Abbott Laboratories Corporation

Joseph F Dellaria, Jr

Dee W Brooks

Anwer Basha

Linda J Chernesky

Lawrence A Black

Jimmie L Moore

Wendy Lee

Karen E Rodriques

Robert G Maki

James B Summers, Jr

James H Holms

Clint D Brooks

James D Ratajczyk

George W Carter

Todd H Gane

Kevin J Sallin

Linda J Dorn

Biswanath De

Saul H Rosenberg

Steven K Davidsen

Alan S Florjancic

Michael L Curtin

William R Baker

Yan Guo

Jianchun Gong

Yujia Dai

Howard Robin Heyman

Douglas H Steinman

Carol K Wada

Michael R Michaelides

Lianhong Xu

Jamie R Stacey

Thomas N Zydowsky

Hwan S Jae

Reverse hydroxamate inhibitors of matrix metalloproteinases

Urokinase inhibitors

The present invention provides a compound of the formula: ##STR1## Such compounds are useful for inhibiting prostaglandin synthesis. Pharmaceutical compositions and methods for inhibiting prostaglandin synthesis are also disclosed.

Prostaglandin synthase-2 inhibitors

The present invention provides a compound of the formula: ##STR1## such compounds are useful for inhibiting prostaglandin synthesis. Pharmaceutical compositions and methods for inhibiting prostaglandin synthesis are also disclosed.

Compounds of the structure ##STR1## where R.sup.1 is alkyl of one to four carbon atoms and R.sup.2 is selected from

Heteroatom substituted propanyl derivatives having 5-lipoxygenase

Arylamidoalkyl-N-hydroxyurea compounds having lipoxygenase inhibitory

Compounds of structure ##STR1## where W is selected from ##STR2## where Q is oxygen or sulfur, R.sup.5 and R.sup.6 are independently selected from hydrogen and alkyl, or R.sup.5 and R.sup.6, together with the nitrogen atoms to which they are attached, define a radical of formula ##STR3## L.sup.1 and L.sup.2 are independently selected from a valence bond, alkylene, propenylene, and propynylene, R.sup.1, R.sup.2, R.sup.3, and R.sup.4 are independently selected from alkyl, alkoxy, haloalkyl, halogen, cyano, amino, alkoxycarbonyl, and dialkylaminocarbonyl, Y is oxygen, &gt;NR.sup.9 where R.sup.9 is hydrogen or alkyl, or ##STR4## where n=0, 1, or 2, and A is selected from ##STR5## inhibit the biosynthesis of leukotrienes. These compounds are useful in the treatment or amelioration of allergic and inflammatory disease states.

Pyran-4-ylmethyl substituted arylalkylaryl-, arylalkenylylaryl-, and

Compounds of the structure ##STR1## where Ar.sup.1 is selected from optionally substituted carbocyclic aryl; optionally substituted 5- or 6-membered heterocyclic aryl; optionally substituted 10-membered bicyclic heterocyclic aryl containing one or two nitrogen atoms; optionally substituted benzo[b]furyl; optionally substituted benzo[b]thienyl; ##STR2## L.sup.1 is a valence bond, alkylene, propenylene, or propynylene; Y is oxygen, &gt;NR.sup.5, or &gt;S(O)n; Ar.sup.2 is optionally substituted phenyl; L.sup.2 is ##STR3## and R.sup.1 and R.sup.2 are alkyl, or taken together define a group of formula ##STR4## 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.

1, 2-dialkoxyethanes as 5-lipoxygenase inhibitors

Indole derivatives which inhibit leukotriene biosynthesis

Compounds of the structure ##STR1## where W is selected from ##STR2## where Q is oxygen or sulfur, R.sup.6 and R.sup.7 are hydrogen or alkyl, or R.sup.6 and R.sup.7, together with the nitrogen atoms to which they are attached, define a radical of formula ##STR3## Z is --CH.sub.2 --, oxygen, sulfur, or --NR.sup.9, L.sup.1 and L.sup.2 are selected from a valence bond, alkylene, propenylene, and propynylene; R.sup.1 and R.sup.2 are independently selected from alkyl, alkoxy, haloalkyl, halogen, cyano, amino, alkoxycarbonyl, and dialkylaminocarbonyl; Y is selected from oxygen, &gt;NR.sup.10, and ##STR4## L.sup.3 is selected from alkylene of one to three carbon atoms, propenylene, propynylene, ##STR5## and R.sup.3, R.sup.4, and R.sup.5 are hydrogen or alkyl of one to four carbon atoms inhibit the synthesis of leukotrienes. These compounds are useful in the treatment or amelioration of allergic and inflammatory disease states.

((4-alkoxypyran-4-yl) substituted) ether, arylalkyl-, arylalkenyl-, and

Compounds of formula ##STR1## Ar is optionally substituted phenyl, furyl, pyridyl, or thienyl; Y is selected from hydrogen, halogen, cyano, alkyl, haloalkyl, alkoxy, and alkoxycarbonyl; L is selected from ##STR2## and R.sup.1 and R.sup.2 are alkyl or together define a group of formula ##STR3## 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.

Polyether naphthalenic lignan lactones as inhibitors of 5-lipoxygenase

Compounds of the structure ##STR1## wherein W is selected from ##STR2## where Q is oxygen or sulfur, R.sup.6 and R.sup.7 are hydrogen or alkyl, or R.sup.6 and R.sup.7, together with the nitrogen atoms to which they are attached, define a radical of formula ##STR3## R.sup.8 is selected from hydrogen, alkyl, haloalkyl, optionally substituted phenyl, hydroxyalkyl, aminoalkyl, carboxyalkyl, (alkoxycarbonyl)alkyl, and (alkylaminocarbonyl)alkyl; Z is --CH.sub.2 --, oxygen, sulfur, or --NR.sup.9 where R.sup.9 is hydrogen or alkyl, L.sup.1 and L.sup.2 are selected from a valence bond, alkylene, propenylene, and propynylene, R.sup.1, R.sup.2, R.sup.3, and R.sup.4 are independently selected from alkyl, haloalkyl, halogen, cyano, amino, alkoxycarbonyl, and dialkylaminocarbonyl, Y is selected from oxygen, --NR.sup.10, where R.sup.10 is hydrogen or alkyl, and ##STR4## where n=0, 1, or 2, and R.sup.5 is alkyl, inhibit the biosynthesis of leukotrienes. These compounds are useful in the treatment or amelioration of allergic and inflammatory disease states.

(4-alkoxypyran-4-yl) substituted arylalkylaryl-, aryalkenylaryl-, and

Compounds of formula ##STR1## Ar is selected from (a) phenyl, (b) phenyl substituted with one or more groups selected from halogen, cyano, alkyl, haloalkyl, alkoxy, and alkoxycarbonyl, (c) furyl, (d) furyl substituted with one or more groups selected from halogen, alkyl, and alkoxy, (e) pyridyl, (f) pyridyl substituted with one or more groups selected from halogen, alkyl, and alkoxy, (g) thienyl, and (h) thienyl substituted with one or more groups selected from halogen, alkyl, and alkoxy; L is selected from alkylene of one to three carbon atoms, alkenylene of two to three carbon atoms, and alkynylene of two to three carbon atoms, and ##STR2## wherein p is an integer of 1 to 4, inclusive, and R.sup.4 is selected from the group consisting of hydrogen, alkyl of one to four carbon atoms, halogen, haloalkyl of one to four carbon atoms, and alkoxy of one to six carbon atoms; R.sup.1 is alkyl; R.sup.2 is hydrogen or alkyl; m is 1 or 2; Z is oxygen or CHOR.sup.3, and n is 0 or 1 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.

[Alkoxy-, alkenyloxy-, alkynyloxy-, and phenylmethyloxyalkoxycycloalkyl

Compounds of structure ##STR1## where W is selected from the group consisting of ##STR2## where Q is oxygen or sulfur, R.sup.7 and R.sup.8 are independently selected from hydrogen and alkyl, or R.sup.7 and R.sup.8, together with the nitrogen atoms to which they are attached, define a radical of formula ##STR3## L.sup.1 and L.sup.2 are independently selected from a valence bond, alkylene, propenylene, and propynylene; R.sup.1, R.sup.2, R.sup.3, and R.sup.4 are independently selected from alkyl, alkoxy, haloalkyl, halogen, cyano, amino, alkoxycarbonyl, and dialkylaminocarbonyl; Y is oxygen, &gt;NR.sup.11, where R.sup.11 is hydrogen or alkyl, or ##STR4## where n=0, 1, or 2; and R.sup.5 and R.sup.6 are alkyl, inhibit the biosynthesis of leukotrienes. These compounds are useful in the treatment or amelioration of allergic and inflammatory disease states.

(Trans-1,4-dialkoxycyclohexyl) substituted

Compounds of the structure ##STR1## where Ar is optionally substituted carbocyclic aryl, 5- or 6-membered heterocyclic aryl, 10-membered bicyclic heterocyclic aryl containing one or two nitrogen atoms, 9- or 10-membered heterocyclic containing one or two nitrogen atoms and optionally containing a further nitrogen or oxygen atom and one oxo or thioxo substituent, benzo[b]furyl, benzo[b]thienyl, A.sub.1 is propynylene, methylene, or a valence bond, X is O, S, SO.sub.2, or NR.sub.2, Y is selected from alkyl, haloalkyl, alkoxy, halogen, and hydrogen, A.sub.2 is selected from ##STR2## and methylene where Z is OR.sub.5 or NHR.sub.5 where R.sub.5 is hydrogen or alkyl, R.sub.1 is hydrogen, alkyl, or OR.sub.5, and m and n are integers having a value of 1 or 2 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.

Phenylmethyl derivatives having lipoxygenase inhibitory activity

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Lindenhurst, IL, United States of America

Joseph F Dellaria, Jr