US 12,365,653 B2
Small molecule inhibitors of lactate dehydrogenase and methods of use thereof
David J. Maloney, Point of Rocks, MD (US); Alex Gregory Waterson, Nashville, TN (US); Ganesh Rai Bantukallu, Arlington, VA (US); Kyle Ryan Brimacombe, Bethesda, MD (US); Plamen Christov, Nashville, TN (US); Chi V. Dang, Penn Valley, PA (US); Victor Darley-Usmar, Birmingham, AL (US); Xin Hu, Frederick, MD (US); Ajit Jadhav, Chantilly, VA (US); Somnath Jana, Nashville, TN (US); Kwangho Kim, Nashville, TN (US); Jennifer L. Kouznetsova, Silver Spring, MD (US); William J. Moore, Hagerstown, MD (US); Bryan T. Mott, College Park, MD (US); Leonard M. Neckers, Bethesda, MD (US); Anton Simeonov, Bethesda, MD (US); Gary Allen Sulikowski, Nashville, TN (US); Daniel Jason Urban, Rockville, MD (US); and Shyh Ming Yang, Doylestown, PA (US)
Assigned to THE UNITED STATES OF AMERICA, AS REPRESENTED BY THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVIC, Nashville, TN (US); VANDERBILT UNIVERSITY, Nashville, TN (US); The UAB Research Foundation, Birmingham, AL (US); and The Trustees of the University of Pennsylvania, Philadelphia, PA (US)
Filed by THE UNITED STATES OF AMERICA, AS REPRESENTED BY THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES, Bethesda, MD (US); VANDERBILT UNIVERSITY, Nashville, TN (US); The UAB Research Foundation, Birmingham, AL (US); and The Trustees of the University of Pennsylvania, Philadelphia, PA (US)
Filed on Feb. 5, 2024, as Appl. No. 18/433,099.
Application 18/433,099 is a continuation of application No. 17/572,359, filed on Jan. 10, 2022, granted, now 11,897,845.
Application 17/572,359 is a continuation of application No. 17/160,868, filed on Jan. 28, 2021, granted, now 11,247,971.
Application 17/160,868 is a continuation of application No. 16/455,848, filed on Jun. 28, 2019, granted, now 10,961,200.
Application 16/455,848 is a continuation of application No. 15/540,893, granted, now 10,351,532, previously published as PCT/US2015/067895, filed on Dec. 29, 2015.
Claims priority of provisional application 62/097,226, filed on Dec. 29, 2014.
Prior Publication US 2024/0368087 A1, Nov. 7, 2024
This patent is subject to a terminal disclaimer.
Int. Cl. C07D 231/20 (2006.01); A61K 31/415 (2006.01); A61K 31/4155 (2006.01); A61K 31/4178 (2006.01); A61K 31/422 (2006.01); A61K 31/427 (2006.01); A61K 31/437 (2006.01); A61K 31/4439 (2006.01); A61K 31/454 (2006.01); A61K 31/496 (2006.01); A61K 31/501 (2006.01); A61K 31/506 (2006.01); A61K 31/519 (2006.01); A61K 31/5355 (2006.01); A61K 45/06 (2006.01); C07D 231/38 (2006.01); C07D 401/04 (2006.01); C07D 403/04 (2006.01); C07D 403/06 (2006.01); C07D 409/04 (2006.01); C07D 413/04 (2006.01); C07D 417/04 (2006.01); C07D 417/14 (2006.01); C07D 471/04 (2006.01); C07D 495/04 (2006.01); C07D 495/14 (2006.01)
CPC C07D 231/20 (2013.01) [A61K 31/415 (2013.01); A61K 31/4155 (2013.01); A61K 31/4178 (2013.01); A61K 31/422 (2013.01); A61K 31/427 (2013.01); A61K 31/437 (2013.01); A61K 31/4439 (2013.01); A61K 31/454 (2013.01); A61K 31/496 (2013.01); A61K 31/501 (2013.01); A61K 31/506 (2013.01); A61K 31/519 (2013.01); A61K 31/5355 (2013.01); A61K 45/06 (2013.01); C07D 231/38 (2013.01); C07D 401/04 (2013.01); C07D 403/04 (2013.01); C07D 403/06 (2013.01); C07D 409/04 (2013.01); C07D 413/04 (2013.01); C07D 417/04 (2013.01); C07D 417/14 (2013.01); C07D 471/04 (2013.01); C07D 495/04 (2013.01); C07D 495/14 (2013.01)] 12 Claims
 
1. The compound or pharmaceutically acceptable salt thereof, wherein the compound is a compound of formula (Ia-1)

OG Complex Work Unit Chemistry
wherein
R2 is hydrogen, substituted or unsubstituted C1-C8 alkyl, substituted or unsubstituted C1-C8 alkoxy, or halo;
R3 is halo, C1-C8 haloalkyl, C1-C8 haloalkoxy, substituted or unsubstituted C1-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, or substituted or unsubstituted phenyl;
R10 is hydrogen, substituted or unsubstituted C1-C8 alkyl, substituted or unsubstituted cyclopropyl, substituted or unsubstituted —CH2-cyclopropyl, —CH2CH2-cyclopropyl, substituted or unsubstituted —CH═CH2, substituted or unsubstituted —C≡C-cyclopropyl, substituted or unsubstituted phenyl, substituted or unsubstituted benzyl, —I, —CF3, —NH2, or —CN;
n is an integer from 0 to 3; and
m is 0 or an integer from 1-5.