Withanolides useful for the treatment of neurodegenerative diseases
Provided herein are synthetic analogs of withanolide natural products and their pharmaceutical uses in treating neurodegenerative diseases.
1. A method of treating amyotrophic lateral sclerosis in a patient comprising administering to the patient a therapeutically effective amount of a compound Formula (Ia):
wherein:
R 1 is hydrogen, or methyl; and
R 3 is hydrogen, or methyl,
wherein, R 1 and R 3 cannot both be hydrogen.
2. The method of claim 1 , wherein R 1 is methyl and R 3 is hydrogen.
3. The method of claim 1 , wherein R 1 is hydrogen and R 3 is methyl.
4. The method of claim 1 , wherein R 1 is methyl and R 3 is methyl.
5. A method of administering a compound to a patient, comprising: administering to the patient a compound Formula (Ia):
wherein:
R1 is hydrogen, or methyl; and
R3 is hydrogen, or methyl,
wherein, R1 and R3 cannot both be hydrogen,
wherein the patient is identified as having a disease characterized by a TDP-43 proteinopathy selected from the group consisting of: amyotrophic lateral sclerosis, Alzheimer's disease, Parkinson's disease, and frontotemporal lobar degeneration.
6. The method of claim 5 , wherein R 1 is methyl and R 3 is hydrogen.
7. The method of claim 5 , wherein R 1 is hydrogen and R 3 is methyl.
8. The method of claim 5 , wherein R 1 is methyl and R 3 is methyl.
9. The method of claim 5 , wherein the patient is identified as having amyotrophic lateral sclerosis.