Compounds comprising 4-benzoylpiperidine as a sigma-1-selective ligand

• US 8,658,131 B2
• Filed: 06/21/2011
• Issued: 02/25/2014
• Est. Priority Date: 06/21/2010
• Status: Active Grant

• Current Assignee: Regents of the University of California (University of California), Washington University In St Louis
• Original Assignee: Washington University In St Louis
• Inventors: Tu, Zhude, Mach, Robert H., Wang, Wei, Parsons, Stanley M.
• Primary Examiner(s): Hartley, Michael G
• Assistant Examiner(s): Donohue, Sean R
• Application Number:
  US13/164,840
• Publication Number:
  US 20110311447A1
• Time in Patent Office: 980 Days
• Field of Search: None
• US Class Current: 424/1.89
• CPC Class Codes: A61K 51/0455 having six-membered rings with one nitrogen as the only ring hetero atom
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/22 Anxiolytics
• 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 401/14 containing three or more hetero rings

Abstract

Bipiperidinyl compounds and salts thereof are disclosed. The compounds include high affinity ligands for σ₁ receptors. Some compounds are also highly selective for σ₁ receptor compared to σ₂ receptor. Compounds can comprise radioisotopes, including ¹⁸F or ¹¹C. Radiolabeled compounds can be used as probes for imaging distribution of σ₁ receptor in a subject such as a human using positron emission tomography (PET) scanning.

Claims

1. A compound of structure

2. A compound or salt thereof in accordance with claim 1, wherein R₁ is F.

3. A compound or salt thereof in accordance with claim 1, wherein the compound is selected from the group consisting of

4. A compound or salt thereof in accordance with claim 3, wherein an F an ¹⁸F.

5. A compound or salt thereof in accordance with claim 1, wherein the compound is selected from the group consisting of

6. A compound or salt thereof in accordance with claim 1, wherein the compound is selected from the group consisting of

7. A compound or salt thereof in accordance with claim 6, wherein a methoxy is an ¹¹C methoxy.

8. A compound or salt thereof in accordance with claim 1, wherein the compound is

9. A compound or salt thereof in accordance with claim 1, wherein at least 1 carbon is a ¹¹C.

10. A method of imaging distribution of sigma-1 receptors in a subject, comprising:

administering to a subject a radiolabeled compound of structure

11. A method in accordance with claim 10, wherein R₁ is an ¹⁸F.

12. A method in accordance with claim 10, wherein R₁ is an O¹¹CH₃.

13. A method in accordance with claim 10, wherein the compound is selected from the group consisting of

14. A method in accordance with claim 10, wherein the compound is selected from the group consisting of

15. A method in accordance with claim 10, wherein the compound is selected from the group consisting of

16. A method in accordance with claim 10, wherein the compound is selected from the group consisting of

17. A method in accordance with claim 10, wherein the compound is