Derivatives of sobetirome

Patent metadata

Field	Value
Publication number	US-10544075-B2
Application number	US-201716301711-A
Country	US
Kind code	B2
Filing date	May 18, 2017
Priority date	May 18, 2016
Publication date	Jan 28, 2020
Grant date	Jan 28, 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 compound according to Formula I

or any pharmaceutically acceptable salt thereof, wherein:
R 1 and R 2 are independently selected from the group consisting of fluoro, chloro, bromo, and iodo, and
R 3 is independently selected from the group consisting of —OH and —NR 3a R 3b ,
R 3a is independently selected from hydrogen and C 1-6 alkyl, and
R 3b is C 1-6 alkyl.

2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 and R 2 are independently selected from the group consisting of chloro and bromo.

3. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 and R 2 are both bromo.

4. The compound of claim 3 , or a pharmaceutically acceptable salt thereof, wherein R 3 is OH.

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

6. The compound of claim 5 , or a pharmaceutically acceptable salt thereof, wherein R 3b is methyl.

7. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 and R 2 are both chloro.

8. The compound of claim 7 , or a pharmaceutically acceptable salt thereof, wherein R 3 is —OH.

9. The compound of claim 7 , or a pharmaceutically acceptable salt thereof, wherein R 3 is —NHR 3b and R 3b is C 1-6 alkyl.

10. The compound of claim 9 , or a pharmaceutically acceptable salt thereof, wherein R 3b is methyl.

11. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable carriers.

12. A method of treating a neurodegenerative disorder, the method comprising administering an effective amount of a compound according to claim 1 , or a pharmaceutically acceptable salt thereof, to a subject in need thereof, thereby treating the neurodegenerative disorder.

13. The method of claim 12 , wherein the neurodegenerative disorder is a demyelinating disease.

14. The pharmaceutical composition of claim 12 , wherein the neurodegenerative disorder is X-linked adrenoleukodystrophy or multiple sclerosis.

15. The pharmaceutical composition of claim 11 , wherein R 1 and R 2 are both bromo and R 3 is —OH in the compound or the pharmaceutically acceptable salt thereof.

16. The pharmaceutical composition of claim 11 , wherein R 1 and R 2 are both bromo, R 3 is —NHR 3b , and R 3b is methyl in the compound or the pharmaceutically acceptable salt thereof.

17. The pharmaceutical composition of claim 11 , wherein R 1 and R 2 are both chloro and R 3 is —OH in the compound or the pharmaceutically acceptable salt thereof.

18. The pharmaceutical composition of claim 11 , wherein R 1 and R 2 are both chloro, R 3 is —NHR 3b , and R 3b is methyl.

19. The method of claim 12 , wherein R 1 and R 2 are both bromo and R 3 is —OH in the compound or the pharmaceutically acceptable salt thereof, and the neurodegenerative disorder is multiple sclerosis.

20. The method of claim 12 , wherein R 1 and R 2 are both bromo, R 3 is —NHR 3b , and R 3b is methyl in the compound or the pharmaceutically acceptable salt thereof, and the neurodegenerative disorder is multiple sclerosis.

21. The method of claim 12 , wherein R 1 and R 2 are both chloro and R 3 is —OH in the compound or the pharmaceutically acceptable salt thereof, and the neurodegenerative disorder is multiple sclerosis.

22. The method of claim 12 , wherein R 1 and R 2 are both chloro, R 3 is —NHR 3b , and R 3b is methyl, and 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

• C07F7/0803

  Compounds with Si-C or Si-Si linkages · CPC title

• C07C59/68 Primary

  the oxygen atom of the ether group being bound to a non-condensed six-membered aromatic ring · CPC title

• A61P25/00

  Drugs for disorders of the nervous system · CPC title

• C07C65/34

  polycyclic · CPC title

• A61P25/28

  for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia · CPC title