Dendritic Molecular Intracellular Transporters and Methods of Making and Using Same

• US 20150315174A1
• Filed: 03/03/2015
• Published: 11/05/2015
• Est. Priority Date: 08/23/2006
• Status: Abandoned Application

• Current Assignee: Vanderbilt University
• Original Assignee: Vanderbilt University
• Inventors: Harth, Eva M., Crowe, James E. Jr., Hamilton, Sharon K., Hamm, Heidi E., Voss, Bryan, Huang, Kui
• Application Number:
  US14/637,105
• Publication Number:
  US 20150315174A1
• Time in Patent Office: Days
• US Class Current: 1/1
• 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 comprising the structure:

2. The compound of claim 1, comprising the structure:

3. The compound of claim 2, comprising the structure:

4. The compound of claim 2, comprising the structure:

15. A method of intracellular delivery comprising administering an effective amount of a compound of claim 1 to a subject.

16. A pharmaceutical composition comprising a therapeutically effective amount of one or more compounds of claim 1 and a pharmaceutically acceptable carrier for administration in a mammal.

5. A method of preparing a compound having the structure:

6. The method of claim 5, further comprising the step of transforming Y into an amine to provide a compound comprising the structure:

7. The method of claim 5, further comprising the step of acylating the amine with a compound comprising the structure:

8. The method of claim 5, further comprising the step of acylating the amine with a compound comprising the structure:

9. The method of claim 8, wherein the thiol protecting group comprises the structure:

10. The product of the method of claim 5.

11. An intracellular delivery composition comprising the general structure:

P-L-B—

F,

wherein P is payload moiety;

wherein L is a linking moiety comprising the structure;

12. The composition of claim 11, comprising at least six guanidinium residues.

13. The composition of claim 11, wherein the payload moiety comprises a luminescent group, a biologically-active group, or a pharmaceutically-active group.

14. The composition of claim 11, wherein L-B—

F comprises the structure;

17. A block copolymer comprising the structure A-B,

wherein A is an oligomeric block comprising at least two reactive residues, and

wherein B is a block comprising at least one functional moiety.

18. The block copolymer of claim 17, wherein the functional moiety comprises a semiconducting moiety, an imaging moiety, or a drug-delivery moiety.

19. A method of nanoparticle formation comprising the steps of:

a. providing a reactor capable of imparting a stimulus and

b. adding to the reactor a block copolymer comprising at least two reactive residues, thereby imparting the stimulus on at least a portion of the block copolymer;

wherein the at least two reactive residues form reactive intermediates upon exposure to the stimulus, and

wherein the reactive intermediates are capable of undergoing a bond-forming reaction.

20. The product of the method of claim 19.