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
X is S, O, or NR S ;
Y is independently selected from CR 10 or N;
R 2 is aryl, heteroaryl, fused aryl or fused heteroaryl; wherein aryl, heteroaryl, fused aryl or fused heteroaryl is optionally substituted with at least one R 3 ;
R 3 is independently selected from the group consisting of H, F, D, Cl, Br, I, —CN, —NO 2 , —OH, —CF 3 , —OCF 3 , —OR 5 , optionally substituted C 1 -C 6 alkyl, optionally substituted C 3 -C 8 cycloalkyl, optionally substituted C 1 -C 6 heteroalkyl, C 1 -C 6 haloalkyl, optionally substituted C 2 -C 8 heterocycloalkyl, optionally substituted aryl, optionally substituted O-aryl, and optionally substituted heteroaryl;
R 5 is selected from the group consisting of H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 3 -C 8 cycloalkyl, phenyl, and benzyl; and
R 9 and R 10 are each independently selected from H, D, optionally substituted C 1 -C 6 alkyl, halogen, C 1 -C 6 alkylcarbonyl, or CF 3 ;
or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate, or pharmaceutically acceptable prodrug thereof.
2. The compound of claim 1 wherein Y is CH.
3. The compound of claim 2 wherein X is O.
4. The compound of claim 3 wherein R 9 is optionally substituted C 1 -C 6 alkyl.
5. The compound of claim 4 wherein R 10 is halogen or optionally substituted C 1 -C 6 alkyl.
6. The compound of claim 5 wherein R 2 is optionally substituted phenyl.
7. The compound of claim 6 wherein R 2 is phenyl substituted with at least one R 3 independently selected from the group consisting of F, Cl, Br, I, and optionally substituted C 1 -C 6 alkyl.
8. The compound of claim 7 wherein R 2 is phenyl substituted with at least one R 3 independently selected from the group consisting F, Cl, and Br.
9. The compound of claim 8 wherein R 10 is optionally substituted C 1 -C 6 alkyl.
10. The compound of claim 9 wherein R 10 is CH 3 .
11. The compound of claim 10 wherein R 9 is CH 3 .
12. The compound of claim 11 wherein R 2 is phenyl substituted with two R 3 and each R 3 is F.
13. The compound of claim 11 wherein R 2 is phenyl substituted with three R 3 and each R 3 is F.
14. The compound of claim 5 wherein R 2 is heteroaryl.
15. The compound of claim 14 wherein R 2 is pyridyl.
16. The compound of claim 15 wherein R 2 is pyridyl substituted with at least one R 3 independently selected from F or Cl.
17. The compound of claim 16 wherein R 2 is pyridyl substituted with two R 3 and each R 3 is F.
18. A pharmaceutical composition comprising a pharmaceutically acceptable diluent, excipient or binder, and a compound of claim 1 or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate, or pharmaceutically acceptable prodrug thereof.