Merck Frosst Canada, Inc.

Merck + Co., Inc.

Other

Merck Sharp + Dohme Corp.

M. S. & D. (i.a.) Corp.

Joshua Rokach

Clarence S Rooney

Yvan Guindon

Patrice C Belanger

Edward J Cragoe, Jr

Robert N Young

Christiane Yoakim

Rejean Fortin

Cheuk K Lau

Joseph G Atkinson

Yves Girard

Pierre A Hamel

John Scheigetz

Masatoshi Kakushima

John W Gillard

Haydn W Williams

Grant W Reader

Richard Frenette

Michel L Belley

Julian Adams

Edward C Hayes

Haydn R Williams

Michel Therien

Ralph F Hirschmann

Claude Dufresne

John Q Trojanowski

Garret A FitzGerald

Norman R Hunter

Brian Fitzsimmons, Deceased

Domenico Pratico

Maryann Fitzsimmons, Heir

John Schiegetz

The invention includes methods useful for the diagnosis of Alzheimer's disease and the evaluation of enhanced levels of lipid peroxidation in a mammal. The methods utilize isoprostanes as sensitive and stable molecular markers for lipid peroxidation in a mammal. Methods of identifying compounds useful for the treatment of Alzheimer's disease or for reducing levels of lipid peroxidation in a mammal are also included. The invention also includes kits useful for the diagnosis of Alzheimer's disease and for the evaluation of levels of lipid peroxidation in a mammal.

Methods and compositions for determining lipid peroxidation levels in oxidant stress syndromes and diseases

Compounds of the Formulae: ##STR1## are antagonists of leukotrienes of C.sub.4, D.sub.4 and E.sub.4, the slow reacting substance of anaphylaxis. These compounds are useful as anti-asthmatic, anti-allergic, anti-inflammatory, and cytoprotective agents.

Leukotriene antagonists

Compounds of the formula: ##STR1## where R.sup.2 contains certain aryls or heteroaryls are effective leukotriene inhibitors.

5-hydroxy-2,3-dihydrobenzofuran analogs as leukotriene biosynthesis

Benzofuran derivatives, pharmaceutical compositions and methods of treatment are disclosed. These compounds are useful as inhibitors of mammalian leukotriene biosynthesis. As such, these compounds are useful therapeutic agents for treating allergic conditions, asthma, cardiovascular disorders, inflammation. The compounds are also useful as analgesics and as cytoprotective agents.

Benzofuran derivatives

Compounds of the Formula I: ##STR1## and pharmaceutically acceptable salts thereof are leukotriene antagonists. These compounds inhibit SRS-A and leukotriene synthesis and are antagonists of SRS-A and are thus useful in the treatment of asthma, allergic disorders, inflammation, skin diseases and certain cardiovascular disorders.

Compounds having the formula: ##STR1## are antagonists of leukotrienes of C.sub.4, D.sub.4 and E.sub.4, the slow reaction substance of anaphylaxis. These compounds are useful as anti-asthmatic, anti-allergic, anti-inflammatory and cytoprotective agents.

4,7-Benzofurandione derivatives of Formula I, pharmaceutical compositions, and methods of treatment are disclosed. These compounds are useful as inhibitors of mammalian leukotriene biosynthesis. As such, these compounds are useful therapeutic agents for treating allergic conditions, asthma, cardiovascular disorders, inflammation, psoriasis and allergic conjunctivitis. The compounds are also useful as analgesics and as cytoprotective agents. Also disclosed are novel intermediates useful for the preparation of the 4,7-benzofurandiones of this invention. ##STR1##

4,7-benzofurandione derivatives

Leukotrienes may be conjugated with various proteins such as Bovine Serum Albumin (BSA) and Hemocyanin from Giant Keyhole Limpets (KLH) using 1,5-difluoro-2,4-dinitrobenzene or 6-N-maleimidohexanoic acid chloride as coupling agents. These conjugates are useful as reagents in a newly developed immunoassay for leukotrienes, as well as having potential utility as chemical immunotherapeutic agents in the treatment of various allergic and chronic inflammatory diseases of the skin, lung, and airways, including asthma, allergic rhinitis, rheumatoid arthritis, and skin diseases such as psoriasis and eczema.

Leukotriene by amides and hydrazides

Phenothiazone derivatives and analogs thereof, pharmaceutical compositions and methods of treatment are disclosed. These compounds are useful as inhibitors of mammalian leukotriene biosynthesis. As such, these compounds are useful therapeutic agents for treating allergic conditions, asthma, cardiovascular disorders and inflammation.

Phenothiazone derivatives and analogs

Pharmaceutical compositions containing a compound of Formula I: ##STR1## wherein X is O, S, SO or SO.sub.2 and R.sub.2, R.sub.3, R.sub.4 and R.sub.5 may be positioned anywhere on the structure, or a pharmaceutically-acceptable salt thereof and certain novel benzo[a]phenothiazines, which compositions and compounds are useful in treating allergic conditions, asthma, cardiovascular disorders, inflammation and pain and are useful as cytoprotective agents.

Benzo[a]phenothiazines and hydro-derivatives for inhibiting leukotriene

Compounds having the formula: ##STR1## are antagonists of leukotrienes of C.sub.4, D.sub.4, E.sub.4 and the slow reacting substance of anaphylaxis. As such, these compounds will be useful as anti-asthmatic, anti-allergic, anti-inflammatory and cytoprotective agents.

Benzofuran derivatives, pharmaceutical compositions and methods of treatment are disclosed. These compounds are useful as inhibitors of mammalian leukotriene biosynthesis. As such, these compounds are useful therapeutic agents for treating allergic conditions, asthma, cardiovascular disorders, inflammation. The compounds ar also useful as analgesics and as cytoprotective agents.

Benzofuran derivatives useful as inhibitors of mammalian leukotriene

Pharmaceutical compositions of phenothiazone derivatives and analogs

Compounds having the formula: ##STR1## are antagonists of leukotrines of C.sub.4, D.sub.4 and E.sub.4, the slow reacting substance of anaphylaxis. These compounds are useful as anti-asthmatic, anti-allergic and anti-inflammatory agents.

Certain pyridyl derivatives useful as leukotriene antagonists

Phenothiazine derivatives and analogs thereof having the Formula I are useful as inhibitors of the biosynthesis of mammalian leukotrienes. As such, these compounds are useful therapeutic agents for treating allergic conditions, asthma, cardiovascular disorders and inflammation, and are useful as cytoprotective agents. ##STR1##

Growing community of inventors

Laval, Canada

Joshua Rokach