Patent EP-3728216-A1 (EP)
Inventor: SHI YAN
IPC: C07D403/04
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 X 1 , X 2 , X 3 , and X 4  are each independently CR 6  or N; provided that no more than two of X 1 , X 2 , X 3 , or X 4  are N; Q 2  is N or NR 5a ; one of Q 1  and Q 3  is CR 5 , and the other is N or NR 5a ; and the dashed circle denotes optional bonds forming an aromatic ring; Y 1  is O or NR 3 ; Y 2  is -CO-, -SO 2 -, or -S(O(NH)-; Y 3  is O or NR 4a ; provided that (1) Y 1  and Y 3  are not both O, and (2) when Y 2  is C(O), Y 1  is not O; L is a covalent bond or C 1-4  alkylene substituted with 0 to 4 R 7 ; R 1  is (-CH 2 ) a R 9 ; a is an integer of 0 or 1; R 2  is each independently halo, cyano, hydroxyl, amino, C 1-6  alkyl, C 3-6  cycloalkyl, C 4-6  heterocyclyl, alkylamino, haloalkyi, hydroxyalkyi, aminoalkyi, alkoxy, alkoxyalkyl, haloalkoxyalkyl, or haloalkoxy; n is an integer of 0, 1, or 2; R 3  and R 4a  are independently hydrogen, C 1-6  alkyl, haloalkyi, hydroxyalkyi, aminoalkyi, alkoxyalkyl, haloalkoxyalkyl, alkoxy, or haloalkoxy; R 4  is C 1-10  alkyl, C 1-10  haloalkyi, C 1-10  deuterated alkyl, C 1-10  alkenyl, C 3-8  cycloalkyl, 6 to 10-membered aryl, 3 to 8-membered heterocyclyl, -(Ci-6 alkylene)-(C3-8 cycloalkyl), -(C 1-6  alkylene)-(6 to 10-membered aryl), -(C 1-6  alkylene)-(3 to 8-membered heterocyclyl), or -(C 1-6  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, R 3  and R 4 , 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 R 8 ; or alternatively, (R 3  and R 5a ) or (R 3  and R 5 ), 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 R 8 ; R 5a  is hydrogen, C 1-6  alkyl, alkylamino, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, haloalkoxyalkyl, alkoxy, or haloalkoxy; R 5  and R 6  are each independently hydrogen, halo, cyano, hydroxyl, amino, alkyl, alkylamino, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, haloalkoxyalkyl, alkoxy, or haloalkoxy; R 7  is halo, oxo, cyano, hydroxyl, amino, C 1-6  alkyl, C 3-6  cycloalkyl, C 4-6  heterocyclyl, alkylamino, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, haloalkoxyalkyl, alkoxy, or haloalkoxy; R 8  are each independently deuterium, halo, hydroxyl, amino, cyano, C 1-6  alkyl, C 1-6  deuterated alkyl, C 2-6  alkenyl, C 2-6  alkynyl, alkylamino, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, haloalkoxyalkyl, alkoxy, haloalkoxy, phenyl, or 5 to 6-membered heteroaryl; or alternatively, two R 8 , 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 R 12 ; R 9  is selected from -CN, -C(O)OR 10 , -C(O)NR 11a R 11b , -CO-NH-CO-R e , -CO-NH-SO 2 -R e , -CO-NH-SO-R e ,-SO 2 -OH, -SO 2 -NH-CO-R e , -P(O)(OH) 2 , tetrazol-5-yl, -CH 2 -CO-NH-CO-R e , -CH 2 -CO-NH-SO 2 -R e , -CH 2 -CO-NH-SO-R e , -CH 2 -SO 2 -OH, -CH 2 -SO 2 -NH-CO-R e , -CH 2 -P(O)(OH) 2 , tetrazol-5-ylmethylene; R e  is C 1-6  alkyl, C 3-6  cycloalkyl, haloalkyl, hydroxyalkyi, aminoalkyi, alkoxyalkyi, or haloalkoxyalkyi; R 10  is hydrogen or C 1-10  alkyl; and R 11a  and R 11b  are each independently hydrogen, C 1-6  alkyl, C 3-6  cycloalkyl, C 4-6  heterocyclyl, alkylamino, haloalkyi, hydroxyalkyi, aminoalkyi, alkoxyalkyi, haloalkoxyalkyi, alkoxy, or haloalkoxy; and R 12  is halo, cyano, hydroxyl, amino, C 1-6  alkyl, alkylamino, haloalkyi, hydroxyalkyi, aminoalkyi, alkoxyalkyi, haloalkoxyalkyi, alkoxy, haloalkoxy, phenyl, or 5 to 6-membered heteroaryl. These compounds are selective LPA receptor inhibitors.