Opioid ketal compounds and uses thereof
This invention relates to opioid ketal compounds of Formula (I), Formula (II), or Formula (III): or a pharmaceutically acceptable salts thereof, wherein R 1 is H or CH 3 , R 2 is H or OH, 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 six, or seven membered ring, which is optionally mono or disubstituted by C 1 -C 4 alkyl. The invention also relates to oxycodone ketal compounds of Formula (IV) or (V): or a pharmaceutically acceptable salts thereof. The invention also relates to the use of such compounds for the treatment, prevention, or amelioration of pain.
1. A method of treating or ameliorating pain in a mammal identified as in need thereof through an oxycodone therapy, comprising orally administering to the mammal an effective amount of one or more compounds of Formula II, III, or V:
or a pharmaceutically acceptable salt thereof, wherein the carbon atom labeled * or ** is in R or S configuration, and
wherein the method provides the mammal an extended release of the oxycodone, as compared to an oral administration of the oxycodone or a pharmaceutically acceptable salt thereof in an immediate release form to the mammal.
2. The method of claim 1 , wherein the pain is acute pain or chronic pain.
3. The method of claim 1 , wherein the method comprises the administration of an effective amount of a compound of Formula V selected from the group consisting of
or a pharmaceutically acceptable salt thereof.
4. The method of claim 3 , wherein the method comprises administering to the mammal a mixture of two or more compounds of Formula V or pharmaceutically acceptable salts thereof.
5. The method of claim 3 , wherein the method comprises administering to the mammal a mixture comprising compounds VA, VB, VC, and VD, or pharmaceutically acceptable salts thereof.
6. The method of claim 1 , wherein the method comprises the administration of an effective amount of one or more compounds of Formula II or Formula III:
or a pharmaceutically acceptable salt thereof.
7. The method of claim 6 , wherein the method comprises the administration of a mixture comprising two or more stereoisomers of a compound of Formula III, or pharmaceutically acceptable salts thereof.
8. The method of claim 1 , wherein the method reduces an abuse or misuse potential of the oxycodone therapy.
9. The method of claim 1 , wherein the method reduces euphoric effects of the oxycodone therapy.
10. The method of claim 1 , wherein the compound of Formula II, III, or V is administered at a dose of from 0.1 to 5 mg/kg, or a molar equivalent amount of a pharmaceutically acceptable salt thereof, based on the body weight of the mammal.
11. The method of claim 1 , wherein the compound of Formula II, III, or V, or a pharmaceutically acceptable salt thereof, is administered as part of a pharmaceutical composition comprising between 5 mg and 320 mg of the compound of Formula II, III, or V or a molar equivalent of the pharmaceutically acceptable salt thereof.