Opioid ketal compounds and uses thereof

Patent metadata

Field	Value
Publication number	US-11130765-B2
Application number	US-202016860316-A
Country	US
Kind code	B2
Filing date	Apr 28, 2020
Priority date	May 24, 2013
Publication date	Sep 28, 2021
Grant date	Sep 28, 2021

Abstract

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.

First claim

What is claimed is:

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.

Assignees

• Rhodes Tech

Inventors

• Kupper Robert J
• Glowaky Raymond C

Classifications

• C07D491/20

  Spiro-condensed systems · CPC title

• C07D489/08 Primary

  Oxygen atom · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• C07D489/09

  containing 4aH-8, 9 c-Iminoethano- phenanthro [4, 5-b, c, d] furan ring systems condensed with carbocyclic rings or ring systems · CPC title