Prodrugs of alpha-ketoglutarate, alpha-ketobutyrate, alpha-ketoisovalerate, and alpha-ketoisohexanoate, and uses thereof

Patent metadata

Field	Value
Publication number	US-11524948-B2
Application number	US-202016916845-A
Country	US
Kind code	B2
Filing date	Jun 30, 2020
Priority date	Oct 17, 2018
Publication date	Dec 13, 2022
Grant date	Dec 13, 2022

Abstract

The present disclosure provides compounds of Formula (VIA), Formula (IIIA), Formula (IVA), and Formula (VA). The compounds are prodrugs of alpha-ketoglutarate, alpha-ketobutryrate, alpha-ketoisovalerate, and alpha-ketoisohexanoate, which are useful in treating or preventing age related diseases, disorders, or conditions.

First claim

We claim:

1. A compound of Formula (VA), or a pharmaceutically acceptable salt thereof:

or
a compound of Formula (IVA), or a pharmaceutically acceptable salt thereof:

wherein
each R 4 is independently selected from unsubstituted and substituted alkyl;
each R 6 is alkyl;
each R 8 is independently selected from H, unsubstituted and substituted alkyl; and
wherein R 4 and R 8 are not substituted with an oxo group.

2. The compound of claim 1 , wherein the compound has the structure of Formula (IVA), or a pharmaceutically acceptable salt thereof:

wherein
each R 6 is alkyl;
R 4 is unsubstituted or substituted alkyl; and
R 8 is H, unsubstituted or substituted alkyl.

3. A compound of the structure of Formula (VA), or a pharmaceutically acceptable salt thereof:

wherein R 4 and R 8 are unsubstituted or substituted alkyl.

4. A compound selected from:

or a pharmaceutically acceptable salt or thereof.

5. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable excipient.

6. The pharmaceutical composition of claim 5 , wherein the pharmaceutical composition is formulated for administration to a mammal by intravenous administration, subcutaneous administration, oral administration, inhalation, nasal administration, dermal administration, or ophthalmic administration.

7. The pharmaceutical composition of claim 5 , wherein the pharmaceutical composition is in the form of a tablet, a pill, a capsule, a liquid, a suspension, a gel, a dispersion, a solution, an emulsion, an ointment, or a lotion.

8. The compound of claim 3 , wherein the compound is

9. A pharmaceutical composition comprising a compound of claim 3 , or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable excipient.

10. The pharmaceutical composition of claim 9 , wherein the pharmaceutical composition is formulated for administration to a mammal by intravenous administration, subcutaneous administration, oral administration, inhalation, nasal administration, dermal administration, or ophthalmic administration.

11. The pharmaceutical composition of claim 9 , wherein the pharmaceutical composition is in the form of a tablet, a pill, a capsule, a liquid, a suspension, a gel, a dispersion, a solution, an emulsion, an ointment, or a lotion.

12. The compound of claim 1 , wherein R 4 and R 8 are optionally substituted with a halogen, a hydroxyl, an alkoxy, a phosphoryl, a phosphate, a phosphonate, a phosphinate, an amino, an amido, an amidine, an imine, a cyano, a nitro, an azido, a sulfhydryl, an alkylthio, a sulfate, a sulfonate, a sulfamoyl, a sulfonamido, a sulfonyl, a heterocyclyl, an aralkyl, or an aromatic or heteroaromatic moiety.

Assignees

• Univ California

Inventors

• Jung Michael E
• Huang Jing
• Xing Yanpeng
• Lomenick Brett E
• Chai Min
• Fu Xudong

Classifications

• C07D265/32

  with oxygen atoms directly attached to ring carbon atoms · CPC title

• C07C69/708

  Ethers · CPC title

• C07D319/12 Primary

  not condensed with other rings · CPC title

• C07C69/007

  Esters of unsaturated alcohols having the esterified hydroxy group bound to an acyclic carbon atom · CPC title

• A61P43/00

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