Opioid ketal compounds and uses thereof

1. A method of treating or ameliorating pain in a mammal identified as in need thereof, by providing an extended release of a parent opioid to the mammal, wherein said method comprises orally administering to the mammal an effective amount of one or more compounds of Formula I:

or a pharmaceutically acceptable salt thereof,

wherein

R 1 is H or CH 3 ,

R 2 is H,

n is 0, 1, 2 or 3,

R 3 and R 4 are independently H or optionally substituted C 1 -C 4 alkyl, or when n is 0, then

R 3 and R 4 and the carbon atoms to which they are attached together form a five, six, or seven membered ring, which is optionally mono or disubstituted by C 1 -C 4 alkyl;

and wherein when R 3 and R 4 are, independently, optionally substituted C 1 -C 4 alkyl, the carbon atoms labeled * and ** are independently in the R or S configuration;

wherein said one or more compounds of Formula I are hydrolyzed after the oral administration to provide said extended release of the parent opioid to the mammal.

2. The method according to claim 1 , wherein R 1 is CH 3 , R 2 is H, n is 1, and R 3 and R 4 are each CH 3 in the one or more compounds of Formula I, or a pharmaceutically acceptable salt thereof.

3. The method according to claim 1 , wherein R 1 is CH 3 , R 2 is H, n is 2, and R 3 and R 4 are each CH 3 in the one or more compounds of Formula I, or a pharmaceutically acceptable salt thereof.

4. The method according to claim 1 , wherein R 1 is H, R 2 is H, n is 1, and R 3 and R 4 are each CH 3 in the one or more compounds of Formula I, or a pharmaceutically acceptable salt thereof.

5. The method according to claim 1 , wherein R 1 is CH 3 , R 2 is H, n is 0, and R 3 and R 4 together with the carbon atoms to which they are attached form a six-membered carbon ring.

6. The method according to claim 1 , wherein said parent opioid is hydrocodone or hydromorphone.

7. The method according to claim 1 , wherein said one or more compounds of Formula I are hydrolyzed in gastrointestinal tract of the mammal.

8. A method of decreasing abuse potential of a parent opioid in a mammal identified as in need of an opioid therapy, comprising orally administering to the mammal an effective amount of one or more compounds of Formula I:

or a pharmaceutically acceptable salt thereof,

wherein

R 1 is H or CH 3 ,

R 2 is H,

n is 0, 1, 2 or 3,

R 3 and R 4 are independently H or optionally substituted C 1 -C 4 alkyl, or when n is 0, then

R 3 and R 4 and the carbon atoms to which they are attached together form a five, six, or seven membered ring, which is optionally mono or disubstituted by C 1 -C 4 alkyl;

and wherein when R 3 and R 4 are, independently, optionally substituted C 1 -C 4 alkyl, the carbon atoms labeled * and ** are independently in the R or S configuration,

wherein the method provides an extended release of the parent opioid, as compared to a direct oral administration of the parent opioid or a pharmaceutically acceptable salt thereof in an immediate release form.

9. The method according to claim 8 , wherein R 1 is CH 3 , R 2 is H, n is 1, and R 3 and R 4 are each CH 3 in the one or more compounds of Formula I, or a pharmaceutically acceptable salt thereof.

10. The method according to claim 8 , wherein R 1 is CH 3 , R 2 is H, n is 2, and R 3 and R 4 are each CH 3 in the one or more compounds of Formula I, or a pharmaceutically acceptable salt thereof.

11. The method according to claim 8 , wherein R 1 is H, R 2 is H, n is 1, and R 3 and R 4 are each CH 3 in the one or more compounds of Formula I, or a pharmaceutically acceptable salt thereof.

12. The method according to claim 8 , wherein R 1 is CH 3 , R 2 is H, n is 0, and R 3 and R 4 together with the carbon atoms to which they are attached form a six-membered carbon ring.

13. The method according to claim 8 , wherein said parent opioid is hydrocodone or a hydromorphone.

14. The method according to claim 8 , wherein said method reduces euphoric effects otherwise produced by said parent opioid.