Publication number: 20230079399
Abstract: The disclosure provides compounds of Formula I, which may be useful as aldehyde de-hydrogenase inhibitors and the pharmaceutically acceptable salts thereof. The variables, J, R4, 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 tumorsbreast 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.
Type:
Application
Filed:
February 28, 2022
Publication date:
March 16, 2023
Inventors:
Shyh Ming YANG, David J. MALONEY, Natalia MARTINEZ, Adam YASGAR, Anton SIMEONOV
Patent number: 11505559
Abstract: The disclosure provides compounds of Formula I, which may be useful as aldehyde dehydrogenase inhibitors and the pharmaceutically acceptable salts thereof. The variables, J, R4, 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.
Type:
Grant
Filed:
October 30, 2018
Date of Patent:
November 22, 2022
Assignees:
THE UNITED STATES OF AMERICA, AS REPRESENTED BY THE SECRETARY, DEPT. OF HEALTH AND HUMAN SERVICES OFFICE OF TECHNOLOGY TRANSFER, NATIONAL INSTITUTES OF HEALTH, YALE UNIVERSITY
Inventors:
Shyh Ming Yang, David J. Maloney, Natalia Martinez, Adam Yasgar, Anton Simeonov, Vasilis Vasiliou
Patent number: 11247971
Abstract: Provided is a compound of formula (I), in which Ar1, R1, 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.
Type:
Grant
Filed:
January 28, 2021
Date of Patent:
February 15, 2022
Assignees:
THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE UAB RESEARCH FOUNDATION, VANDERBILT UNIVERSITY, THE UNITED STATES OF AMERICA, AS REPRESENTED BY THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES
Inventors:
David J. Maloney, Alex Gregory Waterson, Ganesh Rai Bantukallu, Kyle Ryan Brimacombe, Plamen Christov, Chi V. Dang, Victor Darley-Usmar, Xin Hu, Ajit Jadhav, Somnath Jana, Kwangho Kim, Jennifer L. Kouznetsova, William J. Moore, Bryan T. Mott, Leonard M. Neckers, Anton Simeonov, Gary Allen Sulikowski, Daniel Jason Urban, Shyh Ming Yang
Publication number: 20210179630
Abstract: The disclosure provides compounds of Formula I, which may be useful as aldehyde dehydrogenase inhibitors and the pharmaceutically acceptable salts thereof. The variables, J, R4, 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 tumorsbreast 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.
Type:
Application
Filed:
October 30, 2018
Publication date:
June 17, 2021
Inventors:
Shyh Ming YANG, David J. MALONEY, Natalia MARTINEZ, Adam YASGAR, Anton SIMEONOV, Vasilis VASILIOU
Patent number: 10961200
Abstract: Provided is a compound of formula (I) in which Ar1, R1, 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.
Type:
Grant
Filed:
June 28, 2019
Date of Patent:
March 30, 2021
Assignees:
THE UNITED STATES OF AMERICA, AS REPRESENTED BY THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES, VANDERBILT UNIVERSITY, THE UAB RESEARCH FOUNDATION, THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA
Inventors:
David J. Maloney, Alex Gregory Waterson, Ganesh Rai Bantukallu, Kyle Ryan Brimacombe, Plamen Christov, Chi V. Dang, Victor Darley-Usmar, Xin Hu, Ajit Jadhav, Somnath Jana, Kwangho Kim, Jennifer L. Kouznetsova, William J. Moore, Bryan T. Mott, Leonard M. Neckers, Anton Simeonov, Gary Allen Sulikowski, Daniel Jason Urban, Shyh Ming Yang
Patent number: 10954228
Abstract: The disclosure provides a compound of the formula (II) and pharmaceutically acceptable salts thereof. The variables, e.g. n, R, R3, R10, 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.
Type:
Grant
Filed:
June 29, 2017
Date of Patent:
March 23, 2021
Assignees:
THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, THE UAB RESEARCH FOUNDATION, VANDERBILT UNIVERSITY, NATIONAL INSTITUTES OF HEALTH, UNITED STATES DEPT. OF HEALTH AND HUMAN SERVICES
Inventors:
David J. Maloney, Alex Gregory Waterson, Ganesha Rai Bantukallu, Kyle Ryan Brimacombe, Plamen Christov, Chi V. Dang, Victor M. Darley-Usmar, Matthew Hall, Xin Hu, Ajit Jadhav, Somnath Jana, Kwangho Kim, William J. Moore, Bryan T. Mott, Leonard M. Neckers, Anton Simeonov, Gary Allen Sulikowski, Daniel Jason Urban, Shyh Ming Yang
