Oligomer-opioid agonist conjugates

• US 8,569,343 B2
• Filed: 06/29/2012
• Issued: 10/29/2013
• Est. Priority Date: 03/12/2007
• Status: Active Grant

• Current Assignee: Nektar Therapeutics
• Original Assignee: Nektar Therapeutics
• Inventors: Riggs-Sauthier, Jennifer, Deng, Bo-Liang, Riley, Timothy A.
• Primary Examiner(s): Aulakh, Charanjit
• Application Number:
  US13/538,540
• Publication Number:
  US 20120289548A1
• Time in Patent Office: 487 Days
• Field of Search: 514/329, 546/224
• US Class Current: 514/329
• CPC Class Codes: A61K 31/402 1-aryl substituted, e.g. piretanide
• CPC Class Codes: A61K 31/4025 not condensed and containing further heterocyclic rings, e.g. cromakalim
• 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 31/4468 having a nitrogen directly attached in position 4, e.g. clebopride, fentanyl
• CPC Class Codes: A61K 31/485 Morphinan derivatives, e.g. morphine, codeine
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/60 the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: C07D 489/02 with oxygen atoms attached in positions 3 and 6, e.g. morphine, morphinone

Abstract

The invention provides compounds that are chemically modified by covalent attachment of a water-soluble oligomer. A compound of the invention, when administered by any of a number of administration routes, exhibits characteristics that are different from those of the compound not attached to the water-soluble oligomer.

Claims

1. A compound selected from a compound of Formula II-Cb

2. The compound of claim 1, wherein Alk is ethylene.

3. The compound of claim 2, wherein R_II is lower alkyl.

4. The compound of claim 2, wherein R_II is ethyl.

5. The compound of claim 3, wherein R_II′

is hydrogen.

6. The compound of claim 5, wherein R_II″

is hydrogen.

7. The compound of claim 6, wherein Ar is phenyl.

8. The compound of claim 7, wherein the poly(alkylene oxide) is poly(ethylene oxide).

9. The compound of claim 8, wherein the poly(ethylene oxide) includes an alkoxy or hydroxyl end-capping moiety.

10. The compound of claim 9, wherein the poly(ethylene oxide) is made of between 2 and 30 monomers.

11. The compound of claim 10, wherein the poly(ethylene oxide) is made of between 2 and 10 monomers.

16. A composition comprising a compound of claim 1, and optionally, a pharmaceutically acceptable excipient.

17. The composition of claim 16, wherein the composition is suitable for oral administration.

18. A composition of matter comprising a compound of claim 1, wherein the compound is present in a dosage form.

19. A method of treating pain in a patient, comprising administering a therapeutically effective amount of a compound of claim 1 to the patient in need thereof.

20. A method of treating pain in a patient, comprising administering the composition of claim 16 to the patient in need thereof.

12. A compound selected from a compound of the formula

13. The compound of claim 12, wherein n is an integer from 1 to 10.

21. A composition comprising a compound of claim 12, and optionally, a pharmaceutically acceptable excipient.

22. The composition of claim 21, wherein the composition is suitable for oral administration.

23. A composition of matter comprising a compound of claim 12, wherein the compound is present in a dosage form.

24. A method of treating pain in a patient, comprising administering a therapeutically effective amount of a compound of claim 12 to the patient in need thereof.

25. A method of treating pain in a patient, comprising administering the composition of claim 21 to the patient in need thereof.

14. A compound selected from a compound of the formula

15. The compound of claim 14, wherein n is an integer from 1 to 10.

26. A composition comprising a compound of claim 14, and optionally, a pharmaceutically acceptable excipient.

27. The composition of claim 26, wherein the composition is suitable for oral administration.

28. A composition of matter comprising a compound of claim 14, wherein the compound is present in a dosage form.

29. A method of treating pain in a patient, comprising administering a therapeutically effective amount of a compound of claim 14 to the patient in need thereof.

30. A method of treating pain in a patient, comprising administering the composition of claim 26 to the patient in need thereof.