclopropyl, and A is optionally substituted cycloalkyl or cycloalkylene are potent inhibitors of lipoxygenase enzymes and thus inhibit the biosynthesis of leukotrienes. These compounds are useful in the treatment or amelioration of allergic and inflammatory disease states.

Cycloalkyl N-hydroxy derivatives having lipoxygenase inhibitory activity

Compounds of the structure ##STR1## where A is straight or branched divalent alkylene or divalent cycloalkylene, R.sub.1 is selected from hydrogen; alkylthio; optionally substituted phenylthio; optionally substituted phenylalkylthio; optionally substituted 2-, 3-, and 4-pyridyl; optionally substituted 2-, and 3-thienylthio; and optionally substituted 2-thiazolythio, R.sub.2 is selected from --COOB; --COOalkyl; --COOalkyl(carbocyclic aryl); --CONR.sub.5 R.sub.6 ; --COR.sub.6 ; and --OH, R.sub.3 is selected from phenylalkyl and heteroarylalkyl, and R.sub.4 is selected from optionally substituted alkoxy(carbocyclic aryl); optionally substituted carbocyclic aryloxy; optionally substituted heteroarylalkoxy; and optionally substituted heteroaryloxy are potent inhibitors of lipoxygenase enzymes and thus inhibit the biosynthesis of of leukotrienes. These compounds are useful in the treatment or amelioration of allergic and inflammatory disease states.

Indole carboxylate derivatives which inhibit leukotriene biosynthesis

Compounds of the structure ##STR1## where M is a pharmaceutically acceptable cation or a metabolically cleavable group, R is alkyl, cycloalkyl or --NR.sup.1 R.sup.2, where R.sup.1 and R.sup.2 are hydrogen, alkyl, cycloalkyl or alkanoyl, and A is optionally substituted alkyl, cycloalkyl, carbocyclic aryl, benzo[b]furyl, thienyl, or benzo[b]thienyl are potent inhibitors of lipoxygenase enzymes and thus inhibit the biosynthesis of leukotrienes. These compounds are useful in the treatment or amelioration of allergic and inflammatory disease states.

Cyclobutyl derivatives having lipoxygenase inhibitory activity

Lipoxygenase inhibiting compounds

Certain carbocyclic aryl- and heterocyclic aryl- substituted cyclopropyl N-hydroxyureas, N-hydroxy-carboxamides, and N-acyl-N-hydroxyamines inhibit 5- and/or 12-lipoxygenase and are useful in the treatment of inflammatory disease states.

Cyclopropyl derivative lipoxygenase inhibitors

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 of the formula: ##STR1## wherein A is CH.sub.2 ; n is 0 or 1; R.sub.1 and R.sub.2 are independently selected from the group consisting of hydrogen, alkyl, alkenyl, aralkyl and cycloalkyl; Z is the residue from a non-steroidal anti-inflammatory carboxylic acid compound; and M is a pharmaceutically acceptable cation or a metabolically cleavable group; and the pharmaceutically acceptable salts thereof; and a non toxic pharmaceutically acceptable carrier. These compounds are useful as inhibitors of 5-lipoxygenase.

Certain carbocyclic aryl- and heterocyclic aryl-substituted cyclopropyl N-hydroxyureas, N-hydoroxycarboxamides, and N-acyl-N-hydroxyamides inhibit 5- and/or 12-lipoxygenase and are useful in the treatment of inflammatory disease states.

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

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Grayslake, IL, United States of America

Karen E Rodriques