Derivatives of sobetirome

Patent metadata

Field	Value
Publication number	US-10870616-B2
Application number	US-201916707604-A
Country	US
Kind code	B2
Filing date	Dec 9, 2019
Priority date	May 18, 2016
Publication date	Dec 22, 2020
Grant date	Dec 22, 2020

Abstract

Disclosed are halo substituted derivative compounds of sobetirome with improved pharmacological characteristics relative to sobetirome, pharmaceutical compositions that include those compounds and methods of treating diseases such as neurodegenerative disorders using those pharmaceutical compositions.

First claim

What is claimed is:

1. A method of treating a neurodegenerative disorder, the method comprising administering an effective amount of a compound of Formula (I):

or a pharmaceutically acceptable salt thereof, to a subject in need thereof, thereby treating the neurodegenerative disorder, wherein R 1 and R 2 are both chloro, R 3 is —NHR 3b and R 3b is methyl.

2. The method of claim 1 , wherein the neurodegenerative disorder is a demyelinating disease.

3. The method of claim 1 , where the neurodegenerative disorder is X-linked adrenoleukodystrophy.

4. A unit dosage form comprising a compound of Formula (I):

wherein:
R 1 and R 2 are independently fluoro, chloro, bromo, or iodo;
R 3 is —OH or —NR 3a R 3b ;
R 3a is hydrogen or C 1-6 alkyl; and

R 3b is C 1-6 alkyl;
or a pharmaceutically acceptable salt thereof.

5. The unit dosage form of claim 4 , wherein R 1 and R 2 are independently chloro or bromo, or a pharmaceutically acceptable salt thereof.

6. The unit dosage form of claim 4 , wherein R 1 and R 2 are both bromo, or a pharmaceutically acceptable salt thereof.

7. The unit dosage form of claim 6 , wherein R 3 is OH, and the compound has the following structure:

a pharmaceutically acceptable salt thereof.

8. The unit dosage form of claim 7 , wherein the compound is in the form of the free acid.

9. The unit dosage form of claim 8 , wherein the unit dosage form is a tablet or capsule.

10. The unit dosage form of claim 6 , wherein R 3 is —NHR 3b and R 3b is C 1-6 alkyl, or a pharmaceutically acceptable salt thereof.

11. The unit dosage form of claim 10 , wherein R 3b is methyl, and the compound has the following structure:

or a pharmaceutically acceptable salt thereof.

12. The unit dosage form of claim 11 , wherein the compound is in the form of the free base.

13. The unit dosage form of claim 12 , wherein the unit dosage form is a tablet or capsule.

14. The unit dosage form of claim 4 , wherein R 1 and R 2 are both chloro, or a pharmaceutically acceptable salt thereof.

15. The unit dosage form of claim 14 , wherein R 3 is —OH, and the compound has the following structure:

a pharmaceutically acceptable salt thereof.

16. The unit dosage form of claim 15 , wherein the compound is in the form of the free acid.

17. The unit dosage form of claim 16 , wherein the unit dosage form is a tablet or capsule.

18. The unit dosage form of claim 14 , wherein R 3 is —NHR 3b and R 3b is C 1-6 alkyl, or a pharmaceutically acceptable salt thereof.

19. The unit dosage form of claim 18 , wherein R 3b is methyl, and the compound has the following structure:

or a pharmaceutically acceptable salt thereof.

20. The unit dosage form of claim 19 , wherein the compound is in the form of the free base.

21. The unit dosage form of claim 20 , wherein the unit dosage form is a tablet or capsule.

22. A method of treating a neurodegenerative disorder, the method comprising administering to a subject in need thereof an effective amount of a unit dosage form of claim 4 .

23. The method of claim 22 , wherein the neurodegenerative disorder is a demyelinating disease.

24. The method of claim 22 , wherein the neurodegenerative disorder is X-linked adrenoleukodystrophy.

25. The method of claim 22 , wherein the neurodegenerative disorder is multiple sclerosis.

Assignees

• Univ Oregon Health & Science

Inventors

• Scanlan Thomas
• Devereaux Jordan
• Placzek Andrew
• Banerji Tapasree
• Ferrara Skylar
• Meinig James Matthew
• Banerji Tania

Classifications

• C07C235/20 Primary

  having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms · CPC title

• C07C37/62 Primary

  by introduction of halogen; by substitution of halogen atoms by other halogen atoms · CPC title

• C07C67/343

  by increase in the number of carbon atoms · CPC title

• C07C67/31

  by introduction of functional groups containing oxygen only in singly bound form · CPC title

• C07C59/70

  Ethers of hydroxy-acetic acid {, e.g. substitutes on the ring} · CPC title