Abbott Laboratories Corporation

Anwer Basha

Lawrence A Black

Andrew O Stewart

Dee W Brooks

Joseph F Dellaria, Jr

Pramila A Bhatia

Wendy Lee

Jianguo Ji

Michael R Schrimpf

Jerome F Daanen

Kevin B Sippy

William H Bunnelle

Karin Rosemarie Tietje

Clint D Brooks

Richard B Toupence

James D Ratajczyk

Linda J Chernesky

Teodozyj Kolasa

Meena V Patel

Michael E Kort

Huaqing Liu

Jeffrey J Rohde

Michael J Coghlan

Catherine M McCarty

Jennifer M Frost

Daniel Joseph Kerkman

Bruce P Gunn

Jonathan G Martin

Jennifer M Pace

Randy Bell

Richard A Craig

Richard Dennis Dyer

George W Carter

Linda J Dorn

Compounds of formula I pharmaceutical compositions of these compounds, and use of said compositions to control synaptic transmission in mammals.

Diazabicyclic central nervous system active agents

The present invention describes pyridazinone compounds of formula I which are cyclooxygenase (COX) inhibitors, and in particular, are selective inhibitors of cyclooxygenase-2 (COX-2), COX-2 is the inducible isoform associated with inflammation, as opposed to the constitutive isoform, cyclooxygenase-1 (COX-1) which is an important 'housekeeping' enzyme in many tissues, including the gastrointestinal (GI) tract and the kidneys. The selectivity of these compounds for COX-2 minimizes the unwanted GI and renal side-effects seen with currently markered non-steroidal anti-inflammatory drugs (NSAIDs).

Prostaglandin endoperoxide H synthase biosynthesis inhibitors

The present invention describes pyridazinone compounds of formula Iwhich are cyclooxygenase (COX) inhibitors, and in particular, are selective inhibitors of cyclooxygenase-2 (COX-2). COX-2 is the inducible isoform associated with inflammation, as opposed to the constitutive isoform, cyclooxygenase-1 (COX-1) which is an important 'housekeeping' enzyme in many tissues, including the gastrointestinal (GI) tract and the kidneys. The selectivity of these compounds for COX-2 minimizes the unwanted GI and renal side-effects seen with currently marketed non-steroidal anti-inflammatory drugs (NSAIDs).

The present invention describes pyridazinone compounds of formula I

Substituted arylalkynyl-and heteroarylalkynl-N-hydroxyurea inhibitors of

Compounds of the structure ##STR1## where p and q are zero or one, but cannot both be the same, M is a pharmaceutically acceptable cation or a metabolically cleavable group, B is a valence bond or a straight or branched alkylene 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 carbocyclic aryl, furyl, 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.

Furyl and thienyl alkynyl-N-hydroxy urea derivatives

Compounds having the structure ##STR1## or a pharmaceutically acceptable salt thereof have activity as inhibitors of cylooxygenase and 5-lipoxygenase, reduce the biosynthesis of leukotrienes B.sub.4, C.sub.4, D.sub.4, and E.sub.4 and cylooxygenase products such as prostaglandins and thromboxane and are useful in the treatment of inflammatory and allergic disease states. The compounds have the structure indicated above wherein A is selected from (a) optinally substituted carbocyclic aryl, (b) optinally substituted furyl, (c) optinally substituted benzo[b]furyl, (d) optinally substituted thienyl, (e) optinally substituted pyridyloxy, (f) optinally substituted pyridylalkyl, (g) optinally substituted benzo[b]thienyl, (h) optinally substituted pyridyl, (i) optinally substituted quinolyl, and (j) optinally substituted indolyl; X is selected from (a) optionally substituted alkyl, (b) optinally substituted alkenyl, and (c) optinally substituted alkynyl; R.sup.1 and R.sup.2 are independently selected from hydrogen, hydroxy, and alkyl; and Z is a residue of a non-steroidal anti-inflammatory drug of the general formula Z--COOH.

Lipoxygenase and cyclooxygenase inhibiting compounds

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

Acetylene derivatives having lipoxygenase inhibitory activity

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

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Anwer Basha