1H-[1, 2, 3] TRIAZOLE SUBSTITUTED AMINO ACIDS AND USES THEREOF

• US 20100278732A1
• Filed: 05/03/2010
• Published: 11/04/2010
• Est. Priority Date: 05/01/2009
• Status: Active Grant

• Current Assignee: Washington University In St Louis
• Original Assignee: Washington University In St Louis
• Inventors: McConathy, Jonathan, Mach, Robert H.
• Granted Patent: US 8,722,014 B2
• Time in Patent Office: Days
• US Class Current: 424/1.89
• CPC Class Codes: A61K 51/0453 having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
• CPC Class Codes: C07B 59/002 Heterocyclic compounds
• CPC Class Codes: C07D 249/04 1,2,3-Triazoles; Hydrogenated 1,2,3-triazoles

Abstract

Tracers for cationic amino acid transport systems and methods of synthesis are disclosed, including compounds comprising a 1H-[1,2,3]triazole moiety. Further disclosed are uses of the analogues, including in vivo imaging of tumors by Positron emission tomography (PET) or Single Photon Emission Computed Tomography (SPECT).

Claims

1. A radiolabeled 1H-[1,2,3]triazole substituted amino acid or salt thereof of structure

2. A radiolabeled 1H-[1,2,3]triazole substituted amino acid or salt thereof in accordance with claim 1, wherein the F is an ¹⁸F.

3. A radiolabeled 1H-[1,2,3]triazole substituted amino acid or salt thereof in accordance with claim 1, wherein R₁ is CH₂, n is from 1 to 3, m is 0, p is 1, and F is an ¹⁸F

4. A radiolabeled 1H-[1,2,3]triazole substituted amino acid or salt thereof in accordance with claim 1, wherein R₁ is CH₂, n is 1, m is 0, p is 1, and F is an ¹⁸F.

5. A radiolabeled 1H-[1,2,3]triazole substituted amino acid or salt thereof in accordance with claim 1, wherein R₁ is CH₂, n is 2, m is 0, p is 1, and F is an ¹⁸F.

6. A radiolabeled 1H-[1,2,3]triazole substituted amino acid or salt thereof in accordance with claim 1, wherein R₁ is CH₂, n is 3, m is 0, p is 1, and F is an ¹⁸F.

7. A radiolabeled 1H-[1,2,3]triazole substituted amino acid or salt thereof in accordance with claim 1, wherein the acid is selected from the group consisting of

15. A method of imaging a tumor in a mammal, the method comprising:

administering to the mammal a radiolabeled 1H-[1,2,3]triazole substituted amino acid or salt thereof of claim 1; and

subjecting the mammal to PET scanning.

16. A method of imaging a tumor in a mammal in accordance with claim 15, wherein the radiolabeled 1H-[1,2,3]triazole substituted amino acid is selected from the group consisting of

17. A method of imaging a tumor in a mammal in accordance with claim 15, wherein the radiolabeled 1H-[1,2,3]triazole substituted amino acid is selected from the group consisting of

8. A radiolabeled 1H-[1,2,3]triazole substituted amino acid or salt thereof of structure

9. A radiolabeled 1H-[1,2,3]triazole substituted amino acid or salt thereof in accordance with claim 8, wherein the F is an ¹⁸F.

10. A radiolabeled 1H-[1,2,3]triazole substituted amino acid or salt thereof in accordance with claim 8, wherein R₂ is O, z is 1 to 3, y is 1, x is 2, and the F is an ¹⁸F.

11. A radiolabeled 1H-[1,2,3]triazole substituted amino acid or salt thereof in accordance with claim 8, wherein R₂ is O, z is 1, y is 1, x is 2, and the F is an ¹⁸F.

12. A radiolabeled 1H-[1,2,3]triazole substituted amino acid or salt thereof in accordance with claim 8, wherein R₂ is O, z is 2, y is 1, x is 2, and the F is an ¹⁸F.

13. A radiolabeled 1H-[1,2,3]triazole substituted amino acid or salt thereof in accordance with claim 8, wherein R₂ is O, z is 3, y is 1, x is 2, and the F is an ¹⁸F.

14. A radiolabeled 1H-[1,2,3]triazole substituted amino acid or salt thereof in accordance with claim 8, wherein the acid is selected from the group consisting of

18. A method of synthesizing

19. A method of synthesizing