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

University of Pennsylvania

Vanderbilt University

The Uab Research Foundation (the University of Alabama at Birmingham)

Convergene, LLC

Yale University

Shyh Ming Yang

David Joseph Maloney

Ajit Jadhav

Daniel Jason Urban

Anton Simeonov

Alex Gregory Waterson

William J Moore

Gary Allen Sulikowski

Kwangho Kim

Leonard M Neckers

Xin Hu

Plamen P Christov

Kyle Ryan Brimacombe

Victor M Darley-Usmar

Somnath Jana

Chi V Dang

Bryan T Mott

Jennifer L Kouznetsova

Ganesh Rai Bantukallu

Jeffrey William Strovel

Makoto Yoshioka

David J Maloney

Adam Yasgar

Natalia Martinez

Matthew E Hall

Ganesha Rai Bantukallu

Vasilis Vasiliou

Matthew Hall

Brian T Mott

Plamen Christov

The present invention relates to compounds that bind to and otherwise modulate the activity of bromodomain-containing proteins, including BRD4, to processes for preparing these compounds, to pharmaceutical compositions containing these compounds, and to methods of using these compounds for treating a wide variety of conditions and disorders. In particular, this disclosure provides certain BRD4 inhibitors for the treatment of fibrotic diseases or conditions.

Small molecule bromodomain inhibitors and uses therof

Provided is a compound of formula (I) in which Ar, R, U, V, W, X, and p are as described herein. Also provided are methods of using a compound of formula (I), including a method of treating cancer, a method of treating a patient with cancer cells resistant to an anti-cancer agent, and a method of inhibiting lactate dehydrogenase A (LDHA) and/or lactate dehydrogenase B (LDHB) activity in a cell.

Small molecule inhibitors of lactate dehydrogenase and methods of use thereof

The disclosure provides compounds of Formula I, which may be useful as aldehyde dehydrogenase inhibitors and the pharmaceutically acceptable salts thereof. The variables, J, R, G, Q, and ring A are defined herein. Aldehyde dehydrogenase inhibitors of Formula I are useful for treating a variety of conditions including cancer and inflammation. The disclosure includes methods for using compounds and salts of Formula I to treat colon cancer, pancreatic cancer, nasopharyngeal carcinoma, thyroid cancer, prostate cancer, ovarian cancer, head and neck squamous cell carcinoma, lung cancer, hepatocellular carcinoma, leukemia, brain tumors breast cancer, atherosclerosis, ischaemic heart disease, acne vulgaris, asthma, autoimmune diseases, autoinflammatory diseases, chronic prostatitis, glomerulonephritis, inflammatory bowel disease, pelvic inflammatory disease, reperfusion injury, rheumatoid arthritis, sarcoidosis, transplant rejection, vasculitis, and interstitial cystitis. The disclosure also includes pharmaceutical compositions containing a compound or salt of Formula I.

Substituted quinoline analogs as aldehyde dehydrogenase 1A1 (ALDH1A1) inhibitors

The disclosure provides compounds of Formula I, which may be useful as aldehyde dehydrogenase inhibitors and the pharmaceutically acceptable salts thereof. The variables, J, R, G, Q, and ring A are defined herein. Aldehyde dehydrogenase inhibitors of Formula I are useful for treating a variety of conditions including cancer and inflammation. The disclosure includes methods for using compounds and salts of Formula I to treat colon cancer, pancreatic cancer, nasopharyngeal carcinoma, thyroid cancer, prostate cancer, ovarian cancer, head and neck squamous cell carcinoma, lung cancer, hepatocellular carcinoma, leukemia, brain tumors breast cancer, atherosclerosis, ischaemic heart disease, acne vulgaris, asthma, autoimmune diseases, autoinflammatory diseases, chronic prostatitis, glomerulonephritis, inflammatory bowel disease, pelvic inflammatory disease, reperfusion injury, rheumatoid arthritis, sarcoidosis, transplant rejection, vasculitis, and interstitial cystitis. The disclosure also includes pharmaceutical compositions containing a compound or salt of Formula I. 

Provided is a compound of formula (I), in which Ar, R, U, V, W, X, and p are as described herein. Also provided are methods of using a compound of formula (I), including a method of treating cancer, a method of treating a patient with cancer cells resistant to an anti-cancer agent, and a method of inhibiting lactate dehydrogenase A (LDHA) and/or lactate dehydrogenase B (LDHB) activity in a cell.

The present invention relates to compounds that bind to and otherwise modulate the activity of bromodomain-containing proteins, to processes for preparing these compounds, to pharmaceutical compositions containing these compounds, and to methods of using these compounds for treating a wide variety of conditions and disorders.

Small molecule BET bromodomain inhibitors and uses thereof

The disclosure provides a compound of the formula (II) and pharmaceutically acceptable salts thereof. The variables, e.g. n, R, R, R, X, Y, and Z are defined herein. These compounds act as lactate dehydrogenase inhibitors and are useful for treating cancer and fibrosis. The compounds may be particularly useful for treating forms of cancer in which a metabolic switch from oxidative phosphorylation to glycolysis has occurred. The disclosure also provides pharmaceutical compositions containing a compound of this formula and method for treating patients having cancer, fibrosis, or other conditions in which a metabolic switch from oxidative phosphorylation to glycolysis has occurred. 

1 H-pyrazol-1-yl-thiazoles as inhibitors of lactate dehydrogenase and methods of use thereof

The present invention relates to compounds that bind to and otherwise modulate the activity of bromodomain-containing proteins, to processes for preparing these compounds, to pharmaceutical compositions containing these compounds, and to methods of using these compounds for treating a wide variety of conditions and disorders. 

Bicyclic BET bromodomain inhibitors and uses thereof

Provided is a compound of formula (I), in which Ar, R, U, V, W, X, and p are as described herein. Also provided are methods of using a compound of formula (I), including a method of treating cancer, a method of treating a patient with cancer cells resistant to an anti-cancer agent, and a method of inhibiting lactate dehydrogenase A (LDHA) and/or lactate dehydrogenase B (LDHB) activity in a cell. 

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Doylestown, PA, United States of America

Shyh Ming Yang