Selective NR2B antagonists

• US 10,344,020 B2
• Filed: 10/13/2016
• Issued: 07/09/2019
• Est. Priority Date: 10/14/2015
• Status: Active Grant

• Current Assignee: Bristol-Myers Squibb Company
• Original Assignee: Bristol-Myers Squibb Company
• Inventors: Islam, Imadul, Thangathirupathy, Srinivasan, Warrier, Jayakumar Sankara, Cheruku, Srinivas, Shetty, Poornima, Gupta, Grandhi Venkat Ram Krishna Mohan, Macor, John E.
• Primary Examiner(s): Grazier, Nyeemah A
• Application Number:
  US15/767,386
• Publication Number:
  US 20180312491A1
• Time in Patent Office: 999 Days
• Field of Search: 544243, 544295, 544337, 544364, 540542, 540575
• CPC Class Codes: A61P 25/02 for peripheral neuropathies
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 25/24 Antidepressants
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: C07D 401/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 401/14 containing three or more hetero rings
• CPC Class Codes: C07D 403/14 containing three or more hetero rings
• CPC Class Codes: C07D 471/08 Bridged systems
• CPC Class Codes: C07D 487/08 Bridged systems

Abstract

The disclosure generally relates to compounds of formula I, including their salts, as well as compositions and methods of using the compounds. The compounds are ligands of the NR2B receptor and may be useful for the treatment of various disorders of the central nervous system.

Claims

1. A compound of the formula I

2. A compound of claim 1 where n is 1 and ring A is piperazinyl substituted with 0-2 alkyl substituents.

3. A compound of claim 1 where Ar¹ is phenyl substituted with 0-3 substituents selected from cyano, halo, alkyl, haloalkyl, and haloalkoxy.

4. A compound of claim 1 where Ar² is selected from

5. A compound of claim 1 where X is methylene.

6. A compound of claim 1 where R is hydrogen.

7. A compound of claim 1 where R is P(═

O)(OH)₂.

8. A compound of claim 1 selected from the group consisting of

9. A pharmaceutical composition comprising a compound of claim 1 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.

10. A method for the treatment of depression, Alzheimer'"'"'s disease, neuropathic pain, or Parkinson'"'"'s disease, which comprises administering to a patient a therapeutically affective amount of a compound of claim 1.

11. The method of claim 10 directed to the treatment of depression.

12. The method of claim 10 directed to the treatment of Alzheimer'"'"'s disease.

13. The method of claim 10 directed to the treatment of neuropathic pain.