基本信息:
- 专利标题: ISOXAZOLE O-LINKED CARBAMOYL CYCLOHEXYL ACIDS AS LPA ANTAGONISTS
- 申请号:PCT/US2018/066109 申请日:2018-12-18
- 公开(公告)号:WO2019126084A1 公开(公告)日:2019-06-27
- 发明人: CHENG, Peter Tai Wah , KALTENBACH, Robert F., III. , ZHANG, Hao , SHI, Yan , LI, Jun
- 申请人: BRISTOL-MYERS SQUIBB COMPANY
- 申请人地址: Route 206 and Province Line Road Princeton, New Jersey 08543 US
- 专利权人: BRISTOL-MYERS SQUIBB COMPANY
- 当前专利权人: BRISTOL-MYERS SQUIBB COMPANY
- 当前专利权人地址: Route 206 and Province Line Road Princeton, New Jersey 08543 US
- 代理机构: SUN, Jing G. et al.
- 优先权: US62/607,527 20171219
- 主分类号: C07D413/04
- IPC分类号: C07D413/04 ; A61K31/42 ; A61K31/422 ; C07D261/08 ; A61P35/00 ; A61P11/06
摘要:
The present invention provides compounds of Formula (Ia) or (Ib) or a stereoisomer, tautomer, or pharmaceutically acceptable salt or solvate thereof, wherein 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; L is 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, alkoxyalkyi, haloalkoxyallcyl, or haloalkoxy; n is an integer of 0, 1, or 2; R 3 is hydrogen, C 1-6 alkyl, C 1-6 deuterated alkyl, haloalkyi, hydroxyalkyi, aminoalkyi, alkoxyalkyi, haloalkoxyalkyl, alkoxy, or haloalkoxy, and the alkyl, by itself or as part of other moiety, is optionally substituted with deuterium partially or fully; R 4 is C 1-10 alkyl, C 1-10 deuterated alkyl, C 1-10 haloalkyi, C 1-10 alkenyl, C 3-8 cycloalkyl, 6 to 10-membered aryl, 3 to 8-membered heterocyclyl, -(C 1-6 alkylene)-(C 3-8 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 8 ; or alternatively, R 3 and R 4 , taken together with the N atom to which they are attached, form a 4 to 9-membered heterocyclic ring moiety which is substituted with 0 to 3 R; R 5 and R 6 are each independently hydrogen, halo, cyano, hydroxyl, amino, C 1-6 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 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 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, hydroxyalkyl, aminoalkyl, alkoxyalkyl, or haloalkoxyalkyl; 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, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, haloalkoxyalkyl, alkoxy, or haloalkoxy; and R 12 is halo, cyano, hydroxyl, amino, C 1-6 alkyl, alkylamino, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, haloalkoxyalkyl, alkoxy, haloalkoxy, phenyl, or 5 to 6-membered heteroaryl. These compounds are selective LPA receptor inhibitors.
IPC结构图谱:
C | 化学;冶金 |
--C07 | 有机化学 |
----C07D | 杂环化合物 |
------C07D413/00 | 杂环化合物,含两个或更多个杂环,至少有1个环有氮原子和氧原子作为仅有的杂环原子 |
--------C07D413/02 | .含两个杂环 |
----------C07D413/04 | ..被环原子—环原子的键直接连接的 |