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 5 ;
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 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 H, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 3 -C 8 cycloalkyl, phenyl, and benzyl;
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 ;
R 12 is selected from CN, —OR 5 , optionally substituted C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, and optionally substituted C 3 -C 8 cycloalkyl, optionally substituted aryl, optionally substituted O-aryl, and optionally substituted heteroaryl;
or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate, or pharmaceutically acceptable prodrug thereof.
2. The compound of claim 1 wherein R 2 is phenyl.
3. The compound of claim 2 wherein phenyl is substituted with at least one R 3 independently selected from F, Cl, Br, and I.
4. The compound of claim 1 wherein R 2 is heteroaryl.
5. The compound of claim 4 wherein heteroaryl is pyridyl.
6. The compound of claim 5 wherein pyridyl is substituted with at least one R 3 independently selected from F and Cl.
7. The compound of claim 1 wherein R 1 is
8. The compound of claim 7 wherein R 5 is C 1 -C 6 alkyl; and R 12 is CF 3 .
9. A compound selected from:
or a pharmaceutically acceptable salt, pharmaceutically acceptable solvate, or pharmaceutically acceptable prodrug thereof.
10. A pharmaceutical composition comprising a pharmaceutically acceptable diluent, excipient or binder, and a compound of claim 1 or a pharmaceutically acceptable salt, pharmaceutically acceptable prodrug, or pharmaceutically acceptable solvate thereof.
11. The compound of claim 8 wherein R 2 is phenyl substituted with at least one R 3 independently selected from F, Cl, and Br.
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 is substituted with three R 3 and each R 3 is F.