Nitrated lipids and methods of making and using thereof

Patent metadata

Field	Value
Publication number	US-9867795-B2
Application number	US-201615357731-A
Country	US
Kind code	B2
Filing date	Nov 21, 2016
Priority date	Apr 28, 2004
Publication date	Jan 16, 2018
Grant date	Jan 16, 2018

Abstract

Described herein are nitrated lipids and methods of making and using the nitrated lipids.

First claim

What is claimed:

1. A method for treating vascular disease in a subject in need thereof, comprising administering an effective amount of a lipid having the structure:

wherein:
R 1 is selected from the group consisting of C 1 -C 24 alkyl, C 1 -C 24 alkenyl, and C 1 -C 24 alkynyl;
R 2 , R 3 , R 7 , and R 8 are each independently selected from the group consisting of hydrogen, NO 2 , OH, and OOH, wherein at least one of R 2 , R 3 , R 7 , and R 8 is NO 2 ;
R 4 is C 1 -C 24 alkyl, C 1 -C 24 alkenyl, or C 1 -C 24 alkynyl, wherein R 4 comprises a terminal COOR 6 and R 6 is hydrogen, C 1 -C 24 alkyl, or a pharmaceutically acceptable counterion;
R 5 is hydrogen or R 4 and R 5 collectively form ═C(R 9 )(R 10 ), wherein R 9 is C 1 -C 24 alkyl, C 1 -C 24 alkenyl, or C 1 -C 24 alkynyl and R 10 is hydrogen, NO 2 , OH, or OOH; and
n is from 1 to 24, and a therapeutic agent.

2. The method of claim 1 , wherein the therapeutic agent is selected from a group consisting of antibodies, antivirals, steroidal and non-steroidal anti-inflammatories, conventional immunotherapeutic agents, cytokines, chemokines, and growth factors.

3. The method of claim 1 , wherein the lipid comprises a fatty acid.

4. The method of claim 1 , wherein the lipid is selected from the group consisting of glycolipids, glycerolipids, phospholipids, and cholesterol.

5. The method of claim 1 , wherein the lipid is selected from the group consisting of oleic acid (18:1), 22:6, and docosahexanoic acid.

6. The method of claim 1 , wherein the lipid comprises 10-nitro-9-cis,12-cis-octadecadienoic acid.

7. The method of claim 1 , wherein the lipid is selected from the group consisting of linoleic acid (18:2), linolenic acid (18:3), and cholesterol linoleate.

8. The method of claim 1 , wherein the lipid comprises arachidonic acid (20:4).

9. The method of claim 1 , the lipid having the formula:

wherein:
R 9 is C 1 -C 24 alkyl, C 1 -C 24 alkenyl, or C 1 -C 24 alkynyl and includes a terminal COOR 6 ; and
R 10 is hydrogen, NO 2 , OH, or OOH,
wherein at least one of R 2 , R 3 , R 7 , R 8 , and R 10 is NO 2 .

10. The method of claim 1 , wherein R 1 is C 4 -C 10 alkyl; R 2 , R 8 , and R 10 are hydrogen; R 7 is NO 2 ; and R 9 is C 6 -C 12 alkyl.

11. The method of claim 1 , wherein R 3 and R 8 are cis to one another, and R 7 and R 10 are cis to one another.

12. The method of claim 1 , wherein R 1 is C 4 -C 10 alkyl; R 2 , R 3 , and R 7 are hydrogen; R 8 is NO 2 ; and R 4 is C 6 -C 12 alkyl.

13. The method of claim 1 , wherein the lipid comprises 12-nitro-9-cis,12-cis-octadecadienoic acid.

14. The method of claim 1 , wherein R 9 is C 6 -C 12 alkyl.

15. The method of claim 1 , wherein the lipid is 10-nitro-9-cis-octadecaenoic acid.

16. The method of claim 1 , wherein the lipid and the therapeutic agent are administered from a group consisting of concomitantly, simultaneously, and sequentially.

17. The method of claim 1 , wherein the lipid and the therapeutic agent are administered selected from a group consisting of topically, orally, by inhalation, parenterally, intravenously, intraperitoneally, intramuscularly, subcutaneously, intracavity, transdermally, intratracheally, and extracorporeally.

18. The method of claim 1 , wherein the vascular disease is selected from a group consisting of cardiomyopathy, hypertension, atherosclerosis, myocardial infarction, peripheral vascular disease, coronary artery disease, heart failure and stroke.

Assignees

• Uab Res Found
• State Of Oregon Acting By And Through The Board Of Education On Behalf Of The Univ Of Oregon
• Univ College Cardiff Consultants Ltd
• Morehouse School Of Medicine Inc
• The State Of Oregon Acting By And Through The State Board Of Higher Education On Behalf Of The Univ

Inventors

• Freeman Bruce A
• Schopfer Francisco
• O'Donnell Valerie
• Baker Paul
• Chen Yuqing E
• Branchaud Bruce

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title

• A61P25/00

  Drugs for disorders of the nervous system · CPC title