WITHANOLIDES USEFUL FOR THE TREATMENT OF NEURODEGENERATIVE DISEASES

• US 20190315798A1
• Filed: 06/21/2019
• Published: 10/17/2019
• Est. Priority Date: 11/25/2013
• Status: Active Grant

• Current Assignee: ImStar Therapeutics Inc., Universite Laval
• Original Assignee: ImStar Therapeutics Inc., Universite Laval
• Inventors: Shaw, Anthony A., Julien, Jean-Pierre, Chan, Agnes H.
• Granted Patent: US 11,472,832 B2
• Time in Patent Office: Days
• CPC Class Codes: A61K 31/585 containing lactone rings, e.g. oxandrolone, bufalin
• CPC Class Codes: C07J 71/001 Oxiranes

Abstract

Provided herein are synthetic analogs of withanolide natural products and their pharmaceutical uses in treating neurodegenerative diseases.

Claims

1. A method of treating or preventing a neurodegenerative disease in a patient, the method comprising:

administering to the patient a therapeutically or prophylactically effective amount of a compound Formula (I);

2. The method of claim 1, wherein R¹ and R³ are each independently lower alkyl or alkenyl.

3. The method of claim 2 wherein R¹ and R³ are independently methyl.

4. The method of claim 1, wherein R² and R⁴ are each hydrogens, and the compound has a structure represented by Formula (Ia):

5. The method of claim 4 wherein R¹ is methyl and R³ is hydrogen.

6. The method of claim 4 wherein R¹ is hydrogen and R³ is methyl.

7. The method of claim 4 wherein R¹ is methyl and R³ is methyl.

8. The method of claim 1 wherein the neurodegenerative disease is characterized by TDP-43 proteinopathy.

9. The method of claim 1 wherein the neurodegenerative disease is amyotrophic lateral sclerosis, Alzheimer'"'"'s disease, Parkinson'"'"'s disease, or frontotemporal lobar degeneration.

10. A method of treating or preventing a disease characterized by TDP-43 proteinopathy in a patient comprising administering to the patient a therapeutically or prophylactically effective amount of a compound Formula (I):

11. The method of claim 10, wherein R¹ and R³ are each independently lower alkyl or alkenyl.

12. The method of claim 11 wherein R¹ and R³ are independently methyl.

13. The method of claim 10, wherein R² and R⁴ are each hydrogens, and the compound has a structure represented by Formula (Ia):

14. The method of claim 13 wherein R¹ is methyl and R³ is hydrogen.

15. The method of claim 13 wherein R¹ is hydrogen and R³ is methyl.

16. The method of claim 13 wherein R¹ is methyl and R³ is methyl.

17. The method of claim 10 wherein the disease characterized by TDP-43 proteinopathy is amyotrophic lateral sclerosis, Alzheimer'"'"'s disease, Parkinson'"'"'s disease, or frontotemporal lobar degeneration.