Oligomer-opioid agonist conjugates

• US 8,575,196 B2
• Filed: 07/21/2010
• Issued: 11/05/2013
• 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:
  US13/386,327
• Publication Number:
  US 20120184581A1
• Time in Patent Office: 1,203 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 of Formula II-Cc

2. The compound of claim 1, wherein R_II is lower alkyl.

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

4. The compound of claim 3, wherein R_II″

is hydrogen.

5. The compound of claim 4, wherein X is a covalent bond.

6. The compound of claim 5, wherein R_II′

is hydrogen.

7. The compound of claim 6, wherein Alk is ethylene.

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

9. The compound of claim 8, wherein each poly(alkylene oxide) oligomer is a poly(ethylene glycol) oligomer.

10. The compound of claim 9, wherein each poly(ethylene glycol) oligomer includes an alkoxy or hydroxyl end-capping moiety.

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

12. A dosage form, comprising a compound of claim 1.

13. 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.

14. The composition of claim 1, wherein the composition is suitable for oral administration.

15. A method of treating pain in a patient, comprising administering the composition of claim 11.

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

17. The compound of claim 16, wherein the poly(ethylene oxide) oligomer is made of between 2 and 10 monomers.