Metabotrophic glutamate receptor 5 modulators and methods of use thereof

• US 9,260,452 B2
• Filed: 06/08/2012
• Issued: 02/16/2016
• 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., Hardy, Larry Wendell, Wu, Frank Xinhe, Saraswat, Lakshmi D., Spear, Kerry L.
• Primary Examiner(s): Leeser, Erich A
• Application Number:
  US14/124,455
• Publication Number:
  US 20140179682A1
• Time in Patent Office: 1,348 Days
• US Class Current: 1/1
• 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:

8. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1 and a pharmaceutically acceptable carrier.

9. A method for treating a disorder or disease mediated by mGluR5, comprising administering to a subject in need thereof a therapeutically effective amount of a compound of claim 1.

10. The method of claim 9, wherein the disorder or disease mediated by mGluR5 is a neurological disorder.

11. The method of claim 10, wherein the neurological disorder is a neurodegenerative disease, a neuropsychiatric disease, an affective disorder, a loss of cognitive function or a learning and memory disorder.

12. A method for treating psychosis, comprising administering to a subject in need thereof a therapeutically effective amount of a compound of claim 1.

13. A method for treating schizophrenia, comprising administering to a subject in need thereof a therapeutically effective amount of a compound of claim 1.

14. A method for treating cognitive impairment associated with schizophrenia, comprising administering to a subject in need thereof a therapeutically effective amount of a compound of claim 1.

15. A method for treating Alzheimer'"'"'s disease, comprising administering to a subject in need thereof a therapeutically effective amount of a compound of claim 1.

16. A method for treating a cognitive disorder, comprising administering to a subject in need thereof a therapeutically effective amount of a compound of claim 1.

17. A method for modulating mGluR5 in a subject by administering to the subject a therapeutically effective amount of a compound of claim 1.

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

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

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

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

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

6. A compound of formula (VII) or a pharmaceutically acceptable salt thereof:

7. A compound selected from: