Dendritic molecular intracellular transporters and methods of making and using same

• US 8,969,622 B2
• Filed: 08/23/2007
• Issued: 03/03/2015
• Est. Priority Date: 08/23/2006
• Status: Active Grant

• Current Assignee: Vanderbilt University
• Original Assignee: Vanderbilt University
• Inventors: Harth, Eva M., Crowe, James E. Jr., Huang, Kui, Hamilton, Sharon K., Hamm, Heidi E., Voss, Bryan
• Primary Examiner(s): Switzer, Juliet
• Assistant Examiner(s): HELM, CARALYNNE E
• Application Number:
  US11/844,353
• Publication Number:
  US 20080221043A1
• Time in Patent Office: 2,749 Days
• Field of Search: None
• US Class Current: 564/236
• CPC Class Codes: A61K 47/22 Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
• CPC Class Codes: A61K 47/50 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
• CPC Class Codes: A61K 47/56 the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
• CPC Class Codes: A61K 49/0052 Small organic molecules oligomers, polymers, dendrimers A61K49/0054
• CPC Class Codes: A61K 49/0054 Macromolecular compounds, i.e. oligomers, polymers, dendrimers
• CPC Class Codes: C07D 249/04 1,2,3-Triazoles; Hydrogenated 1,2,3-triazoles
• CPC Class Codes: C07D 311/90 with hydrocarbon radicals, substituted by amino radicals, directly attached in position 9
• CPC Class Codes: C07D 401/14 containing three or more hetero rings
• CPC Class Codes: C08F 293/00 Macromolecular compounds obtained by polymerisation on to a macromolecule having groups capable of inducing the formation of new polymer chains bound exclusively at one or both ends of the starting macromolecule on to polymers modified by introduction of unsaturated end groups C08F290/02
• CPC Class Codes: Y10S 977/754 Dendrimer, i.e. serially branching or "tree-like" structure
• CPC Class Codes: Y10T 436/13 Tracers or tags

Abstract

In accordance with the purpose(s) of the invention, as embodied and broadly described herein, the invention, in one aspect, relates to compounds comprising the structure:

and at least one guanidinium residue, wherein m is zero or a positive integer. Also disclosed are methods of preparing the disclosed compounds. Also disclosed are methods of intracellular delivery comprising administering the disclosed compounds and compositions to a subject. Also disclosed are pharmaceutical compositions comprising a therapeutically effective amount of one or more compounds or compositions of the invention and a pharmaceutically acceptable carrier. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

Claims

1. A compound having the structure:

3. A pharmaceutical composition comprising the compound of claim 1 and a pharmaceutically acceptable carrier for administration in a mammal.

2. A compound having the structure:

4. A pharmaceutical composition comprising the compound of claim 2 and a pharmaceutically acceptable carrier for administration in a mammal.

5. The compound of claim 2, wherein R¹ is hydrogen, and wherein R² comprises a linking moiety of the structure:

6. The compound of claim 5, wherein the payload moiety is a luminescent group, a biologically-active group, or a pharmaceutically-active group.

7. The compound of claim 2, wherein all of R⁷ are hydrogen.

8. The compound of claim 2, wherein R¹, R², and the intermediate nitrogen form a luminescent group comprising the structure:

9. The compound of claim 2, wherein R¹ is hydrogen, and wherein R² is a luminescent group selected from a dansyl group, a coumarin group, a fluorescein isothiocyanate (FITC) group, a 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) group, a catechol group, and a diethylene triamine pentaacetic acid (DTPA) group.

10. The compound of claim 2, wherein R¹ is hydrogen, and wherein R² is a biologically-active group selected from an oligonucleotide, a plasmid DNA, a protein, an immunoglobulin, an antisense oligoDNA, a peptide nucleic acid (PNA), and a peptide.

11. The compound of claim 2, wherein R¹ is hydrogen, and wherein R² is a biologically-active group.

12. The compound of claim 2, wherein R¹ is hydrogen, and wherein R² is a pharmaceutically-active group selected from a drug, a protein, a peptide, a hydrogel, a dendrimer, and a hyperbranched polymeric structure.

13. The compound of claim 2, wherein R¹ is hydrogen, and wherein R² is a pharmaceutically-active group.

15. The compound of claim 11, wherein n is 5, and wherein all of R⁷ are hydrogen.

14. A compound having the structure: