US 12,291,522 B2
Galectin-3 inhibitors
Chunjian Liu, Pennington, NJ (US); Wei Wang, Princeton, NJ (US); Bruce A. Ellsworth, Princeton, NJ (US); James Aaron Balog, Lambertville, NJ (US); and Alicia Regueiro-Ren, New Hope, PA (US)
Assigned to Bristol-Myers Squibb Company, Princeton, NJ (US)
Appl. No. 17/927,426
Filed by BRISTOL-MYERS SQUIBB COMPANY, Princeton, NJ (US)
PCT Filed May 27, 2021, PCT No. PCT/US2021/034454
§ 371(c)(1), (2) Date Nov. 23, 2022,
PCT Pub. No. WO2021/242982, PCT Pub. Date Dec. 2, 2021.
Claims priority of provisional application 63/030,968, filed on May 28, 2020.
Prior Publication US 2023/0303538 A1, Sep. 28, 2023
Int. Cl. C07H 19/056 (2006.01); C07D 405/14 (2006.01); C07H 17/02 (2006.01)
CPC C07D 405/14 (2013.01) [C07H 19/056 (2013.01)] 16 Claims
 
1. A compound of Formula (I):

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt thereof, wherein:
Ar1 is independently

OG Complex Work Unit Chemistry
Ar2 is independently phenyl or naphthyl; and wherein each ring moiety is substituted with 1 to 5 substituents selected from cyano, halogen, C1-4 alkyl, C1-4 alkoxy, C1-4 haloalkyl, and C1-4 haloalkoxy;
Ar3 is independently phenyl, pyridinyl, quinolone, isoquinoline, or benzothaizolyl, wherein each ring moiety is substituted with 0 to 3 substituents selected from cyano, halogen, C1-4 alkyl, C1-4 haloalkyl;
R1 and R1a are independently H or C1-4 alkyl;
R2 is independently —C(═O)NR3R4 or —OR4;
R3 is independently H, C1-4 alkyl, or C1-4 haloalkyl;
R4 is independently -(L1)1-4-L2-C(═O)NHR5, -(L1)1-4-L2-NHC(═O)R5,
(L1)1-4-NHC(═O)-L2-OR5,

OG Complex Work Unit Chemistry
althernatively, —NR3R4 is independently

OG Complex Work Unit Chemistry
L1 is independently C1-3 alkylene or —C1-3 alkylene-O—;
L2 is independently a bond or C1-3 alkylene;
L3 is independently —O—, —CH2—, —CH2O—, —OCH2—, or —CH2OCH2—;
Ar4 is independently phenylene or pyridinylene; and wherein each ring moiety is substituted with 0 to 2 substituents selected from cyano, halogen, C1-4 alkyl,
C1-4 haloalkyl, C1-4 alkoxy, and C1-4 haloalkoxy;
R5 is independently

OG Complex Work Unit Chemistry
R6 is independently H or C1-4 alkyl;
R7 is independently indolyl substituted with 0 to 2 substituents selected from cyano, halogen, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy, and C1-4 haloalkoxy; and
Ar5 is independently phenylene or pyridinylene; and wherein each ring moiety is substituted with a thiazolyl substituted with 0 to 2 substituents selected from cyano, halogen, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy, and C1-4 haloalkoxy.