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US 11,697,646 B2Granted
Triazole N-linked carbamoyl cyclohexyl acids as LPA antagonists
AssigneeBristol-Myers Squibb Company
InventorsYan Shi, Peter Tai Wah Cheng, Ying Wang, Jun Shi, Shiwei Tao, Jun Li, Lawrence J. Kennedy, Robert F. Kaltenbach, III, Hao Zhang, James R. Corte
Life of this patent
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Abstract
The present invention provides compounds of Formula (I): or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein all the variables are as defined herein. These compounds are selective LPA receptor inhibitors.
Claims20
A compound of Formula (IIb):
- 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,
- 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.
20 more elements
Dependencies are inferred from the claim text.