Ironwood Pharmaceuticals, Inc.

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

The University of North Carolina at Chapel Hill

Dana-Farber-Cancer Institute Inc.

Whitehead Institute for Biomedical Research

Jason Matthew Rohde

Joel D Moore

Takashi Nakai

Charles Kim

Li Liu

Ara Mermerian

Thomas Wai-Ho Lee

Nicholas Robert Perl

Min Shen

Matthew Brian Boxer

Kyle Ryan Brimacombe

Xiaodong Wang

Rajesh R Iyengar

Anton Simeonov

Angelika Fretzen

Ajit Jadhav

Andrew Louis McIver

Rajan Pragani

Mindy Irene Emily Davis

Surendra Karavadhi

David Sabatini

Kevin Sprott

Matthew E Hall

Daniel Jason Urban

Colleen Hudson

James Jia

Ganesha Rai Bantukallu

Natalia Martinez

Michael Pacold

Bo Peng

Wilmin Bartolini

Yuhong Fang

Wei Zhao

Regina Graul

Andrew Louis Mciver

Mindy Irene Davis

Matthew Hall

The present invention provides compounds of Formula (II), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, pro-drugs, and compositions thereof. Also provided are methods and kits involving the compounds of Formula (I), (II) or (III) for treating diseases associated with the over-expression of phosphoglycerate dehydrogenase (PHGDH) in a subject, such as proliferative diseases (e.g., cancers (e.g., breast cancer, ER negative breast cancer, melanoma, cervical cancer), benign neoplasms, diseases associated with angiogenesis, inflammatory diseases, autoinflammatory diseases, and autoimmune diseases). Treatment of a subject with a proliferative disease using a compound or composition of the invention may inhibit the activity of PHGDH or inhibit the serine biosynthetic pathway, or both.

Inhibitors of phosphoglycerate dehydrogenase (PHGDH) and uses thereof

A compound of Formula II or a pharmaceutically acceptable salt thereof, wherein CyN is a cyclic amine group bound via a nitrogen atom; X is C or N; Rand Rare each independently a halogen, CN, CF, CHF, CHF, a C-C10alkyl group, a C1-Calkoxy group, a di(C-Calkyl)amino; m and n are each independently 1, 2, or 3, and represents either a single bond or a double bond, wherein the racemic mixture of 3-(4-(4-chlorophenyl)thiazol-2-yl)-1-(2-ethyl-5-methoxyphenyl)-6-(2-methylprop-1-en-1-yl)-5-(piperazine-1-carbonyl)pyridin-2(1H)-one atropisomers is excluded.

Thiazole derivatives useful as mutant IDH1 inhibitors for treating cancer

Compounds of Formula I and Formula II and the pharmaceutically acceptable salts thereof are disclosed The variables A, B, Y, Z, X, X, Rand Rare disclosed herein. The compounds are useful for treating cancer disorders, especially those involving mutant IDH1 enzymes. Pharmaceutical compositions containing compounds of Formula I or Formula II and methods of treatment comprising administering compounds of Formula I and Formula II are also disclosed. 

Mutant IDH1 inhibitors useful for treating cancer

Compounds of Formula I are described. They are useful as stimulators of sGC, particularly NO-independent, heme-dependent stimulators. These compounds may be useful for treating, preventing or managing various disorders that are herein disclosed. 

SGC stimulators

Compounds of Formula IA and Formula IB are described. They are useful as stimulators of sGC, particularly NO-independent, heme-dependent stimulators. These compounds may be useful for treating, preventing or managing various disorders that are herein disclosed. 

sGC stimulators

Modulators of CRTH2, particularly antagonists of CRTH2, that are useful for treating various disorders, including asthma and respiratory disorders are disclosed. The compounds fall within a genus described by formula I: 

CRTH2 modulators

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Poolesville, MD, United States of America

Jason Matthew Rohde