Fluoroalkyl, fluoroalkoxy, phenoxy, heteroaryloxy, alkoxy, and amine 1,4-benzoquinone derivatives for treatment of oxidative stress disorders
View Patent ↗Disclosed herein are compounds and methods of using such compounds for treating or suppressing oxidative stress disorders, including mitochondrial disorders, impaired energy processing disorders, neurodegenerative diseases and diseases of aging, or for modulating one or more energy biomarkers, normalizing one or more energy biomarkers, or enhancing one or more energy biomarkers, wherein the compounds are tocopherol quinone derivatives. Further disclosed are compounds, compositions, and methods for treatment of, or prophylaxis against, radiation exposure.
1. A compound of the formula I:
or the hydroquinone form thereof;
wherein:
R 1 and R 2 are independently C 1 -C 10 alkyl;
R 3 is C 1 -C 6 alkyl;
R 4 is C 1 -C 12 n-alkyl and R 5 is —OCH 3 , —OCF 3 , or —OCH 2 CF 3 , wherein R 5 is attached to R 4 at any chemically possible location on the C 1 -C 12 n-alkyl group; or
R 4 is C 6 -C 12 alkyl and R 5 is —CF 3 , wherein R 5 is attached to R 4 at any chemically possible location on the C 6 -C 12 alkyl group;
or a salt, a stereoisomer, or mixture of stereoisomers thereof;
with the proviso that the compound is not
2. The compound of claim 1 , wherein the compound is a quinone.
3. The compound of claim 1 , wherein the compound is a hydroquinone.
4. The compound of claim 1 , wherein R 1 and R 2 are methyl.
5. The compound of claim 1 , wherein R 3 is C 1 -C 4 alkyl.
6. The compound of claim 1 , wherein R 3 is methyl.
7. The compound of claim 1 , wherein R 3 is isopropyl.
8. The compound of claim 1 , wherein R 5 is —CF 3 .
9. The compound of claim 1 , wherein R 5 is —OCH 3 .
10. The compound of claim 1 , wherein R 5 is —OCF 3 .
11. The compound of claim 1 , wherein R 5 is —OCH 2 CF 3 .
12. The compound of claim 1 , wherein R 4 is C 6 -C 12 alkyl for all values of R 5 .
13. The compound of claim 1 , wherein R 4 is a n-alkyl for all values of R 5 .
14. The compound of claim 13 , wherein R 4 is C 6 alkyl.
15. The compound of claim 13 , wherein R 4 is C 9 alkyl.
16. The compound of claim 13 , wherein R 4 is C 10 alkyl.
17. The compound of claim 13 , wherein R 4 is C 11 alkyl.
18. The compound of claim 1 , wherein the compound is selected from the group consisting of:
and the hydroquinone forms thereof.
19. The compound of claim 1 , wherein the compound is:
or the hydroquinone form thereof.
20. The compound of claim 1 , wherein the compound is:
or the hydroquinone form thereof.
21. The compound of claim 1 , wherein the compound is:
22. A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier, wherein the compound is not a salt.
23. A pharmaceutical composition comprising a compound of claim 20 and a pharmaceutically acceptable carrier.