TARGETED NITROXIDE AGENTS

• US 20140018317A1
• Filed: 02/17/2012
• Published: 01/16/2014
• Est. Priority Date: 02/18/2011
• Status: Active Grant

• Current Assignee: University of Pittsburgh of The Commonwealth System of Higher Education
• Original Assignee: University of Pittsburgh of The Commonwealth System of Higher Education
• Inventors: Wipf, Peter, Frantz, Marie-Celine
• Granted Patent: US 9,217,000 B2
• Time in Patent Office: Days
• US Class Current: 514/64
• CPC Class Codes: C07D 209/46 with an oxygen atom in position 1
• CPC Class Codes: C07D 211/94 Oxygen atom, e.g. piperidine N-oxide
• CPC Class Codes: C07D 295/24 Oxygen atoms
• CPC Class Codes: C07D 451/14 containing 9-azabicyclo [3.3.1] nonane ring systems, e.g. granatane, 2-aza-adamantane; Cyclic acetals thereof
• CPC Class Codes: C07D 453/02 containing not further condensed quinuclidine ring systems
• CPC Class Codes: C07D 471/08 Bridged systems
• CPC Class Codes: C07F 5/022 without C-boron linkages
• CPC Class Codes: C07F 9/59 Hydrogenated pyridine rings

Abstract

A compound having a structure of:

Claims

1. A compound having a structure of:

2. The compound of claim 1, wherein R₁ is a C₁-C₆ straight or branched-chain alkyl;

R_1a is H;

R₇ is H or a C₁-C₆ straight or branched-chain alkyl;

R₄ is H;

R₅ is an —

N—

O.—

containing group; and

R is —

C(O)O—

R₆ wherein R₆ is C₁-C₆ straight or branched-chain alkyl.

3. The compound of claim 1, wherein the compound has a structure of:

4. The compound of claim 1, wherein the compound has a structure of:

13. The compound of claim 1, further comprising a detector label moiety coupled to the compound.

14. The compound of claim 13, wherein the detector label moiety comprises a fluorophore covalently bonded to the compound.

15. The compound of claim 1, wherein the compound is in the form of a nitroxide, a hydroxylamine, or a nitroxonium ion.

16. The compound of claim 1, wherein the compound is in the form of a pharmaceutically acceptable salt or ester thereof.

17. A pharmaceutical composition comprising a compound of claim 1, and at least one pharmaceutically acceptable additive.

18. A method of preventing or treating radiation damage in a subject, comprising administering to a subject in need thereof, a therapeutically effective amount of a compound of claim 1.

19. The method of claim 18, wherein the compound is administered after the subject has been exposed to radiation.

20. The method of claim 18, wherein the compound is administered to the subject prior to the subject'"'"'s exposure to radiation.

21. The method of claim 18, wherein the radiation is ionizing radiation.

22. A method of scavenging free radicals in a subject, comprising administering to a subject in need thereof, a therapeutically effective amount of a compound of claim 1.

23. The method of claim 1, wherein the compound is preferentially delivered to the mitochondria.

5. A compound having a structure of:

6. The compound of claim 5, wherein R₂ and R_2a are each a C₁-C₆ straight or branched-chain alkyl.

7. The compound of claim 6, wherein the compound has a structure of:

24. A pharmaceutical composition comprising a compound of claim 5, and at least one pharmaceutically acceptable additive.

26. A method of preventing or treating radiation damage in a subject, comprising administering to a subject in need thereof, a therapeutically effective amount of a compound of claim 5.

8. A compound having a structure of:

25. A pharmaceutical composition comprising a compound of claim 8, and at least one pharmaceutically acceptable additive.

27. A method of preventing or treating radiation damage in a subject, comprising administering to a subject in need thereof, a therapeutically effective amount of a compound of claim 8.

9. A compound having a structure of:

10. The compound of claim 9, wherein R₃ is

11. The compound of claim 10 having a structure of:

12. The compound of claim 9, wherein X is