US 11,987,588 B2
Modulators of the beta-3 adrenergic receptor useful for the treatment or prevention of heart failure and disorders related thereto
Thuy-Anh Tran, San Diego, CA (US); Brett Ullman, San Diego, CA (US); Bryan Aubrey Kramer, San Diego, CA (US); Quyen-Quyen Thuy Do, San Diego, CA (US); and Young-Jun Shin, San Diego, CA (US)
Assigned to Arena Pharmaceuticals, Inc., New York, NY (US)
Filed by Arena Pharmaceuticals, Inc., New York, NY (US)
Filed on Apr. 22, 2022, as Appl. No. 17/726,807.
Application 17/726,807 is a continuation of application No. 16/769,507, granted, now 11,339,172, previously published as PCT/US2018/064316, filed on Dec. 6, 2018.
Claims priority of provisional application 62/595,133, filed on Dec. 6, 2017.
Prior Publication US 2022/0396579 A1, Dec. 15, 2022
This patent is subject to a terminal disclaimer.
Int. Cl. C07D 491/048 (2006.01); A61P 9/00 (2006.01); A61P 9/04 (2006.01); C07D 491/10 (2006.01)
CPC C07D 491/048 (2013.01) [A61P 9/00 (2018.01); A61P 9/04 (2018.01); C07D 491/10 (2013.01)] 22 Claims
 
1. A compound selected from compounds of Formula (Ia) and pharmaceutically acceptable salts, solvates, hydrates, and N-oxides thereof:

OG Complex Work Unit Chemistry
wherein:
X is —SO2— or absent;
R1 is selected from: aryl, C1-C6-alkylene-aryl, C1-C6-alkylene-heteroaryl, C3-C7 cycloalkyl, heteroaryl, and heterocyclyl; each optionally substituted with one or more substituents selected from: C1-C6 alkoxy, C1-C6 alkoxycarbonyl, C1-C7 alkyl, C1-C6 alkylamino, C1-C6 alkylcarboxamide, C1-C6 alkylsulfonamido, C1-C6 alkylsulfonyl, amino, aryloxy, arylsulfonyl, carboxamide, carbamimidoyl, carboxy, cyano, C3-C7 cycloalkyl, C2-C8 dialkylamino, C2-C8 dialkylsulfamoyl, C1-C6 haloalkoxy, C1-C6 haloalkyl, halogen, heterocyclyl, hydroxycarbamimidoyl, hydroxyl, oxo, and sulfamoyl; and wherein said C1-C6 alkoxy, C1-C7 alkyl, C1-C6 alkylamino, aryloxy, C3-C7 cycloalkyl, and C2-C8 dialkylamino are each optionally substituted with one or more substituents selected from: amino, C1-C6 alkoxy, C1-C6 alkylamino, C1-C6 alkylcarboxamide, carboxy, —Y—C1-C6-alkylene-Z optionally substituted with oxo, C3-C7 cycloalkyl, cyano, C2-C6 dialkylamino, C1-C6 haloalkyl, C1-C6 haloalkylamino, heterocyclyl, hydroxyl, oxo, and phenyl;
Y is selected from: —O— and —NH—;
Z is selected from: C1-C6 alkoxy, amino, C1-C6 alkylamino, cyano, C2-C6 dialkylamino, hydroxyl, and phenyl;
R2a is H or selected from: C1-C6 alkoxy, C1-C6 alkyl, C3-C7 cycloalkyl, and heterocyclyl; each optionally substituted with one or more substituents selected from: C1-C6 alkoxy, C1-C6 alkylamino, C1-C6 alkyl, C1-C6 alkylenehydroxyl, amino, C3-C7 cycloalkyl, cyano, C2-C8 dialkylamino, heterocyclyl optionally substituted with one oxo group, halogen, hydroxyl, and oxo; and
R2b is H or C1-C6 alkyl.