Rigel Pharmaceuticals, Incorporated

Curasen Therapeutics, Inc.

Bristol-myers Squibb Compnay

Other

Eli Lilly and Company

Bristol Meyers Squibb Company

Rigl Pharmaceutical, Inc.

Jiaxin Yu

Rajinder Paul Singh

Ihab S Darwish

Pingyu Ding

Sacha Holland

Hui Hong

Somasekhar Bhamidipati

Dane A Goff

Jing Zhang

Thilo J Heckrodt

Xiang Xu

Joane Litvak

Sambaiah Thota

Rao Kolluri

Vanessa Taylor

Esteban Masuda

Yan Chen

Todd M Kinsella

Marina Gelman

Dane Goff

Simon Shaw

Jeffrey Clough

Matthew Duncton

Ankush Argade

Catherine Sylvain

Robert Michael Borzilleri

Upender Velaparthi

Jayakumar Sankara Warrier

Anthony P Ford

Peiying Liu

David Scott Carter

Andy Atuegbu

Hasibur Rahaman

Zhushou Luo

Wei P Chen

Rose Yen

Chetan Padmakar Darne

Mark Irving

Gary Park

Pingu Ding

Vadim Markovtosov

Beth Fernandez

Vadim Markovtsov

Sambiah Thota

Wei Chen

Chetan Padmakar Dame

The present disclosure is directed to chemical compounds and to the use of such compounds in the treatment of diseases associated with an adrenergic receptor. In certain embodiments of the methods disclosed herein, the methods include administering to the subject a compound as disclosed herein and a peripherally acting P-blocker (PABRA).

Beta adrenergic agonist and methods of using the same

Disclosed herein are kinase inhibitory compounds, such as a receptor-interacting protein-1 (RIP1) kinase inhibitor compounds, as well as pharmaceutical compositions and combinations comprising such inhibitory compounds. The disclosed compounds, pharmaceutical compositions, and/or combinations may be used to treat or prevent a kinase-associated disease or condition, particularly a RIP1-associated disease or condition.

RIP1K inhibitors

Disclosed are pyrazole compounds, as well as pharmaceutical compositions and methods of use thereof. One embodiment is a compound having the structure and pharmaceutically acceptable salts, prodrugs and N-oxides thereof (and solvates and hydrates thereof), wherein A, X, Z, m, p, and Rare as described herein. In certain embodiments, a compound disclosed herein inhibits the activity of one or more members of the TGF-β superfamily, and can be used to treat disease by blocking such activity.

TGF-β inhibitors

Disclosed herein are kinase inhibitory compounds, such as a receptor-interacting protein-1 (RIP1) kinase inhibitor compounds, as well as pharmaceutical compositions and combinations comprising such inhibitory compounds. The disclosed compounds, pharmaceutical compositions, and/or combinations may be used to inhibit a RIP1 kinase in vivo or ex vivo, and also may treat or prevent a kinase-associated disease or condition, particularly a RIP1-associated disease or condition.

RIP1 inhibitory compounds and methods for making and using the same

Disclosed are imidazole compounds, as well as pharmaceutical compositions and methods of use thereof. One embodiment is a compound having the structure and pharmaceutically acceptable salts, prodrugs and N-oxides thereof (and solvates and hydrates thereof), wherein X, Y and Z are as described herein. In certain embodiments, a compound disclosed herein inhibits a cellular TAM receptor, and can be used to treat disease mediated by or involving the TAM receptor family.

Tyrosine kinase inhibitors

Disclosed herein are kinase inhibitory compounds, such as a receptor-interacting protein-1 (RIP1) kinase inhibitor compounds, as well as pharmaceutical compositions and combinations comprising such inhibitory compounds. The compounds may have a structure according to Formula I  The disclosed compounds, pharmaceutical compositions, and/or combinations may be used to treat or prevent a kinase-associated disease or condition, particularly a RIP1-associated disease or condition.

Heterocyclic RIP1 inhibitory compounds

Compounds within the scope of the present invention have a Formula 1 or a salt or produg thereof, where ring A is selected from cycloaliphatic; ring B is aryl; Ris selected from (C1-C10)alkyl, (C3-C10)cycloalkyl, halo, aryl, and heteroaryl; and Rand Rare independently selected from hydrogen and (C1-C6)alkyl. Disclosed compounds may have an IRAK4 ICof from 0.003 &#x3bc;M to 3.7 &#x3bc;M; a TAK1 ICof from 0.008 &#x3bc;M to 132 &#x3bc;M; and/or an IRAK4/TAK1 selectivity of from 1 to 450. Particular compounds may have an IRAK4/TAK1 selectivity of from 100 to 500. Disclosed compositions may be formulated as pharmaceutical compositions. A method for using the compounds and/or compositions also are disclosed. The method may comprise administering to a subject an effective amount of a compound within the scope of the present invention, particularly to selectively inhibit IRAK 1 and/or IRAK4 over TAK1.

2,4-diamino-pyrimidine compounds and method for making and using the compounds

Disclosed are pyrazole compounds, as well as pharmaceutical compositions and methods of use thereof. One embodiment is a compound having the structure and pharmaceutically acceptable salts, prodrugs and N-oxides thereof (and solvates and hydrates thereof), wherein A, X, Z, m, p, and Rare as described herein. In certain embodiments, a compound disclosed herein inhibits the activity of one or more members of the TGF-&#x3b2; superfamily, and can be used to treat disease by blocking such activity.

TGF-&#x3b2; inhibitors

Disclosed are imidazole and thiazole compounds, as well as pharmaceutical compositions and methods of use thereof. One embodiment is a compound having the structure and pharmaceutically acceptable salts, prodrugs and N-oxides thereof (and solvates and hydrates thereof), wherein X, A, Z, Rand R' are as described herein. In certain embodiments, a compound disclosed herein inhibits TGF-&#x3b2;, and can be used to treat disease by blocking TGF-&#x3b2; signaling.

TGF-beta inhibitors

Aspects of the present disclosure include compounds that find use for the treatment of a variety of autoimmune and inflammatory diseases and disorders. Embodiments of the present disclosure also relate to pharmaceutical compositions that include these compounds, methods of using these compounds in the treatment of various diseases and disorders, processes for preparing these compounds and intermediates useful in these processes.

Fumarate analogs and uses thereof

Disclosed are imidazole compounds, as well as pharmaceutical compositions and methods of use thereof. One embodiment is a compound having the structure  and pharmaceutically acceptable salts, prodrugs and N-oxides thereof (and solvates and hydrates thereof), wherein X, Y and Z are as described herein. In certain embodiments, a compound disclosed herein inhibits a cellular TAM receptor, and can be used to treat disease mediated by or involving the TAM receptor family.

The present disclosure is directed to chemical compounds and to the use of such compounds in the treatment of diseases associated with an adrenergic receptor.

Growing community of inventors

San Carlos, CA, United States of America

Jiaxin Yu