Selective NR2B antagonists

• US 9,221,796 B2
• Filed: 01/05/2015
• Issued: 12/29/2015
• Est. Priority Date: 01/09/2014
• Status: Active Grant

• Current Assignee: Bristol-Myers Squibb Company
• Original Assignee: Bristol-Myers Squibb Company
• Inventors: King, Dalton, Thompson, Lorin A. III, Shi, Jianliang, Thangathirupathy, Srinivasan, Warrier, Jayakumar Sankara, Islam, Imadul, Macor, John E.
• Primary Examiner(s): Rozof, Timothy R
• Application Number:
  US14/589,205
• Publication Number:
  US 20150191452A1
• Time in Patent Office: 358 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61K 31/454 containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/02 for peripheral neuropathies
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• 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 401/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 403/04 directly linked by a ring-member-to-ring-member bond

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 piperidinyl substituted with 0-2 halo 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 p-hydroxyphenyl.

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

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

(R)-3-((3S,4R)-3-fluoro-4-(4-hydroxyphenyl)piperidin-1-yl)-1-(4-methylbenzyl)pyrrolidin-2-one

7. The compound of claim 1:

(R)-3-((3S,4S)-3-fluoro-4-(4-hydroxyphenyl)piperidin-1-yl)-1-(4-methylbenzyl)pyrrolidin-2-one or a pharmaceutically acceptable salt thereof

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

9. 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.

10. The method of claim 9 directed to the treatment of depression.

11. The method of claim 9 directed to the treatment of Alzheimer'"'"'s disease.

12. The method of claim 9 directed to the treatment of neuropathic pain.