Oligomer-opioid agonist conjugates

• US 10,143,690 B2
• Filed: 10/24/2017
• Issued: 12/04/2018
• Est. Priority Date: 03/12/2007
• Status: Active Grant

• Current Assignee: Nektar Therapeutics Incorporated
• Original Assignee: Nektar Therapeutics Incorporated
• Inventors: Riggs-Sauthier, Jennifer, Deng, Bo-Liang, Riley, Timothy A.
• Primary Examiner(s): Aulakh, Charanjit
• Application Number:
  US15/791,951
• Publication Number:
  US 20180256563A1
• Time in Patent Office: 406 Days
• Field of Search: 546 44
• 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 method of preparing a compound of the following formula:

2. The method of claim 1, wherein n is 3, 4, 5, 6, 7, or 9.

3. The method of claim 1, wherein the reaction is carried out at a temperature from room temperature to 45°

C.

4. The method of claim 1, wherein the reaction is carried out in a mixture of toluene and DMF.

5. The method of claim 1, wherein the reaction is carried out in the presence of NaH.