US 12,275,720 B2
Small molecule inhibitors of galectin-3
Prasada Rao Jalagam, Bangalore (IN); Satheesh Kesavan Nair, Bangalore (IN); Susheel Jethanand Nara, Mumbai (IN); Manoranjan Panda, Yelahanka New Town (IN); Pratik Devasthale, Plainsboro, NJ (US); and Alicia Regueiro-Ren, New Hope, PA (US)
Assigned to Bristol-Myers Squibb Company, Princeton, NJ (US)
Appl. No. 17/921,653
Filed by BRISTOL MYERS SQUIBB, Princeton, NJ (US)
PCT Filed May 4, 2021, PCT No. PCT/US2021/030540
§ 371(c)(1), (2) Date Oct. 27, 2022,
PCT Pub. No. WO2021/226002, PCT Pub. Date Nov. 11, 2021.
Claims priority of provisional application 63/020,041, filed on May 5, 2020.
Prior Publication US 2023/0192672 A1, Jun. 22, 2023
Int. Cl. C07H 19/056 (2006.01); C07D 405/14 (2006.01); C07D 471/04 (2006.01)
CPC C07D 405/14 (2013.01) [C07D 471/04 (2013.01); C07H 19/056 (2013.01); C07B 2200/07 (2013.01)] 13 Claims
 
1. A compound of Formula (I) or Formula (II):

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt thereof, wherein:
X is independently selected from —C(O)—, —CH2—, and —CH2C(O)—;
Ar1 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;
R1 is independently selected from H, C1-4 alkyl, C1-4 haloalkyl, and —CH2C(O)OH;
R2 is independently selected from H, C1-4 alkyl substituted with 0 to 1 OH, C1-4 haloalkyl, —(CH2)0-2—C3-6 cycloalkyl, and —(CH2)0-2-phenyl substituted with 0 to 3 halogen;
R3 is independently C3-6 cycloalkyl or heterocycloalkyl including from 4 to 7 ring atoms, wherein from 1 to 2 ring atoms are each independently selected from N(, N(RB), and O, and S; wherein said ring moiety is substituted with 0 to 1 R5 and 1 R5A;
R5 is independently OH, cyano, halogen, C1-4 haloalkyl, C1-4 alkoxy, C1-4 haloalkoxy, and C1-4 alkyl substituted with 0 to 1 OH;
R5A is independently selected from

OG Complex Work Unit Chemistry
a bicyclic ring selected from

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wherein said bicyclic ring is substituted 0 to 2 R5C;
R5B is independently

OG Complex Work Unit Chemistry
or phenyl substituted with 0 to 2 substituents selected from cyano, halogen, halogen, C1-4 alkyl, C1-4 alkoxy, C1-4 haloalkyl, C1-4 haloalkoxy;
R5C is independently selected from: cyano, halogen, C1-4 alkyl, C1-4 alkoxy, C1-4 haloalkyl, and C1-4 haloalkoxy;
R5D is independently selected from R5C

OG Complex Work Unit Chemistry
phenyl, naphthyl, pyridinyl, and primidinyl, wherein each ring moiety is substituted with 0 to 2 substituents selected from cyano, halogen, C1-4 alkyl, C1-4 alkoxy, C1-4 haloalkyl, C1-4 haloalkoxy;
R5E is independently selected from: H, C1-4 alkyl, Bn, —C(O)(C1-4 alkyl), —C(O)O(C1-4 alkyl), and

OG Complex Work Unit Chemistry
and
R5F is independently —NH-phenyl, wherein said phenyl is substituted with 0 to 2 substituents selected from cyano, halogen, halogen, C1-4 alkyl, C1-4 alkoxy, C1-4 haloalkyl, C1-4 haloalkoxy.