Peripheral Opioid Agonists and Peripheral Opioid Antagonists

• US 20130079364A1
• Filed: 04/08/2011
• Published: 03/28/2013
• Est. Priority Date: 04/21/2010
• Status: Abandoned Application

• Current Assignee: Signature Therapeutics, Inc.
• Original Assignee: Signature Therapeutics, Inc.
• Inventors: Jenkins, Thomas E., Husfeld, Craig O.
• Application Number:
  US13/634,532
• Publication Number:
  US 20130079364A1
• Time in Patent Office: Days
• US Class Current: 514/282
• CPC Class Codes: A61K 31/439 the ring forming part of a bridged ring system, e.g. quinuclidine 8-azabicyclo [3.2.1] octanes A61K31/46
• CPC Class Codes: A61K 31/4748 forming part of bridged ring systems strychnine A61K31/475; morphinan derivatives A61K31/485
• CPC Class Codes: C07D 489/02 with oxygen atoms attached in positions 3 and 6, e.g. morphine, morphinone

Abstract

The present disclosure provides compositions, and their methods of use, where the compositions comprise a ketone-modified opioid drug, wherein the drug comprises a ketone-modified opioid and a substituent on the opioid that mediates retention of the drug in the peripheral nervous system as opposed to the central nervous system following ingestion by a subject.

Claims

1. A compound of formula (I):

2. A compound according to claim 1, of formula (II):

3. A compound according to claim 1, of formula (III):

4. A compound according to claim 1, of formula (IV):

10. A method of treating or preventing pain in a patient, which comprises administering an effective amount of a composition comprising the compound of claim 1.

14. A method of treating or preventing an unwanted side effect associated with use of an opioid agonist in a patient, which comprises administering an effective amount of a composition comprising the compound of claim 1.

24. A compound according to claim 1, of the formula:

25. A composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of the compound of claim 1.

30. A method of claim 14, wherein the unwanted side effect is selected from constipation, cough suppression, dry mouth, heartburn, myocardial depression, nausea, pruritus, urinary retention, vomiting, bloating, dry-mouth or heartburn.

5. A compound of formula (V):

6. A compound according to claim 5, of formula (VI):

7. A compound according to claim 5, of formula (VII):

8. A compound according to claim 5, of formula (VIII):

26. A composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of the compound of claim 5.

27. A method of treating or preventing pain in a patient, which comprises administering an effective amount of a composition comprising the compound of claim 5.

28. A method of treating or preventing an unwanted side effect associated with use of an opioid agonist in a patient, which comprises administering an effective amount of a composition comprising the compound of claim 5.

29. A method of claim 28, wherein the unwanted side effect is selected from constipation, cough suppression, dry mouth, heartburn, myocardial depression, nausea, pruritus, urinary retention, vomiting, bloating, dry-mouth or heartburn.

9. (canceled)

11-13. -13. (canceled)

15. (canceled)

16. A compound selected from the group consisting of the formulae:

17-23. -23. (canceled)