US 12,466,804 B2
Cyclobutyl carboxylic acids as LPA antagonists
Yan Shi, Flourtown, PA (US); Ying Wang, Belle Mead, NJ (US); Peter Tai Wah Cheng, Princeton, NJ (US); Robert F. Kaltenbach, III, Holland, PA (US); Jun Shi, Princeton, NJ (US); and Shiwei Tao, Hillsborough, NJ (US)
Assigned to Bristol-Myers Squibb Company, Princeton, NJ (US)
Appl. No. 17/617,611
Filed by BRISTOL-MYERS SQUIBB COMPANY, Princeton, NJ (US)
PCT Filed Jun. 16, 2020, PCT No. PCT/US2020/037841
§ 371(c)(1), (2) Date Dec. 9, 2021,
PCT Pub. No. WO2020/257139, PCT Pub. Date Dec. 24, 2020.
Claims priority of provisional application 62/862,959, filed on Jun. 18, 2019.
Prior Publication US 2022/0235027 A1, Jul. 28, 2022
Int. Cl. C07D 401/04 (2006.01); C07D 401/14 (2006.01); C07D 413/14 (2006.01)
CPC C07D 401/04 (2013.01) [C07D 401/14 (2013.01); C07D 413/14 (2013.01)] 12 Claims
 
1. A compound of Formula (I):

OG Complex Work Unit Chemistry
or a stereoisomer, a tautomer, or a pharmaceutically acceptable salt thereof, wherein:
Q1, Q2, and Q3 are independently N, O, NR2a, or CR2b, and the dashed circle denotes bonds forming an aromatic ring; provided that at least one of Q1, Q2, and Q3 is not CR2b;
X1, X2, X3, and X4 are independently CH or CR5; or one of X1, X2, X3, and X4 is N, and the remaining ones are CH or CR5; or two of X1, X2, X3, and X4 are N, and the remaining ones are CH or CR5;
L is independently C1-4 alkylene;
Y is independently selected from:

OG Complex Work Unit Chemistry
 R6, —NR3R6, and —OR7;
R1 is independently

OG Complex Work Unit Chemistry
R2a and R2b are independently selected from H, C1-4 alkyl, C1-4 alkyl (fully or partially deuterated), and C1-4 haloalkyl;
R3 is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, and C1-6 hydroxyalkyl; and the alkyl, by itself or as part of other moiety, is optionally substituted with deuterium partially or fully;
R4 is independently selected from C1-10 alkyl, C1-10 deuterated alkyl (fully or partially deuterated), C1-10 haloalkyl, C1-10 alkenyl, —(C0-4 alkylene)-(C3-8 cycloalkyl), —(C0-4 alkylene)-phenyl, —(C0-4 alkylene)-(3 to 8-membered heterocyclyl), and —(C0-4 alkylene)-(5 to 6-membered heteroaryl); wherein each of the alkyl, alkenyl, cycloalkyl, phenyl, heterocyclyl and heteroaryl, by itself or as part of other moiety, is independently substituted with 0 to 3 R8;
R5 is independently selected from: H, halo, cyano, hydroxyl, amino, C1-6 alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 aminoalkyl, C1-6 alkoxyalkyl, C1-6 alkoxy, and C1-6 haloalkoxy;
R6 and R7 are independently selected from C1-10 alkyl, C1-10 deuterated alkyl (fully or partially deuterated), C1-10 haloalkyl, C1-10 alkenyl, —(C0-4 alkylene)-(C3-8 cycloalkyl), —(C0-4 alkylene)-phenyl, —(C0-4 alkylene)-(3 to 8-membered heterocyclyl), and —(C0-4 alkylene)-(5 to 6-membered heteroaryl); wherein each of the alkyl, alkenyl, cycloalkyl, phenyl, heterocyclyl, and heteroaryl, by itself or as part of other moiety, is independently substituted with 0 to 3 R8;
R8 is each independently selected from deuterium, halo, hydroxyl, amino, cyano, C1-6 alkyl, C1-6 deuterated alkyl (fully or partially deuterated), C2-6 alkenyl, C2-6 alkynyl, C1-6 alkylamino, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 aminoalkyl, C1-6 alkoxyalkyl, C1-6 haloalkoxyalkyl, C1-6 alkoxy, C1-6 haloalkoxy, phenoxy, —O—(C3-6 cycloalkyl), —(C0-4 alkylene)-(C3-8 cycloalkyl), —(C0-4 alkylene)-phenyl, and —(C0-4 alkylene)-(5 to 6-membered heteroaryl);
R9 is independently selected from C1-6 alkyl, C1-6 haloalkyl, —(C0-4 alkylene)-(C3-8 cycloalkyl), —(C0-4 alkylene)-phenyl, —(C0-4 alkylene)-(3 to 8-membered heterocyclyl), and —(C0-4 alkylene)-(5 to 6-membered heteroaryl); wherein each of the C1-6 alkyl, cycloalkyl, phenyl, heterocyclyl, and heteroaryl, by itself or as part of other moiety, is independently substituted with 0 to 3 R10; and
R10 is each independently selected from deuterium, halo, hydroxyl, amino, cyano, C1-6 alkyl, C1-6 deuterated alkyl (fully or partially deuterated), C2-6 alkenyl, C2-6 alkynyl, C1-6 alkylamino, C1-6 haloalkyl, C1-6 hydroxyalkyl, C1-6 aminoalkyl, C1-6 alkoxyalkyl, C1-6 haloalkoxyalkyl, C1-6 alkoxy, and C1-6 haloalkoxy.