Selective inhibition of gluconeogenic activity

Patent metadata

Field	Value
Publication number	US-11247970-B2
Application number	US-201816496178-A
Country	US
Kind code	B2
Filing date	Mar 21, 2018
Priority date	Mar 22, 2017
Publication date	Feb 15, 2022
Grant date	Feb 15, 2022

Abstract

The present invention provides compounds, pharmaceutical compositions and methods for treating and/or preventing a metabolic condition, such as diabetes.

First claim

The invention claimed is:

1. A compound having a structure of Formula I or a pharmaceutically acceptable salt thereof:

wherein:
each of R 1 , R 2 , R 4 , and R 5 is independently H, halo, optionally substituted alkyl, optionally substituted cycloalkyl or optionally substituted alkoxy;
R 3 is lower alkyl;
R 6 is optionally substituted alkyl or optionally substituted cycloalkyl;
R 7 is H or optionally substituted alkyl; and
R 8 is

2. The compound of claim 1 , wherein R 1 , R 2 , R 4 , and R 5 are independently H, halo, optionally substituted lower alkyl, or optionally substituted lower alkoxy.

3. The compound of claim 1 , wherein R 1 is lower alkyl.

4. The compound of claim 1 , wherein R 2 is lower alkyl.

5. The compound of claim 1 , wherein R 6 is methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, tert-butyl, hexyl, pentyl, cyclopropyl, cyclobutyl cyclopentyl, or cyclohexyl.

6. The compound of claim 1 , wherein R 7 is H.

7. The compound of claim 1 , wherein the compound is selected from

or a pharmaceutically acceptable salt thereof.

8. A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier.

9. A method of treating or preventing a metabolic condition comprising administering to a subject
a compound having a structure of Formula I or a pharmaceutically acceptable salt thereof:

wherein:
each of R 1 , R 2 , R 4 , and R 5 are independently H, halo, optionally substituted alkyl, optionally substituted cycloalkyl or optionally substituted alkoxy;
R 3 is lower alkyl;
R 6 is optionally substituted alkyl or optionally substituted cycloalkyl;
R 7 is H or optionally substituted alkyl; and
R 8 is

or

or a pharmaceutically acceptable salt thereof.

10. The method of claim 9 , further comprising conjointly administering an anti-diabetic drug to the subject.

11. A method of modulating glucose levels in a subject comprising administering to a subject
a compound having a structure of Formula I or a pharmaceutically acceptable salt thereof:

wherein:
each of R 1 , R 2 , R 4 , and R 5 are independently H, halo, optionally substituted alkyl, optionally substituted cycloalkyl or optionally substituted alkoxy;
R 3 is lower alkyl;
R 6 is optionally substituted alkyl or optionally substituted cycloalkyl;
R 7 is H or optionally substituted alkyl; and
R 8 is

or

or a pharmaceutically acceptable salt thereof.

12. The compound of claim 1 , wherein at least one of R 1 , R 2 , R 4 , and R 5 is not H.

13. The method of claim 9 , wherein the method is a method of treating the metabolic condition.

Assignees

• Dana Farber Cancer Inst Inc
• Scripps Research Inst
• Broad Inst Inc

Inventors

• Puigserver Pere
• Sharabi Kfir
• Kamenecka Theodore
• Griffin Patrick
• Schreiber Stuart L
• Schilling Roger
• Nag Partha P
• Bittker Joshua A

Classifications

• A61K45/06 Primary

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• C07D495/04

  Ortho-condensed systems · CPC title

• C07D401/12

  linked by a chain containing hetero atoms as chain links · CPC title

• C07D405/12

  linked by a chain containing hetero atoms as chain links · CPC title

• A61K31/437

  the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline · CPC title