# US 10,765,652 B2 · Reversible nitroxide derivatives of nitroalkenes that mediate nitrosating and alkylating reactions

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- Number: US 10,765,652 B2
- Document ID: US10765652B2
- Status: Granted
- Kind: B2
- Application number: 16/339,703
- Filed: 2017-10-04
- Published: 2019-09-19
- Granted: 2020-09-08
- Earliest claimed: 2016-10-05
- Assignees: University of Pittsburgh—Of the Commonwealth System of Higher Education
- Applicants: University of Pittsburgh—Of the Commonwealth System of Higher Education
- Inventors: Marco Fazzari; Bruce A. Freeman; Francisco Jose Schopfer
- Web page: https://patentgrep.com/patent/US10765652B2

## CPC

- A61K 31/201: having one or two double bonds, e.g. oleic, linoleic acids
- A61K 9/08: Solutions {(composition of solutions A61K47/00)}
- A61K 9/4858: {Organic compounds}
- A61P 1/04: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
- A61P 3/00: Drugs for disorders of the metabolism (of the blood or the extracellular fluid A61P7/00)
- A61P 3/04: Anorexiants; Antiobesity agents
- A61P 9/08: Vasodilators for multiple indications
- A61P 13/12: of the kidneys
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- C07C 57/02: with only carbon-to-carbon double bonds as unsaturation
- C07C 205/50: having nitro groups and carboxyl groups bound to acyclic carbon atoms of the carbon skeleton
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07C: ACYCLIC OR CARBOCYCLIC COMPOUNDS

## 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.

## Claims

### Claim 1

A composition comprising an effective amount of a fatty acid having a formula:
wherein X1 is H, n is from 1 to 10 and m is from 1 to 10; and
a pharmaceutically acceptable excipient.

### Claim 2 (depends on 1)

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.

### Claim 3 (depends on 1)

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

### Claim 4 (depends on 1)

The composition of claim 1, wherein the —NO2 group is positioned within 7 carbons of the carboxy terminal carbon.

### Claim 5 (depends on 1)

The composition of claim 1, wherein the —NO2 group is positioned within 9 carbons of the carboxy terminal carbon.

### Claim 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 X1 is H, n is from 1 to 10 and m is from 1 to 10; and
a pharmaceutically acceptable excipient.

### Claim 7 (depends on 6)

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

### Claim 8 (depends on 7)

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

### Claim 9 (depends on 6)

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

### Claim 10 (depends on 9)

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

### Claim 11 (depends on 6)

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

### Claim 12 (depends on 11)

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.

### Claim 13 (depends on 6)

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

### Claim 14 (depends on 6)

The method of claim 6, wherein the —NO2 group is positioned within 7 carbons of the carboxy terminal carbon.

### Claim 15 (depends on 6)

The method of claim 6, wherein the —NO2 group is positioned within 9 carbons of the carboxy terminal carbon.

### Claim 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 X1 is H, n is from 1 to 10 and m is from 1 to 10; and
a pharmaceutically acceptable excipient.

### Claim 17 (depends on 16)

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

### Claim 18 (depends on 17)

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

### Claim 19 (depends on 16)

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

### Claim 20 (depends on 19)

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

### Claim 21 (depends on 16)

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

### Claim 22 (depends on 21)

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.

### Claim 23 (depends on 16)

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

### Claim 24 (depends on 16)

The method of claim 16, wherein the —NO2 group is positioned within 7 carbons of the carboxy terminal carbon.

### Claim 25 (depends on 16)

The method of claim 16, wherein the —NO2 group is positioned within 9 carbons of the carboxy terminal carbon.

### Claim 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 X1 is H, n is from 1 to 10 and m is from 1 to 10; and
a pharmaceutically acceptable excipient.

### Claim 27 (depends on 26)

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

### Claim 28 (depends on 27)

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

### Claim 29 (depends on 26)

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

### Claim 30 (depends on 29)

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

### Claim 31 (depends on 26)

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

### Claim 32 (depends on 31)

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.

### Claim 33 (depends on 26)

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

### Claim 34 (depends on 26)

The method of claim 26, wherein the —NO2 group is positioned within 7 carbons of the carboxy terminal carbon.

### Claim 35 (depends on 26)

The method of claim 26, wherein the —NO2 group is positioned within 9 carbons of the carboxy terminal carbon.

### Claim 36

A compound of structure:
wherein X1 is H, n is from 1 to 10 and m is from 1 to 10; and
a pharmaceutically acceptable excipient.

### Claim 37 (depends on 36)

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

### Claim 38 (depends on 36)

The compound of claim 36, wherein the —NO2 group is positioned within 7 carbons of the carboxy terminal carbon.

### Claim 39 (depends on 36)

The compound of claim 36, wherein the —NO2 group is positioned within 9 carbons of the carboxy terminal carbon.