Compositions and methods for regulating glucose homeostatsis and insulin action

Patent metadata

Field	Value
Publication number	US-2022017537-A1
Application number	US-202117365528-A
Country	US
Kind code	A1
Filing date	Jul 1, 2021
Priority date	Jun 20, 2012
Publication date	Jan 20, 2022
Grant date	—

Abstract

The present invention encompasses the use of compounds for a novel approach to treat and prevent diseases, conditions, and disorders such as diabetes and ischemic reperfusion injury. Compounds of the invention, including but not limited to BAM15 ((2-fluorophenyl){6-[(2-fluorophenyl)amino](1,2,5-oxadiazolo[3,4-e]pyrazin-5-yl)}amine), a mitochondrial uncoupler, can improve glucose tolerance, increases cellular oxygen consumption, treat or prevent kidney ischemia reperfusion injury reverse insulin resistance, reverse or treat hyperinsulinemia, and reverse or treat hyperlipidemia. The present invention further provides novel compounds as well as methods for identifying compounds with the same or similar properties as BAM15.

First claim

1 . A method for treating cancer, neurodegeneration, heart disease, renal disease, traumatic brain injury, Parkinson's disease, aging, and disorders standing to benefit from increased energy expenditure, said method comprising administering to a subject in need thereof a pharmaceutical composition comprising a pharmaceutically acceptable carrier, optionally at least one additional therapeutic agent, and an effective amount of at least one compound having a structure of Formula I or Formula II:

or active analogs or derivatives thereof,
wherein R 1 -R 10 are all independently optional, and are each independently selected from the group consisting of H, halogen, hydroxy, acyl, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclo, aryl, heteroaryl, alkoxy, amino, amide, thiol, sulfone, sulfoxide, oxo, oxy, nitro, carbonyl, carboxy, amino acid sidechain, and amino acid, wherein each group can be optionally substituted, or a pharmaceutically acceptable salt or prodrug thereof, or

or active analogs and derivatives thereof,
wherein R 1 -R 2 are independently optional, and are each independently selected from the group consisting of H, halogen, hydroxy, acyl, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclo, aryl, heteroaryl, alkoxy, amino, amide, thiol, sulfone, sulfoxide, oxo, oxy, nitro, carbonyl, carboxy, amino acid sidechain, and amino acid, wherein each group can be optionally substituted, or a pharmaceutically acceptable salt or prodrug thereof,
thereby treating a disease, disorder, or condition.

2 - 6 .

7 . The method of claim 1 , wherein said compound is selected from the group consisting of:

8 . The method of claim 1 , wherein said compound is administered at a dosage ranging from about 0.1 mg/kg to about 50 mg/kg body weight.

9 . The method of claim 8 , wherein said compound is administered at a dosage ranging from about 0.5 mg/kg to about 25 mg/kg body weight.

10 . The method of claim 9 , wherein said compound is administered at a dosage ranging from about 1.0 mg/kg to about 5.0 mg/kg body weight.

11 . The method of claim 8 , wherein said compound is administered as a unit dose ranging from about 10 mg to about 500 mg.

12 . The method of claim 1 , wherein said compound is administered more than once.

13 . (canceled)

14 . The method of claim 1 , wherein said compound is BAM15:

15 . The method of claim 1 , wherein said compound increases oxygen consumption.

16 - 39 . (canceled)

Assignees

• Univ Virginia Patent Foundation

Inventors

• Hoehn Kyle
• Kenwood Brandon

Classifications

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61K9/0053

  Mouth and digestive tract, i.e. intraoral and peroral administration · CPC title

• A61P9/04

  Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure · CPC title

• A61K31/4985

  Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems · CPC title

• A61P3/06

  Antihyperlipidemics · CPC title