Janssen Pharmaceutica Nv

The United States of America, As Represented by the Secretary, Department of Health and Human Services

Other

University of California

Thomas Jefferson University

Eastern Virginia Medical School

The United States of America As Represented by the Department of Health

University of Delaware

Elias Set Jenö Arnér

Diane K Luci

William Alvin Kinney

Anton Simeonov

David Joseph Maloney

Ajit Jadhav

Edward Charles Lawson

Bruce E Maryanoff

Shyamali Ghosh

Thomas S Dexheimer

David A Taylor-Fishwick

Michael Holinstat

Theodore Holman

Adam Yasgar

Steven McKenzie

Nathan Patrick Coussens

William Chester Stafford

Jerry L Nadler

David F McComsey

Francois M Sommen

Sergey Sviridov

Zhihao Zhuang

Andrew S Rosenthal

Nikolay Marchenko

Ghosh Shyamali

Qin Liang

Steven E Mckenzie

Bruce E Maryonoff

Human lipoxygenases (LOXs) are a family of iron-containing enzymes involved in catalyzing the oxidation of polyunsaturated fatty acids to provide the corresponding bioactive hydroxyeicosatetraenoic acid (HETE) metabolites. These eicosanoid signaling molecules are involved in a number of physiologic responses such as platelet aggregation, inflammation, and cell proliferation. Platelet-type 12-(S)-LOX (12-LOX) is of particular interest because of its demonstrated role in skin diseases, diabetes, platelet hemostasis, thrombosis, and cancer. Disclosed herein is the identification and medicinal chemistry optimization of a 4-((2-hydroxy-3-methoxybenzyl)amino)benzenesulfonamide-based scaffold. The compounds display nM potency against 12-LOX and excellent selectivity over related lipoxygenases and cyclooxygenases. In addition to possessing favorable ADME properties, the compounds also inhibit PAR-4 induced aggregation and calcium mobilization in human platelets, and reduce 12-HETE in mouse/human beta cells. The compounds can also be used in methods for treating or preventing a 12-lipoxygenase mediated disease or disorder.

4-((2-hydroxy-3-methoxybenzyl)amino)benzenesulfonamide derivatives as potent and selective inhibitors of 12-lipoxygenase

There is provided compounds of formula (I) or pharmaceutically-acceptable salts thereof, wherein W, X, Y, Z, R, Rand Rhave meanings provided in the description, which compounds are useful in the treatment of cancers. 

Pyridazinones and their use in the treatment of cancer

There is provided compounds of formula (I) or pharmaceutically-acceptable salts thereof, wherein L, R, R, R, Rand n have meanings provided in the description, which compounds are useful in the treatment of cancers. 

Pyridines and their use in the treatment of cancer

There is provided compounds of formula (I), or pharmaceutically-acceptable salts thereof, wherein X, Y, Z, Rand Rhave meanings provided in the description, which compounds are useful in the treatment of cancers. 

Tricyclic compounds and their use in the treatment of cancer

Disclosed are inhibitors of the USP1/UAF1 deubiquitinase complex, for example. of formula (I), wherein R, R, and Q are as defined herein, which are useful in treating diseases such as cancer, and improving the efficacy of DNA damaging agents in cancer treatment. Also disclosed is a composition comprising a pharmaceutically suitable carrier and at least one compound of the invention, a method of method of inhibiting a heterodimeric deubiquitinase complex in a cell, and a method of enhancing the chemotherapeutic treatment of cancer in a mammal undergoing treatment with an anti cancer agent. Further disclosed is a method of preparing compounds of the invention.

Inhibitors of the USP1/UAF1 deubiquitinase complex and uses thereof

The present invention is directed to compounds of formula (I) 

Urotensin II receptor antagonists

The invention is directed to benzo[1,4]oxazin-3-one, benzo[1,4]thiazin-3-one and quinolin-2-one Urotensin II receptor antagonists useful in treating or ameliorating a Urotensin-II mediated disorder. More specifically, the present invention relates to certain novel benzo[1,4]oxazin-3-one, benzo[1,4]thiazin-3-one and quinolin-2-one compounds and methods for preparing compounds, compositions, intermediates and derivatives thereof. Pharmaceutical compositions and methods for treating or ameliorating a Urotensin-II mediated disorder using compounds of the invention are also described.

Benzo[1,4]oxazin-3-one, benzo[1,4]thiazin-3-one and quinolin-2-one urotensin II receptor antagonists

The invention is directed to Urotensin II antagonists. More specifically, the present invention relates to certain novel compounds, methods for preparing compounds, compositions, intermediates and derivatives thereof and methods for treating Urotensin-II mediated disorders. Pharmaceutical and veterinary compositions and methods of treating cardiovascular disorders and various other disease states or conditions using compounds of the invention are also described.

This invention is directed to a compound of Formula (I): and forms thereof, wherein A, B, E, G, X and Lare as defined herein and their use as urotensin II receptor antagonists.

The present invention is directed to substituted indanyl compounds of Formula (I): Useful for treating integrin-mediated disorders such as, but not limited to unstable angina, thromboemboic disorders, osteoporosis, growth and metastasis of malignant tumors, diabetic retinopathy, arthritis, viral disease and surgical adhesions.

Tricyclic indanyls as integrin inhibitors

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Horsham, PA, United States of America

Diane K Luci