Therapeutic DNP derivatives and methods using same

• US 10,457,629 B2
• Filed: 08/28/2014
• Issued: 10/29/2019
• Est. Priority Date: 08/30/2013
• Status: Active Grant

• Current Assignee: Yale University
• Original Assignee: Yale University
• Inventors: Shulman, Gerald I., Spiegel, David A.
• Primary Examiner(s): Badio, Barbara P
• Application Number:
  US14/914,408
• Publication Number:
  US 20160207873A1
• Time in Patent Office: 1,888 Days
• CPC Class Codes: A61K 31/085 having an ether linkage to aromatic ring nuclear carbon
• CPC Class Codes: C07C 205/37 the oxygen atom of at least one of the etherified hydroxy groups being further bound to an acyclic carbon atom
• CPC Class Codes: C07J 41/0055 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

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.

Claims

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 μ

moles/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 μ

moles/kg.

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

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