Abbott Laboratories Corporation

James D Ratajczyk

Anwer Basha

Clint D Brooks

Andrew O Stewart

Fortuna Haviv

Pramila A Bhatia

Joseph F Dellaria, Jr

Dee W Brooks

Yi-Yin Ku

Christopher Bieniarz

Sanjay R Chemburkar

Daniel A Dickman

Robert George Stein

Richard A Craig

Juliette K Busse

Harry O Spiwek

Bhadra Shelat

Mazhar Husain

Hemantkumar H Patel

David P Sawick

Leo Ralph Swett

Ramesh R Patel

John N Starr

Mark Bures

Dominique Bridon

Francis E Fischer

Substituted arylalkynyl-and heteroarylalkynl-N-hydroxyurea inhibitors of

A process for preparing a compound of the structure I ##STR1## where A is oxygen and sulfur and R.sup.1 is selected from the group consisting of hydrogen, halogen, alkyl of one to six carbon atoms, alkoxy of one to six carbon atoms, and trifluoromethyl, and R.sup.2 is alkyl of one to four carbon atoms, comprising coupling a compound of formula II: ##STR2## where X is bromine or iodine, with an N-hydroxyurea compound of formula III: ##STR3## in the presence of a palladium catalyst followed by reaction of the product thus formed with an alkali metal isocyante. The compounds of formula I are inhibitors of the enzyme 5-lipoxygenase and are thus useful as therapeutic agents for the treatment of allergic and inflammatory disease conditions.

Process for the preparation of N-4-[(substituted phenyl)alkylheterocyclic]-

The present invention discloses novel compounds useful as alkaline phosphatase inhibitors and therapeutic agents. Preferably, the novel compounds are useful as selective inhibitors of human alkaline phosphatases as opposed to Escherichia coli alkaline phosphatases. The novel compounds can also be used as cancer therapeutic agents, anti-depressive agents, anti-anergic agents, and antihelminthic agents. The novel compounds have the following general formula: ##STR1## wherein R' is an aryl, aryl ether, aryl thioether, aromatic heterocyclic, aromatic heterocyclic thioether, or aromatic heterocyclic ether group. More preferably, R' is a phenyl or a pyridine. Most preferably, R' is of the following formula: ##STR2## 2-thiopyridine, or ##STR3## 2-oxypyridine. R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.1 ', R.sub.2 ', R.sub.3 ', R.sub.4 ', and R.sub.5 ' can be the same or different, and at least one of which is selected from the group consisting of: H, C.sub.1 -C.sub.6 alkyl, halo C.sub.1 -C.sub.6 alkyl, phenyl, C.sub.1 -C.sub.6 alkoxy, phenoxy, trifluoromethyl, nitro, amino, carboxy, and halo groups with the proviso that each novel compound has no more than three substituents. Hydrogen is not considered a substituent.

Compounds useful as alkaline phosphatase inhibitors and therapeutic

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 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

The present invention relates to compounds of the formula ##STR1## and the pharmaceutically acceptable salts thereof wherein Z is selected from optionally substituted phenyl, furyl, thienyl or thiazolyl; which inhibits leukotriene biosynthesis and is useful in the treatment of inflammatory disease states; also disclosed are leukotriene biosynthesis inhibiting compositions and a method for inhibiting 5-lipoxygenase activity and leukotriene biosynthesis.

[(Substituted) phenyalkyl]furylalkynyl-and [substituted) phenyalkyl]

Described are compounds of the formula ##STR1## wherein R is hydrogen or loweralkyl, X, Y and W independently of one another denote hydrogen, halogen, loweralkyl, nitro, amino, amido, loweralkoxy, hydroxy, nitrile, methylsulfone, methylsulfoxide, methylmercapto, or trifluoromethyl; Z is oxygen, sulfur or --CH.sub.2 ; n and m are each an integer from 0 to 6 inclusive, or pharmaceutically acceptable salts thereof. The compounds are effective as anti-inflammatory agents.

[1-(2-Benzoxazolyl)hydrazino]alkyl nitrile derivatives

Novel 1,3-dimethyl-1H-pyrazolo[4,3-d]pyrimidine-7(6H)-ones. The compounds exhibit central nervous system activity, particularly anti-convulsant and sedative activity, and also exhibit anti-inflammatory activity and gastric antisecretory activity.

1,3-Dimethyl- 1H-pyrazolo(4,3-D) pyrimidine-7 (6H)-ones

Growing community of inventors

Waukegan, IL, United States of America

James D Ratajczyk