US 11,697,646 B2
Triazole N-linked carbamoyl cyclohexyl acids as LPA antagonists
Yan Shi, Flourtown, PA (US); Peter Tai Wah Cheng, Princeton, NJ (US); Ying Wang, Belle Mead, NJ (US); Jun Shi, San Diego, CA (US); Shiwei Tao, Hillsborough, NJ (US); Jun Li, Pittsburgh, PA (US); Lawrence J. Kennedy, Titusville, NJ (US); Robert F. Kaltenbach, III, Holland, PA (US); Hao Zhang, Belle Mead, NJ (US); and James R. Corte, Yardley, PA (US)
Assigned to Bristol-Myers Squibb Company, Princeton, NJ (US)
Filed by BRISTOL-MYERS SQUIBB COMPANY, Princeton, NJ (US)
Filed on Apr. 7, 2021, as Appl. No. 17/224,161.
Application 17/224,161 is a continuation of application No. 16/744,303, filed on Jan. 16, 2020, granted, now 11,008,300.
Application 16/744,303 is a continuation of application No. 16/223,169, filed on Dec. 18, 2018, granted, now 10,662,172, issued on May 26, 2020.
Claims priority of provisional application 62/607,399, filed on Dec. 19, 2017.
Prior Publication US 2022/0324829 A1, Oct. 13, 2022
This patent is subject to a terminal disclaimer.
Int. Cl. C07D 401/04 (2006.01); C07D 403/04 (2006.01); C07D 249/06 (2006.01); A61P 35/00 (2006.01); A61P 1/16 (2006.01); A61P 19/10 (2006.01); A61P 13/12 (2006.01); A61P 11/00 (2006.01); C07C 249/06 (2006.01); C07C 403/04 (2006.01)
CPC C07D 401/04 (2013.01) [A61P 35/00 (2018.01); C07C 249/06 (2013.01); C07C 403/04 (2013.01); C07D 249/06 (2013.01); C07D 403/04 (2013.01); A61P 1/16 (2018.01); A61P 11/00 (2018.01); A61P 13/12 (2018.01); A61P 19/10 (2018.01)] 20 Claims
 
1. A compound of Formula (IIb):

OG Complex Work Unit Chemistry
or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein:
X1, X2, X3, and X4 are each independently CR6 or N; provided that no more than two of X1, X2, X3, or X4 are N;
R1 is (—CH2)aR9;
a is an integer of 0 or 1;
R2 is each independently halo, cyano, hydroxyl, amino, C1-6 alkyl, C3-6 cycloalkyl, C4-6 heterocyclyl, alkylamino, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxy, alkoxyalkyl, haloalkoxyalkyl, or haloalkoxy;
R3 is independently hydrogen or C1-4 alkyl;
R4 is C1-10 alkyl, C3-8 cycloalkyl, 6 to 10-membered aryl, —(C1-6 alkylene)-(C3-8 cycloalkyl), or —(C1-6 alkylene)-(6 to 10-membered aryl); wherein each of the alkyl, alkenyl, cycloalkyl, aryl, heterocyclyl, and heteroaryl, by itself or as part of other moiety, is independently substituted with 0 to 3 R8; or alternatively, R3 and R4, taken together with the N and O to which they are attached, form a 4- to 6-membered heterocyclic ring moiety which is substituted with 0 to 3 R8;
R5 is hydrogen, C1-6 alkyl, alkylamino, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, haloalkoxyalkyl, alkoxy, or haloalkoxy;
R6 is hydrogen, halo, cyano, hydroxyl, amino, C1-6 alkyl, alkylamino, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, haloalkoxyalkyl, alkoxy, or haloalkoxy;
R7a is independently hydrogen, halo, oxo, cyano, hydroxyl, amino, C1-6 alkyl, C3-6 cycloalkyl, C4-6 heterocyclyl, alkylamino, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, haloalkoxyalkyl, alkoxy, or haloalkoxy;
R8 is each independently deuterium, halo, hydroxyl, amino, cyano, C1-6 alkyl, C1-6 deuterated alkyl, C2-6 alkenyl, C2-6 alkynyl, alkylamino, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, haloalkoxyalkyl, alkoxy, haloalkoxy, —CHO, phenyl, or 5 to 6 membered heteroaryl; or alternatively, two R8, taken together with the atoms to which they are attached, form a 3 to 6-membered carbocyclic ring or a 3 to 6-membered heterocyclic ring each of which is independently substituted with 0 to 3 R12;
R9 is selected from —CN, —C(O)OR10, —C(O)NR11aR11b,

OG Complex Work Unit Chemistry
Re is C1-6 alkyl, C3-6 cycloalkyl, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, or haloalkoxyalkyl;
R10 is hydrogen or C1-10 alkyl;
R11a and R11b are each independently hydrogen, C1-6 alkyl, C3-6 cycloalkyl, C4-6 heterocyclyl, alkylamino, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, haloalkoxyalkyl, alkoxy, or haloalkoxy;
R12 is halo, cyano, hydroxyl, amino, C1-6 alkyl, alkylamino, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, haloalkoxyalkyl, alkoxy, haloalkoxy, phenyl, or 5 to 6 membered heteroaryl;
f is an integer of 0, 1, or 2; and
n is 0 or 1.