RADIOLABELED 2-AMINO-4-ALKYL-6-(HALOALKYL)PYRIDINE COMPOUNDS AND THEIR USE IN DIAGNOSTIC IMAGING

• US 20100278751A1
• Filed: 04/30/2010
• Published: 11/04/2010
• Est. Priority Date: 04/30/2009
• Status: Abandoned Application

• Current Assignee: Washington University In St Louis
• Original Assignee: Washington University In St Louis
• Inventors: Welch, Michael, Zhou, Dong, Mach, Robert H.
• Application Number:
  US12/771,040
• Publication Number:
  US 20100278751A1
• Time in Patent Office: Days
• US Class Current: 424/9.44
• CPC Class Codes: A61K 51/0455 having six-membered rings with one nitrogen as the only ring hetero atom
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07D 213/73 Unsubstituted amino or imino radicals

Abstract

Radiolabeled 2-amino-4-alkyl-6-(haloalkyl)pyridine compounds are disclosed. In some aspects, the compounds bind to inducible nitric oxide synthase (iNOS) with high specificity. In some configurations, a compound comprising a radioisotope can be used for diagnostic imaging of iNOS distribution in a mammalian subject such as a human, using a scanning method such as positron emission tomography (PET scanning). Methods of synthesis of the compounds are also disclosed.

Claims

1. A radiolabeled 2-amino-4-alkyl-6-(haloalkyl)pyridine compound or salt thereof of structure

3. A radiolabeled 2-amino-4-alkyl-6-haloalkylpyridine compound or salt thereof in accordance with claim 1, wherein the compound inhibits iNOS with an IC₅₀ of less than or equal to 57.6 nM, or about 57.6 nM, when measured against SEITU, L-NIL and 2-AP as standards.

4. A radiolabeled 2-amino-4-alkyl-6-haloalkylpyridine compound or salt thereof in accordance with claim 1, wherein the compound inhibits iNOS with an IC₅₀ of less than or equal to 54.3 nM, or about 54.3 nM, when measured against SEITU, L-NIL and 2-AP as standards.

5. A radiolabeled 2-amino-4-alkyl-6-haloalkylpyridine compound or salt thereof in accordance with claim 1, wherein R₁ is H or CH₃ and R₂ is CH₃.

6. A radiolabeled 2-amino-4-alkyl-6-haloalkylpyridine compound or salt thereof in accordance with claim 4, wherein R₁ is CH₃ and n=1.

7. A radiolabeled 2-amino-4-alkyl-6-haloalkylpyridine compound or salt thereof in accordance with claim 4, wherein R₁ is H and n=2.

8. A radiolabeled 2-amino-4-alkyl-6-haloalkylpyridine compound or salt thereof in accordance with claim 1, wherein R₁ is ¹¹CH₃.

9. A radiolabeled 2-amino-4-alkyl-6-haloalkylpyridine compound or salt thereof in accordance with claim 1, wherein R₂ is ¹¹CH₃.

10. A radiolabeled 2-amino-4-alkyl-6-haloalkylpyridine compound or salt thereof in accordance with claim 1, wherein the halogen is selected from an F, a Br and an I.

11. A radiolabeled 2-amino-4-alkyl-6-haloalkylpyridine compound or salt thereof in accordance with claim 10, wherein the F is an ¹⁸F.

12. A radiolabeled 2-amino-4-alkyl-6-haloalkylpyridine compound or salt thereof in accordance with claim 10, wherein the Br is a ⁷⁶Br.

13. A radiolabeled 2-amino-4-alkyl-6-haloalkylpyridine compound or salt thereof in accordance with claim 10, wherein the I is a ¹²³I.

14. A radiolabeled 2-amino-4-alkyl-6-haloalkylpyridine compound or salt thereof in accordance with claim 5, wherein n=1, R₁ is a CH₃, X is an ¹⁸F, and R₂ is a CH₃.

15. A radiolabeled 2-amino-4-alkyl-6-haloalkylpyridine compound or salt thereof in accordance with claim 5, wherein n=2, R₁ is an H, X is an ¹⁸F, and R₂ is CH₃.

16. A radiolabeled 2-amino-4-alkyl-6-haloalkylpyridine compound or salt thereof in accordance with claim 1, wherein the compound is selected from the group consisting of

17. A radiolabeled 2-amino-4-alkyl-6-haloalkylpyridine compound or salt thereof in accordance with claim 1, wherein the compound is selected from the group consisting of

18. A salt comprising:

a radiolabeled 2-amino-4-alkyl-6-haloalkylpyridine compound in accordance with claim 1; and

a water soluble anion.

19. A salt in accordance with claim 18, wherein the water soluble anion is an anion of an organic acid.

20. A salt in accordance with claim 18, wherein the anion is an oxalate.

21. A method of imaging iNOS distribution in a mammal, the method comprising:

administering to the mammal a radiolabeled 2-amino-4-alkyl-6-(haloalkyl)pyridine compound or salt thereof, of claim 1; and

subjecting the mammal to PET scanning.

22. A method of imaging iNOS distribution in a mammal in accordance with claim 21, wherein the radiolabeled 2-amino-4-alkyl-6-(haloalkyl)pyridine compound is selected from the group consisting of

23. A method of imaging iNOS distribution in a mammal in accordance with claim 21, wherein the radiolabeled 2-amino-4-alkyl-6-(haloalkyl)pyridine compound is selected from the group consisting of

2. A radiolabeled 2-amino-4-alkyl-6-(haloalkyl)pyridine compound or salt thereof of structure