US 12,145,922 B2
Selective D3 dopamine receptor agonists and methods of their use
David R. Sibley, Bethesda, MD (US); Amy Elizabeth Moritz, Bethesda, MD (US); R. Benjamin Free, Bethesda, MD (US); Joseph P. Steiner, Bethesda, MD (US); Noel Terrence Southall, Rockville, MD (US); Marc Ferrer, Rockville, MD (US); Xin Hu, Rockville, MD (US); Warren S. Weiner, Boston, MA (US); Jeffrey Aubé, Chapel Hill, NC (US); and Kevin Frankowski, Chapel Hill, NC (US)
Assigned to The United States of America, as represented by the Secretary, Department of Health and Human Services, Bethesda, MD (US); The University of Kansas, Lawrence, KS (US); and The University of North Carolina at Chapel Hill, Chapel Hill, NC (US)
Filed by The United States of America, as represented by the Secretary, Department of Health and Human Services, Bethesda, MD (US); The University of Kansas, Lawrence, KS (US); and The University of North Carolina at Chapel Hill, Chapel Hill, NC (US)
Filed on Feb. 17, 2023, as Appl. No. 18/111,241.
Application 18/111,241 is a continuation of application No. 16/093,365, granted, now 11,634,404, previously published as PCT/US2017/027618, filed on Apr. 14, 2017.
Claims priority of provisional application 62/322,361, filed on Apr. 14, 2016.
Prior Publication US 2023/0312511 A1, Oct. 5, 2023
Int. Cl. C07D 401/12 (2006.01); A61P 25/28 (2006.01); C07D 209/42 (2006.01); C07D 213/65 (2006.01); C07D 213/81 (2006.01); C07D 235/24 (2006.01); C07D 295/185 (2006.01); C07D 307/85 (2006.01); C07D 317/64 (2006.01); C07D 333/70 (2006.01); C07D 405/12 (2006.01); C07D 409/12 (2006.01); C07D 471/04 (2006.01)
CPC C07D 401/12 (2013.01) [A61P 25/28 (2018.01); C07D 209/42 (2013.01); C07D 213/65 (2013.01); C07D 213/81 (2013.01); C07D 235/24 (2013.01); C07D 295/185 (2013.01); C07D 307/85 (2013.01); C07D 317/64 (2013.01); C07D 333/70 (2013.01); C07D 405/12 (2013.01); C07D 409/12 (2013.01); C07D 471/04 (2013.01)] 21 Claims
 
1. A method of treating a patient suffering from Parkinson's disease, dyskinesia, Alzheimer's disease and dementia, Huntington's disease, restless legs syndrome, bipolar disorder and depression, schizophrenia, cognitive dysfunction, alcohol addiction, nicotine addiction, cocaine addiction, methamphetamine addition, and opioid addition, the method comprising administering a therapeutically effective amount of a compound of Formula I

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt thereof, wherein:
W is O or S;
R1 is a phenyl; and
R2 is 2-pyridyl, 3-pyridyl, 4-pyridyl, or pyrolyl group, or a 6,5-bicyclic heteroaryl group, having 1, 2, 3, 4, 5, or 6 heteroatoms independently chosen from N, O, and S, wherein the point of attachment in Formula I is in the 5-membered ring, and the 5-membered ring contains at least one heteroatom; where
R1 and R2 are each optionally substituted with 1 or more substituents independently chosen from halogen, hydroxyl, cyano, nitro, oxo, —CONH2, amino, mono- and di-C1-C4alkylcarboxamide, (C3-C6cycloalkyl)C0-C2alkyl, and C1-Cohydrocarbyl, which C1-C6hydrocarbyl group is a hydrocarbon chain in which the carbon atoms are joined by single, double or triple bonds, and any one carbon atom can be replaced by O, NH, or N(C1-C4alkyl) and which hydrocarbyl group is optionally substituted with one or more substituents independently chosen from hydroxyl, oxo, halogen, and amino; and
R3 and R4 are independently hydrogen or methyl.