Patent CA-3085347-A1 (CA)
Inventor: SHI YAN
IPC: A61K31/4439
Filed: 2018-12-18
Abstract: The present invention provides compounds of Formula (I) 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; Q2 is N or NR5a; one of Q1 and Q3 is CR5, and the other is N or NR5a; and the dashed circle denotes optional bonds forming an aromatic ring; Y1 is O or NR3; Y2 is -CO-, -SO2-, or -S(O(NH)-; Y3 is O or NR4a; provided that (1) Y1 and Y3 are not both O, and (2) when Y2 is C(O), Y1 is not O; L is a covalent bond or C1-4 alkylene substituted with 0 to 4 R7; 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, haloalkyi, hydroxyalkyi, aminoalkyi, alkoxy, alkoxyalkyl, haloalkoxyalkyl, or haloalkoxy; n is an integer of 0, 1, or 2; R3 and R4a are independently hydrogen, C1-6 alkyl, haloalkyi, hydroxyalkyi, aminoalkyi, alkoxyalkyl, haloalkoxyalkyl, alkoxy, or haloalkoxy; R4 is C1-10 alkyl, C1-10 haloalkyi, C1-10 deuterated alkyl, C1-10 alkenyl, C3-8 cycloalkyl, 6 to 10-membered aryl, 3 to 8-membered heterocyclyl, -(Ci-6 alkylene)-(C3-8 cycloalkyl), -(C1-6 alkylene)-(6 to 10-membered aryl), -(C1-6 alkylene)-(3 to 8-membered heterocyclyl), or -(C1-6 alkylene)-(5 to 6-membered heteroaryl); wherein each of the alkyl, alkylene, alkenyl, cycloalkyl, aryl, heterocyclyl, and heteroaryl, by itself or as part of other moiety, is independently substituted with 0 to 3 R; or alternatively, R3 and R4, taken together with the N and 0 atoms which they are attached, form a 4 to 9-membered heterocyclic ring moiety which is substituted with 0 to 3 R8; or alternatively, (R3 and R5a) or (R3 and R5), taken together with the atoms to which they are attached to, form a 5 to 8-membered heterocyclic ring moiety which is substituted with 0 to 3 R8; R5a is hydrogen, C1-6 alkyl, alkylamino, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, haloalkoxyalkyl, alkoxy, or haloalkoxy; R5 and R6 are each independently hydrogen, halo, cyano, hydroxyl, amino, alkyl, alkylamino, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, haloalkoxyalkyl, alkoxy, or haloalkoxy; R7 is halo, oxo, cyano, hydroxyl, amino, C1-6 alkyl, C3-6 cycloalkyl, C4-6 heterocyclyl, alkylamino, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, haloalkoxyalkyl, alkoxy, or haloalkoxy; R8 are 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, phenyl, or 5 to 6-membered heteroaryl; or alternatively, two R8, taken together with the atom(s) 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, -CO-NH-CO-Re, -CO-NH-SO2-Re, -CO-NH-SO-Re,-SO2-OH, -SO2-NH-CO-Re, -P(O)(OH)2, tetrazol-5-yl, -CH2-CO-NH-CO-Re, -CH2-CO-NH-SO2-Re, -CH2-CO-NH-SO-Re, -CH2-SO2-OH, -CH2-SO2-NH-CO-Re, -CH2-P(O)(OH)2, tetrazol-5-ylmethylene; Re is C1-6 alkyl, C3-6 cycloalkyl, haloalkyl, hydroxyalkyi, aminoalkyi, alkoxyalkyi, or haloalkoxyalkyi; R10 is hydrogen or C1-10 alkyl; and R11a and R11b are each independently hydrogen, C1-6 alkyl, C3-6 cycloalkyl, C4-6 heterocyclyl, alkylamino, haloalkyi, hydroxyalkyi, aminoalkyi, alkoxyalkyi, haloalkoxyalkyi, alkoxy, or haloalkoxy; and R12 is halo, cyano, hydroxyl, amino, C1-6 alkyl, alkylamino, haloalkyi, hydroxyalkyi, aminoalkyi, alkoxyalkyi, haloalkoxyalkyi, alkoxy, haloalkoxy, phenyl, or 5 to 6-membered heteroaryl. These compounds are selective LPA receptor inhibitors.