Oligomer-opioid agonist conjugates

• US 9,827,239 B2
• Filed: 11/02/2016
• Issued: 11/28/2017
• 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:
  US15/341,470
• Publication Number:
  US 20170112826A1
• Time in Patent Office: 391 Days
• Field of Search: 546 44, 546 45, 514282
• 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. An opioid agonist compound according to Formula I-Ca:

2. The compound of claim 1, wherein POLY possess from about 1 to about 10 monomers.

3. The compound of claim 1, wherein POLY possess 1 monomer.

4. The compound of claim 1, wherein POLY possess 2 monomers.

5. The compound of claim 1, wherein POLY possess 3 monomers.

6. The compound of claim 1, wherein POLY possess 4 monomers.

7. The compound of claim 1, wherein POLY possess 5 monomers.

8. The compound of claim 1, wherein POLY possess 6 monomers.

9. The compound of claim 1, wherein POLY possess 7 monomers.

10. The compound of claim 1, wherein POLY possess 8 monomers.

11. The compound of claim 1, wherein POLY possess 9 monomers.

12. The compound of claim 1, wherein POLY possess 10 monomers.

13. The compound of claim 1, wherein POLY is a methoxy end-capped poly(ethylene oxide).

14. A composition comprising:

(i) a compound of claim 1; and

(ii) optionally, a pharmaceutically acceptable excipient.

15. A dosage form comprising a compound of claim 1.

16. A method of treating pain comprising administering a compound of claim 1 to a patient in need thereof.

17. The compound of claim 1, wherein X is a single bond, —

O—

, or —

OC(O)CH₂O—

.

18. The compound of claim 1 according to either of the following formulas: