Therapeutic DNP derivatives and methods using same

Patent metadata

Field	Value
Publication number	US-10457629-B2
Application number	US-201414914408-A
Country	US
Kind code	B2
Filing date	Aug 28, 2014
Priority date	Aug 30, 2013
Publication date	Oct 29, 2019
Grant date	Oct 29, 2019

Abstract

The present invention includes DNP derivatives of formula (I) that are useful for preventing or treating a metabolic disease or disorder in a subject in need thereof. In certain embodiments, the subject is further administered at least one additional therapeutic agent.

First claim

What is claimed is:

1. A method of ameliorating a disease or disorder in a subject, wherein the disease or disorder is selected from the group consisting of hypertriglyceridemia, fatty liver, and insulin resistance, the method comprising administering to the subject a therapeutically effective amount of 2,4-dinitrophenyl methyl ether or a solvate thereof.

2. The method of claim 1 , wherein the therapeutically effective amount of the 2,4-dinitrophenyl methyl ether or solvate thereof is about 25 μmoles/kg.

3. The method of claim 1 , wherein the method further comprises administering to the subject at least one additional therapeutic agent.

4. The method of claim 3 , wherein the 2,4-dinitrophenyl methyl ether, or solvate thereof, and the at least one additional therapeutic agent are co-administered to the subject.

5. The method of claim 4 , wherein the 2,4-dinitrophenyl methyl ether, or solvate thereof, and the at least one additional therapeutic agent are co-formulated.

6. The method of claim 1 , wherein the subject is a mammal.

7. The method of claim 6 , wherein the mammal is human.

8. A method of increasing energy expenditure in a subject m need thereof, the method comprising administering to the subject a therapeutically effective amount of 2,4-dinitrophenyl methyl ether, or a solvate thereof, whereby energy expenditure in the subject is increased and wherein the subject is afflicted with at least one disease or disorder selected from the group consisting of non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), hepatic steatosis, type 2 diabetes (T2D), acquired lipodystrophy, lipodystrophy (inherited), partial lipodystrophy, hypertriglyceridemia, obesity, metabolic syndrome, Rett's syndrome, Friedreich's ataxia, and insulin resistance.

9. The method of claim 8 , wherein the therapeutically effective amount of the 2,4-dinitrophenyl methyl ether, or solvate thereof, is about 25 μmoles/kg.

10. The method of claim 8 , wherein the subject is a mammal.

11. The method of claim 10 , wherein the mammal is human.

Assignees

• Univ Yale

Inventors

• Shulman Gerald I
• Spiegel David A

Classifications

• C07J41/0055 Primary

  the 17-beta position being substituted by an uninterrupted chain of at least three carbon atoms which may or may not be branched, e.g. cholane or cholestane derivatives, optionally cyclised, e.g. 17-beta-phenyl or 17-beta-furyl derivatives · CPC title

• C07C205/37 Primary

  the oxygen atom of at least one of the etherified hydroxy groups being further bound to an acyclic carbon atom · CPC title

• A61K31/085

  having an ether linkage to aromatic ring nuclear carbon · CPC title