Reversible nitroxide derivatives of nitroalkenes that mediate nitrosating and alkylating reactions

Patent metadata

Field	Value
Publication number	US-10765652-B2
Application number	US-201716339703-A
Country	US
Kind code	B2
Filing date	Oct 4, 2017
Priority date	Oct 5, 2016
Publication date	Sep 8, 2020
Grant date	Sep 8, 2020

Abstract

Various embodiments of this invention are directed to pharmaceutical compositions and methods for treating disease. The compositions of such embodiments include reversible nitroxide derivatives of nitroalkenes. The methods of various embodiments include administering an effective amount of any of these pharmaceutical compositions to a patient in need of treatment.

First claim

What is claimed is:

1. A composition comprising an effective amount of a fatty acid having a formula:

wherein X 1 is H, n is from 1 to 10 and m is from 1 to 10; and
a pharmaceutically acceptable excipient.

2. The composition of claim 1 , wherein the fatty acid is esterified into a complex lipid selected from the group consisting of diglycerides, triglycerides, phospholipids, glycolipids, and cholesteryl esters.

3. The composition of claim 1 , wherein the fatty acid is:

4. The composition of claim 1 , wherein the —NO 2 group is positioned within 7 carbons of the carboxy terminal carbon.

5. The composition of claim 1 , wherein the —NO 2 group is positioned within 9 carbons of the carboxy terminal carbon.

6. A method of delivering nitric oxide comprising administering to a subject in need thereof an effective amount of a fatty acid having a formula:

wherein X 1 is H, n is from 1 to 10 and m is from 1 to 10; and
a pharmaceutically acceptable excipient.

7. The method of claim 6 , wherein a nitic oxide molecule is released.

8. The method of claim 7 , wherein the released nitric oxide molecule induces vasodilation.

9. The method of claim 6 , wherein a nitrated linoleic acid molecule is released.

10. The method of claim 9 , wherein the nitrated linoleic acid molecule provides protection from metabolic and inflammatory stress.

11. The method of claim 6 , wherein negative side effects of a subject's gastrointestinal tract are reduced.

12. The method of claim 11 , wherein the side effects of the gastrointestinal tract is selected from the group consisting of diarrhea, cramping irritation, inflammatory bowel disease, colitis, and ulcers.

13. The method of claim 6 , wherein the fatty acid is:

14. The method of claim 6 , wherein the —NO 2 group is positioned within 7 carbons of the carboxy terminal carbon.

15. The method of claim 6 , wherein the —NO 2 group is positioned within 9 carbons of the carboxy terminal carbon.

16. A method of treating inflammation, obesity, metabolic syndrome, acute kidney disease, or chronic kidney disease comprising administering to a subject in need thereof an effective amount of a fatty acid having a formula:

wherein X 1 is H, n is from 1 to 10 and m is from 1 to 10; and
a pharmaceutically acceptable excipient.

17. The method of claim 16 , wherein a nitic oxide molecule is released.

18. The method of claim 17 , wherein the released nitric oxide molecule induces vasodilation.

19. The method of claim 16 , wherein a nitrated linoleic acid molecule is released.

20. The method of claim 19 , wherein the nitrated linoleic acid molecule provides protection from metabolic and inflammatory stress.

21. The method of claim 16 , wherein negative side effects of a subject's gastrointestinal tract are reduced.

22. The method of claim 21 , wherein the side effects of the gastrointestinal tract is selected from the group consisting of diarrhea, cramping irritation, inflammatory bowel disease, colitis, and ulcers.

23. The method of claim 16 , wherein the fatty acid is:

24. The method of claim 16 , wherein the —NO 2 group is positioned within 7 carbons of the carboxy terminal carbon.

25. The method of claim 16 , wherein the —NO 2 group is positioned within 9 carbons of the carboxy terminal carbon.

26. A method of inducing vasodilation comprising administering to a subject in need thereof an effective amount of a fatty acid having a formula:

wherein X 1 is H, n is from 1 to 10 and m is from 1 to 10; and
a pharmaceutically acceptable excipient.

27. The method of claim 26 , wherein a nitic oxide molecule is released.

28. The method of claim 27 , wherein the released nitric oxide molecule induces vasodilation.

29. The method of claim 26 , wherein a nitrated linoleic acid molecule is released.

30. The method of claim 29 , wherein the nitrated linoleic acid molecule provides protection from metabolic and inflammatory stress.

31. The method of claim 26 , wherein negative side effects of a subject's gastrointestinal tract are reduced.

32. The method of claim 31 , wherein the side effects of the gastrointestinal tract is selected from the group consisting of diarrhea, cramping irritation, inflammatory bowel disease, colitis, and ulcers.

33. The method of claim 26 , wherein the fatty acid is:

34. The method of claim 26 , wherein the —NO 2 group is positioned within 7 carbons of the carboxy terminal carbon.

35. The method of claim 26 , wherein the —NO 2 group is positioned within 9 carbons of the carboxy terminal carbon.

36. A compound of structure:

wherein X 1 is H, n is from 1 to 10 and m is from 1 to 10; and
a pharmaceutically acceptable excipient.

37. The compound of claim 36 , wherein the fatty acid is:

38. The compound of claim 36 , wherein the —NO 2 group is positioned within 7 carbons of the carboxy terminal carbon.

39. The compound of claim 36 , wherein the —NO 2 group is positioned within 9 carbons of the carboxy terminal carbon.

Assignees

• Univ Of Pittsburgh—Of The Commonwealth System Of Higher Education

Inventors

• Fazzari Marco
• Freeman Bruce A
• Schopfer Francisco Jose

Classifications

• C07C205/50

  having nitro groups and carboxyl groups bound to acyclic carbon atoms of the carbon skeleton · CPC title

• A61P9/08

  Vasodilators for multiple indications · CPC title

• A61K31/201 Primary

  having one or two double bonds, e.g. oleic, linoleic acids · CPC title

• A61K9/4858

  Organic compounds · CPC title

• A61K9/08

  Solutions {(composition of solutions A61K47/00)} · CPC title