Compounds that modulate intracellular calcium

• US 9,611,263 B2
• Filed: 10/07/2014
• Issued: 04/04/2017
• Est. Priority Date: 10/08/2013
• Status: Active Grant

• Current Assignee: Calcimedica, Inc.
• Original Assignee: Calcimedica, Inc.
• Inventors: Grey, Jonathan, Cao, Jianguo, Wang, Zhijun, Rogers, Evan, Whitten, Jeffrey P.
• Primary Examiner(s): SAEED, KAMAL A
• Application Number:
  US15/028,412
• Publication Number:
  US 20160229845A1
• Time in Patent Office: 910 Days
• Field of Search: None
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: C07D 401/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 417/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 417/14 containing three or more hetero rings

Abstract

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.

Claims

1. A compound having the structure of Formula (I):

2. The compound of claim 1 wherein L₁ is —

NHC(═

O)—

.

3. The compound of claim 2 wherein R₂ is phenyl substituted with at least one R₃.

4. The compound of claim 2 wherein R₂ is phenyl substituted with at least two R₃.

5. The compound of claim 2 wherein R₂ is phenyl substituted with at least three R₃.

6. The compound of claim 2 wherein R₂ is heteroaryl substituted with at least one R₃.

7. The compound of claim 6 wherein R₂ is pyridyl substituted with at least one R₃.

8. The compound of claim 3 wherein each R₃ is independently selected from F and CH₃.

9. The compound of claim 1 wherein R₉ is C₃-C₆cycloalkyl.

10. The compound of claim 9 wherein R₉ is cyclopropyl.

11. The compound of claim 1 wherein R₉ is —

CF₃.

12. The compound of claim 1 wherein R₅ is optionally substituted aryl.

13. The compound of claim 12 wherein R₅ is optionally substituted phenyl.

14. The compound of claim 1 wherein R₅ is optionally substituted heteroaryl.

15. The compound of claim 14 wherein R₅ is optionally substituted thiazolyl.

16. The compound of claim 14 wherein R₅ 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 R₄ is F.

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.

20. A compound having the structure of Formula (II):