IP Library › Granted Patent US 12,226,417
Granted Patent B2
US 12,226,417 · App. 18/101,986 · Granted Feb 18, 2025

Fatty liver disease treatment using glucocorticoid and mineralocorticoid receptor antagonists

Inventors: Joseph K. Belanoff (Menlo Park, CA); Hazel Hunt (Storrington, GB); Onno C. Meijer (Leiden, NL); José van den Heuvel (Leiden, NL)
Assignee: Corcept Therapeutics, Inc.
A61K31/513A61P1/16
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Quick Facts
Patent No.
US 12,226,417
App. No.
18/101,986
Granted
Feb 18, 2025
Kind
B2
Abstract

The present invention provides treatment of fatty liver disease using a class of pyrimidinedione cyclohexyl compounds.

Claims (26)

1. A method of treating fatty liver disease, comprising: administering to a subject in need thereof, a therapeutically effective amount of between 10 milligrams (mg) and 500 mg of a compound of Formula Id,

wherein said administering comprises oral administration of said compound of Formula Id, wherein the compound of Formula Id has the structure:

wherein

each R 1a is independently H, C 1-6 alkyl, halogen, or C 1-6 haloalkyl;

R 2 is H, or C 1-6 alkyl; and

each R 4 is H, C 1-6 alkyl, halogen, or C 1-6 haloalkyl;

or salts or isomers thereof.

2. The method of claim 1 , wherein the fatty liver disease is alcohol-related liver disease (ARLD) or nonalcoholic fatty liver disease (NAFLD).

3. The method of claim 2 , wherein the alcohol-related liver disease is selected from alcohol fatty liver disease (AFL), alcoholic steatohepatitis (ASH) and alcoholic cirrhosis.

4. The method of claim 2 , wherein the nonalcoholic fatty liver disease is selected from nonalcoholic steatohepatitis (NASH) and nonalcoholic cirrhosis.

5. The method of claim 1 , wherein each R 1a is C 1-6 haloalkyl.

6. The method of claim 1 , wherein each R 1a is independently selected from the group consisting of H, Me, Et, F, Cl, or —CF 3 .

7. The method of claim 1 , wherein each R 1a is —CF 3 .

8. The method of claim 1 , wherein R 2 is H.

9. The method of claim 1 , wherein the compound of Formula Id is selected from the group consisting of:

10. The method of claim 1 , the compound of Formula Id having the formula:

11. The method of claim 1 , wherein said compound of Formula Id is an antagonist of the glucocorticoid receptor.

12. The method of claim 1 , wherein said compound of Formula Id is an antagonist of the mineralocorticoid receptor.

13. The method of claim 1 , wherein said compound of Formula Id inhibits glucocorticoid binding to the glucocorticoid receptor and is an antagonist of the mineralocorticoid receptor.

14. The method of claim 1 , wherein said compound of Formula Id inhibits glucocorticoid binding to the glucocorticoid receptor with an inhibition constant (K i ) of between about 0.0001 nanomolar (nM) to 1000 nM and is an antagonist of the mineralocorticoid receptor.

15. The method of claim 13 , wherein said fatty liver disease is an alcohol-related fatty liver disease.

16. The method of claim 14 , wherein said fatty liver disease is an alcohol-related fatty liver disease.

17. The method of claim 13 , wherein said fatty liver disease is a nonalcoholic fatty liver disease.

18. The method of claim 14 , wherein said fatty liver disease is a nonalcoholic fatty liver disease.

19. The method of claim 17 , wherein said nonalcoholic fatty liver disease is selected from nonalcoholic steatohepatitis (NASH) and nonalcoholic cirrhosis.

20. The method of claim 18 , wherein said nonalcoholic fatty liver disease is selected from nonalcoholic steatohepatitis (NASH) and nonalcoholic cirrhosis.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 27, 2023
From: BELANOFF, JOSEPH K.; HUNT, HAZEL; MEIJER, ONNO C.; VAN DEN HEUVEL, JOSE
To: CORCEPT THERAPEUTICS, INC.
Reel/Frame 062508/0323 →
Continuity (6)
Continuation 17111288 · Dec 3, 2020
Continuation 16256295 · Jan 24, 2019
Continuation 14883369 · Oct 14, 2015
Provisional Application 62092041 · Dec 15, 2014
Provisional Application 62064358 · Oct 15, 2014
Related Publication 20230218621A1 · Jul 13, 2023
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