Multifunctional small molecules

• US 9,402,911 B2
• Filed: 11/20/2012
• Issued: 08/02/2016
• Est. Priority Date: 12/08/2011
• Status: Expired due to Fees

• Current Assignee: Board of Regents of the University of Michigan (University of Michigan)
• Original Assignee: Board of Regents of the University of Michigan (University of Michigan)
• Inventors: Baker, James R. Jr., Huang, Baohua M., Thomas, Thommey P.
• Primary Examiner(s): DICKINSON, PAUL W
• Application Number:
  US14/363,185
• Publication Number:
  US 20140294733A1
• Time in Patent Office: 1,351 Days
• US Class Current: 1/1
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/519 ortho- or peri-condensed with heterocyclic rings
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 47/54 the modifying agent being an organic compound
• CPC Class Codes: A61K 47/595 Polyamides, e.g. nylon polyamino acids A61K47/62
• CPC Class Codes: A61K 49/10 Organic compounds
• CPC Class Codes: C08G 73/028 Polyamidoamines
• CPC Class Codes: C08G 83/004 After treatment of dendrimers
• CPC Class Codes: C08L 101/005 Dendritic macromolecules

Abstract

The present invention relates to dendrimer synthesis. Specifically, the present invention relates to dendrimer compositions (e.g., scaffolds) capable of copper-free click conjugation for use in the synthesis of functionalized dendrimers, and methods of use of the same.

Claims

1. A composition comprising a generation 5 or higher PAMAM dendrimer conjugated with one or more cyclooctyne moieties.

2. The composition of claim 1, wherein said generation 5 or higher PAMAM dendrimer is conjugated with said one or more cyclooctyne moieties via amide bonds.

3. The composition of claim 1, wherein said cyclooctyne moieties are selected from the group consisting of

4. The composition of claim 1, wherein said cyclooctyne moieties are conjugated with one or more ligands.

5. The composition of claim 4, wherein said one or more ligands are conjugated with azide moieties.

6. The composition of claim 5, wherein said cyclooctyne moieties are connected with said azide moeities via copper-free click chemistry.

7. The composition of claim 4, wherein said one or more ligands are independently selected from the group consisting of a therapeutic agent, a targeting agent, an imaging agent, and a trigger agent.

8. The composition of claim 4, wherein said one or more ligands are methotrexate and folic acid.

9. A method of synthesizing a functionalized dendrimer, said method comprising:

a) providing a generation 5 or higher PAMAM dendrimer having one or more cyclooctyne moieties and a one or more ligands having an azide moiety; and

b) conjugating said generation 5 or higher PAMAM dendrimer with said ligands via copper-free click chemistry between said cyclooctyne moiety and said azide moiety.

10. The method of claim 9, wherein said generation 5 or higher PAMAM dendrimer is conjugated with said one or more cyclooctyne moieties via amide bonds.

11. The method of claim 9, wherein said one or more ligands are selected from the group consisting of a therapeutic agent, a targeting agent, an imaging agent, and a trigger agent.

12. The method of claim 9, wherein said one or more ligands are methotrexate and folic acid.