Compounds that modulate intracellular calcium
View Patent ↗Described herein are compounds and pharmaceutical compositions containing such compounds, which modulate the activity of store-operated calcium (SOC) channels. Also described herein are methods of using such SOC channel modulators, alone and in combination with other compounds, for treating diseases or conditions that would benefit from inhibition of SOC channel activity.
1. A compound having the structure of Formula (I):
wherein:
R 1 is
L 1 is —NHC(═O)—, —C(═O)NH—, or —N(R 6 )CH 2 —;
R 2 is aryl or heteroaryl, wherein aryl or heteroaryl is substituted with at least one R 3 ;
R 3 is independently selected from halogen, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, or C 1 -C 6 fluoroalkoxy;
R 4 is halogen;
R 5 is optionally substituted aryl, or optionally substituted heteroaryl;
R 6 is H, or C 1 -C 6 alkyl;
R 9 is —CN, —CF 3 , —CF 2 H, C 1 -C 6 alkyl, or C 3 -C 6 cycloalkyl; and
n is an integer selected from 0-2; or
a pharmaceutically acceptable salt, pharmaceutically acceptable solvate, or pharmaceutically acceptable prodrug thereof.
2. The compound of claim 1 wherein L 1 is —NHC(═O)—.
3. The compound of claim 2 wherein R 2 is phenyl substituted with at least one R 3 .
4. The compound of claim 2 wherein R 2 is phenyl substituted with at least two R 3 .
5. The compound of claim 2 wherein R 2 is phenyl substituted with at least three R 3 .
6. The compound of claim 2 wherein R 2 is heteroaryl substituted with at least one R 3 .
7. The compound of claim 6 wherein R 2 is pyridyl substituted with at least one R 3 .
8. The compound of claim 3 wherein each R 3 is independently selected from F and CH 3 .
9. The compound of claim 1 wherein R 9 is C 3 -C 6 cycloalkyl.
10. The compound of claim 9 wherein R 9 is cyclopropyl.
11. The compound of claim 1 wherein R 9 is —CF 3 .
12. The compound of claim 1 wherein R 5 is optionally substituted aryl.
13. The compound of claim 12 wherein R 5 is optionally substituted phenyl.
14. The compound of claim 1 wherein R 5 is optionally substituted heteroaryl.
15. The compound of claim 14 wherein R 5 is optionally substituted thiazolyl.
16. The compound of claim 14 wherein R 5 is optionally substituted oxazolyl.
17. The compound of claim 1 wherein n is 0.
18. The compound of claim 1 wherein n is 1.
19. The compound of claim 18 wherein R 4 is F.
20. A compound having the structure of Formula (II):
wherein:
R 1 is
L 1 is —NHC(═O)—, —C(═O)NH—, or —N(R 6 )CH 2 —;
Y is CR 8 , or N;
R 2 is aryl or heteroaryl, wherein aryl or heteroaryl is substituted with at least one R 3 ;
R 3 is independently selected from halogen, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, or C 1 -C 6 fluoroalkoxy;
R 4 is halogen;
R 5 is optionally substituted aryl, or optionally substituted heteroaryl;
R 6 is H, or C 1 -C 6 alkyl;
R 8 is H, or halogen;
R 9 is —CN, —CF 3 , —CF 2 H, C 1 -C 6 alkyl, or C 3 -C 6 cycloalkyl; and
n is an integer selected from 0-2; or
a pharmaceutically acceptable salt, pharmaceutically acceptable solvate, or pharmaceutically acceptable prodrug thereof.
21. A pharmaceutical composition comprising a pharmaceutically acceptable diluent, excipient, carrier or binder, and a compound of claim 1 or a pharmaceutically acceptable salt, pharmaceutically acceptable prodrug, or pharmaceutically acceptable solvate thereof.