Methods and compositions for treating conditions mediated by oxidative stress or electrophilic environmental toxins

1. A method of treating a subject with a disease or tissue injury mediated by cellular oxidative stress, wherein the disease or tissue injury is atherosclerosis, diabetes, Alzheimer's disease, stroke or traumatic spinal cord injury, the method comprising administering to the subject a therapeutically effective amount of a compound of formula (I)

wherein

R 1 and R 2 are independently H, alkyl, alkoxy alkyl, acyloxy alkyl, aryl, aryloxy, acyloxy aryl, heteroaryl, heteroaryloxy, or acyloxy heteroaryl;

X is COR 3 , CO 2 R 3 , NO 2 , CN, CON(R 3 ) 2 , or SO 2 R 3 ;

R 3 is H, alkyl, alkoxy alkyl, acyloxy alkyl, aryl, aryloxy, acyloxy aryl, heteroaryl, heteroaryloxy, acyloxy heteroaryl, or trifluoromethyl; and/or

R 2 forms a ring together with either R 1 or R 3 , or R 2 forms rings with both R 1 and R 3 ;

wherein any ring formed between R 2 with R 1 and/or R 3 optionally and independently contains one or more O, S, N or substituted N, where substitution at N is an alkyl or acyl group;

wherein any alkyl can independently be branched or unbranched;

wherein any aryl or heteroaryl can independently be optionally substituted with —CH3, —NH2, —OH, ═O, halogen, alkyl, alkoxy, acyloxy, aryl and/or acyloxyaryl;

or a tautomer thereof; or a geometric or optical isomer thereof; or racemate thereof;

or a pharmaceutically acceptable salt thereof.

2. The method of claim 1 , wherein the compound has the structure

3. The method of claim 1 , wherein any ring formed between R 2 with R 1 and/or R 3 is independently a 4-12 member ring.

4. The method of claim 3 , wherein any ring formed between R 2 with R 1 and/or R 3 is independently a 5-6 member ring.

5. The method of claim 1 , wherein any ring formed between R 2 with R 1 and/or R 3 independently contains one or more O, S, N or substituted N, where substitution at N is an alkyl or acyl group.

6. The method of claim 1 , wherein any alkyl is independently C1-C6 alkyl.

7. The method of claim 6 , wherein any alkyl is independently C1-C3 alkyl.

8. The method of claim 1 , wherein the compound has the structure

wherein R 4 ═H, alkyl, alkoxy, acyloxy, aryl or acyloxyaryl; or a tautomer thereof.

9. The method of claim 1 , wherein the compound has the structure

10. The method of claim 1 , wherein the compound reduces hepatotoxicity.

11. A method of providing a nutritional supplement to a subject comprising administering to the subject a compound of formula (I)

wherein

R 1 and R 2 are independently H, alkyl, alkoxy alkyl, acyloxy alkyl, aryl, aryloxy, acyloxy aryl, heteroaryl, heteroaryloxy, or acyloxy heteroaryl;

X is COR 3 , CO 2 R 3 , NO 2 , CN, CON(R 3 ) 2 , or SO 2 R 3 ;

R 3 is H, alkyl, alkoxy alkyl, acyloxy alkyl, or trifluoromethyl; and/or

R 2 forms a ring together with either R 1 or R 3 , or R 2 forms rings with both R 1 and R 3 ; wherein any ring formed between R 2 with R 1 and/or R 3 optionally and independently contains one or more O, S, N or substituted N, where substitution at N is an alkyl or acyl group;

wherein any alkyl can independently be branched or unbranched;

wherein any aryl or heteroaryl can independently be optionally substituted with —CH3, —NH2, —OH, ═O, halogen, alkyl, alkoxy, acyloxy, aryl and/or acyloxyaryl;

or a tautomer thereof; or a geometric or optical isomer thereof; or racemate thereof;

or a pharmaceutically acceptable salt thereof.

12. The method of claim 11 , wherein the compound has the structure

wherein R 4 ═H, alkyl, alkoxy, acyloxy, aryl or acyloxyaryl; or a tautomer thereof.

13. A method of treating the skin of a subject comprising administering to the skin of the subject a compound of formula (I)

wherein

R 1 is H, alkyl, alkoxy alkyl, or acyloxy alkyl;

R 2 is H, alkyl, alkoxy alkyl, acyloxy alkyl, aryl, aryloxy, acyloxy aryl, heteroaryl, heteroaryloxy, or acyloxy heteroaryl;

X is COR 3 , CO 2 R 3 , NO 2 , CN, CON(R 3 ) 2 , or SO 2 R 3 ;

R 3 is H, alkyl, alkoxy alkyl, acyloxy alkyl, or trifluoromethyl; and/or

R 2 forms a ring together with either R 1 or R 3 , or R 2 forms rings with both R 1 and R 3 ; wherein any ring formed between R 2 with R 1 and/or R 3 optionally and independently contains one or more O, S, N or substituted N, where substitution at N is an alkyl or acyl group;

wherein any alkyl can independently be branched or unbranched;

wherein any aryl or heteroaryl can independently be optionally substituted with —CH3, —NH2, —OH, ═O, halogen, alkyl, alkoxy, acyloxy, aryl and/or acyloxyaryl;

or a tautomer thereof; or a geometric or optical isomer thereof; or racemate thereof;

or a pharmaceutically acceptable salt thereof.

14. The method of claim 13 , wherein the compound is used to treat an aging effect on the skin or to treat sun damage to the skin.

15. The method of claim 14 , wherein the compound is used to treat wrinkles.