Metabotrophic glutamate receptor 5 modulators and methods of use thereof

• US 9,708,331 B2
• Filed: 02/02/2016
• Issued: 07/18/2017
• Est. Priority Date: 06/08/2011
• Status: Active Grant

• Current Assignee: Sunovion Pharmaceuticals Inc. (Sumitomo Chemical Company Limited)
• Original Assignee: Sunovion Pharmaceuticals Inc. (Sumitomo Chemical Company Limited)
• Inventors: Heffernan, Michele L. R., Wu, Frank Xinhe, Hardy, Larry Wendell, Saraswat, Lakshmi D., Spear, Kerry L.
• Primary Examiner(s): Shameem, Golam M M
• Assistant Examiner(s): DANIEL, LAURA M
• Application Number:
  US15/013,741
• Publication Number:
  US 20160251359A1
• Time in Patent Office: 532 Days
• Field of Search: None
• CPC Class Codes: C07D 471/04 Ortho-condensed systems
• CPC Class Codes: C07D 471/14 Ortho-condensed systems
• CPC Class Codes: C07D 471/20 Spiro-condensed systems
• CPC Class Codes: C07D 487/04 Ortho-condensed systems
• CPC Class Codes: C07D 487/10 Spiro-condensed systems
• CPC Class Codes: C07D 487/14 Ortho-condensed systems
• CPC Class Codes: C07D 487/18 Bridged systems
• CPC Class Codes: C07D 491/147 the condensed system containing one ring with oxygen as ring hetero atom and two rings with nitrogen as ring hetero atom
• CPC Class Codes: C07D 491/20 Spiro-condensed systems
• CPC Class Codes: C07D 491/22 in which the condensed system contains four or more hetero rings
• CPC Class Codes: C07D 498/04 Ortho-condensed systems

Abstract

Compounds that modulate GluR5 activity and methods of using the same are disclosed.

Claims

1. A compound of formula (I) or a pharmaceutically acceptable salt thereof:

6. A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier.

7. A method for modulating mGluR5 in a cell by contacting the cell with an effective amount of a compound of claim 1.

8. The compound of claim 1, wherein R¹, R², R³, R⁴, R⁵, R⁶, R⁷, and R⁸are each independently hydrogen, X, or alkyl.

9. The compound of claim 8, wherein R¹, R², R³, R⁴, R⁵, and R⁶ are each independently hydrogen or alkyl.

10. The compound of claim 8, wherein R⁷ and R⁸ are each independently hydrogen or X.

11. The compound of claim 10, wherein X is F.

2. A compound of formula (IV) or a pharmaceutically acceptable salt thereof:

12. The compound of claim 2, wherein R¹, R², R³, R⁴, R⁵ , and R⁶ are each independently hydrogen or alkyl.

13. The compound of claim 2, wherein R¹ and R², R³ and R⁴, or R⁵ and R⁶ together with the atom to which they are bonded form a heterocycloalkyl ring.

3. A compound of formula (V) or a pharmaceutically acceptable salt thereof:

4. A compound of formula (VI) or a pharmaceutically acceptable salt thereof:

14. The compound of claim 4, wherein R⁷ is cyano.

15. The compound of claim 4, wherein X is F.

5. A compound selected from: