Compounds comprising 4-benzoylpiperidine as a sigma-1-selective ligand
Bipiperidinyl compounds and salts thereof are disclosed. The compounds include high affinity ligands for σ 1 receptors. Some compounds are also highly selective for σ 1 receptor compared to σ 2 receptor. Compounds can comprise radioisotopes, including 18 F or 11 C. Radiolabeled compounds can be used as probes for imaging distribution of σ 1 receptor in a subject such as a human using positron emission tomography (PET) scanning.
1. A compound of structure
or a salt thereof, wherein R 1 is selected from the group consisting of F and OCH 3 , and R 2 is selected from the group consisting of
and wherein the compound exhibits selectivity for σ1 in comparison to vesicular acetylcholine transporter (VAChT), and wherein the compound comprises a positron-emitting nuclide.
2. A compound or salt thereof in accordance with claim 1 , wherein R 1 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 18 F.
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 11 C 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 11 C.
10. A method of imaging distribution of sigma-1 receptors in a subject, comprising:
administering to a subject a radiolabeled compound of structure
or a salt thereof, Wherein R 1 is selected from the group consisting of F and OCH 3 , and R 2 is selected from the group consisting of
and wherein the compound exhibits selectivity for σ1 in comparison to vesicular acetylcholine transporter (VAChT), and wherein the compound comprises a positron-emitting nuclide; and
subjecting the subject to positron emission tomography (PET) scanning.
11. A method in accordance with claim 10 , wherein R 1 is an 18 F.
12. A method in accordance with claim 10 , wherein R 1 is an O 11 CH 3 .
13. A method in accordance with claim 10 , wherein the compound is selected from the group consisting of
wherein an F is an 18 F.
14. A method in accordance with claim 10 , wherein the compound is selected from the group consisting of
wherein an F is an 18 F.
15. A method in accordance with claim 10 , wherein the compound is selected from the group consisting of
wherein an OCH 3 an O 11 CH 3 .
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