Multifunctional cytoprotectant for treatment of pathogenic processes mediated by oxidative stress and toxic electrophiles

1 . A method of treating a toxicity due to a therapeutic agent or an agent that causes oxidative cellular damage in a subject receiving the agent, the method comprising administering to the subject a compound of formula (I)

or a tautomer thereof; or a geometric or optical isomer thereof; or racemate thereof; or a pharmaceutically acceptable salt thereof, in an amount effective to reduce the toxicity due to the agent,

wherein:

R 1 and R 3 are independently alkyl, alkenyl, aryl, aralkyl, cycloalkyl, heteroaryl, heteroaralkyl or heterocycloalkyl;

R 2 is NH 2 , NHCOR 3 , NH-alkyl, N,N-dialkyl, cyclic N,N-di alkyl, SH, S-alkyl, S-aryl, aryl, heteroaryl, or NR 4 R 5 ; and

R 4 and R 5 are independently alkyl or NH-alkyl, or R 4 and R 5 can form a ring with each other, and any ring so formed is heteroaromatic, and any ring so formed may contain one or more N, O and/or S atoms;

wherein any aryl, aralkyl, cycloalkyl, heteroaryl, heteroaralkyl, or heterocycloalkyl ring can be independently substituted with ═O, OH, halogen, CH 3 or NH 2 ; and

wherein any alkyl can independently be branched or unbranched.

2 . The method of claim 1 , wherein the therapeutic agent is acetaminophen, diclofenac, cyclophosphamide, valproic acid, clopidogrel, esomeprazole, atorvastatin, duloxetine, raloxifene, a platinum containing antineoplatstic agent, or radiation used in radiation therapy.

3 . The method of claim 2 , wherein the platinum containing antineoplatstic agent is cisplatin.

4 . The method of claim 1 , wherein the agent that causes oxidative cellular damage is tobacco smoke, acrolein, alcohol, or a radiocontrast agent.

5 . The method of claim 1 , wherein the agent is a polarizable electrophile.

6 . The method of claim 1 , wherein the toxicity is hepatotoxicity, neurotoxicity, or toxicity due to oxidative cellular stress.

7 . The method of claim 1 , wherein the compound of formula (I) and the agent are administered to the subject at the same time.

8 . The method of claim 7 , wherein the compound of formula (I) and the agent are administered in the same formulation.

9 . The method of claim 1 , wherein the compound of formula (I) is administered to the subject before administration of the agent to the subject.

10 . The method of claim 1 , wherein the compound of formula (I) is administered to the subject after administration of the agent to the subject.

11 . The method of claim 1 , wherein the compound of formula (I) is administered by parenteral administration.

12 . The method of claim 1 , wherein the compound of formula (I) is formulated with an enteric coating and the compound is administered orally.

13 . The method of claim 1 , wherein the compound of formula (I) prevents or reduces hepatotoxicity.

14 . The method of claim 1 , wherein:

R 1 is alkyl, cycloalkyl, or

R 2 is NH 2 , NHCOR 3 , NH-alkyl, SH, S-alkyl, S-aryl or

wherein R 6 is hydrogen or alkyl.

15 . The method of claim 1 , wherein the compound of formula (I) is:

or a tautomer thereof; or a geometric or optical isomer thereof; or racemate thereof; or a pharmaceutically acceptable salt thereof.