Amphiphilic macromolecules and methods of use thereof

Patent metadata

Field	Value
Publication number	US-9630905-B2
Application number	US-201514847986-A
Country	US
Kind code	B2
Filing date	Sep 8, 2015
Priority date	Sep 8, 2014
Publication date	Apr 25, 2017
Grant date	Apr 25, 2017

Abstract

Certain embodiments of the invention provide a compound of formula (I):

A-X—Y—Z—R 1   (I),

or a salt thereof, wherein A, X, Y, Z and R 1 have any of the values defined in the specification, and methods of use thereof. For example, certain embodiments of the invention provide a method for inhibiting atherosclerosis or atherosclerotic development in a mammal, comprising administering to the mammal an effective amount of a compound of formula (I), or a pharmaceutically acceptable salt thereof.

First claim

What is claimed is:

1. A compound of formula (I):
A-X—Y—Z—R 1   (I),

or a salt thereof, wherein:
A is a carboxy group;
X is a straight chain or branched chain aliphatic group containing from 2 carbons to about 10 carbons, wherein the aliphatic group is substituted with 1 or more groups independently selected from —OR a , and —NR b R c ; wherein R a is independently selected from a —(C 1 -C 20 )alkyl, —(C 2 -C 20 )alkenyl and —(C 2 -C 20 )alkynyl; wherein R b is independently H or (C 1 -C 6 )alkyl; and wherein R c is independently selected from a —(C 1 -C 20 )alkyl, —(C 2 -C 20 )alkenyl and —(C 2 -C 20 )alkynyl;
Y is —C(═O);
Z is O or NH; and
R 1 is a poly(alkylene oxide) having between about 2 and about 150 repeating units.

2. The compound of claim 1 , wherein the aliphatic group is substituted with 1 or more —OR a groups.

3. The compound of claim 1 , wherein the aliphatic group is substituted with 1 or more —NR b R c groups.

4. The compound of claim 1 , wherein Z is O.

5. The compound of claim 1 , wherein R 1 is:

wherein n is about 2 to about 150.

6. The compound of claim 1 , selected from:

7. A composition comprising a plurality of compounds of formula (I) as described in claim 1 , in a solvent.

8. An aggregate structure comprising a plurality of compounds of formula (I), as described in claim 1 , and a solvent.

9. A method for preparing an aggregate structure, comprising combining a plurality of compounds of formula (I), as described in claim 1 , in a solvent; and allowing them to form the aggregate structure.

10. An encapsulate comprising a molecule surrounded or partially surrounded by a plurality of compounds of formula (I), as described in claim 1 .

11. A method for preparing an encapsulate, comprising combining a) a plurality of compounds of formula (I), as described in claim 1 ; b) a molecule; and c) a solvent; and allowing the compounds of formula (I) to aggregate around the molecule, to provide the encapsulate.

12. A pharmaceutical composition comprising a compound of formula (I), as described in claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

13. A pharmaceutical composition comprising an encapsulate, as described in claim 10 , and a pharmaceutically acceptable carrier.

14. A method for inhibiting oxLDL uptake by a cell, comprising contacting the cell in vitro or in vivo with a compound of formula (I), as described in claim 1 , or a pharmaceutically acceptable salt thereof.

15. A method of preventing foam cell formation and/or for inhibiting atherosclerosis or atherosclerotic development in a mammal, comprising administering to the mammal an effective amount of a compound of formula (I), as described in claim 1 , or a pharmaceutically acceptable salt thereof.

16. A method for preparing a compound of formula (I) as described in claim 1 :
A-X—Y—Z—R 1   (I),

wherein Z is O, comprising esterifying a corresponding compound of formula (Ia):
A-X—Y—Z—R 1′   (Ia)

wherein R 1′ is H with a hydroxyl polyether residue to provide the compound of formula (I).

17. The compound of claim 1 , wherein X is a straight chain or branched chain aliphatic group containing from 2 carbons to 4 carbons, wherein the aliphatic group is substituted with 1 or more —OR a groups.

18. The compound of claim 1 , wherein R a is —(C 6 -C 14 )alkyl.

19. The compound of claim 5 , wherein n is about 110 to about 120.

20. The compound of claim 1 , which is:

Assignees

• Univ Rutgers

Inventors

• Uhrich Kathryn E
• Moghe Prabhas
• Abdelhamid Dalia
• Gu Li
• Zhang Yingyue

Classifications

• C07C69/708 Primary

  Ethers · CPC title

• C08G65/3322

  acyclic · CPC title