Aminoalcohol lipidoids and uses thereof
Aminoalcohol lipidoids are prepared by reacting an amine with an epoxide-terminated compound are described. Methods of preparing aminoalcohol lipidoids from commercially available starting materials are also provided. Aminoalcohol lipidoids may be prepared from racemic or stereochemically pure epoxides. Aminoalcohol lipidoids or salts forms thereof are preferably biodegradable and biocompatible and may be used in a variety of drug delivery systems. Given the amino moiety of these aminoalcohol lipidoid compounds, they are particularly suited for the delivery of polynucleotides. Complexes, micelles, liposomes or particles containing the inventive lipidoids and polynucleotide have been prepared. The inventive lipidoids may also be used in preparing microparticles for drug delivery. They are particularly useful in delivering labile agents given their ability to buffer the pH of their surroundings.
1. A compound of formula:
wherein:
A is substituted or unsubstituted, branched or unbranched, acyclic C 2-20 alkylene, wherein the alkylene is interrupted by 1 or more heteroatoms independently selected from O, S and N;
one occurrence of R 1 is substituted or unsubstituted, branched or unbranched, C 2-20 -aliphatic, and the other occurrence of R 1 is hydrogen; and
R B , R C , and R D are, independently, hydrogen or unsubstituted, branched or unbranched C 1-20 -aliphatic;
or R B and R D together form a cyclic structure;
or R C and R D together form a cyclic structure;
or a pharmaceutically acceptable salt thereof.
2. The compound of claim 1 , wherein R B , R C , and R D are all hydrogen.
3. The compound of claim 1 , wherein R B , R C , and R D are all C 1 -C 6 alkyl.
4. The compound of claim 1 , wherein each of R B , R C , and R D are hydrogen or methyl.
5. The compound of claim 1 , wherein one occurrence of R 1 is selected from the group consisting of:
6. The compound of claim 1 , wherein one occurrence of R 1 is unsubstituted, acyclic, branched or unbranched C 2 -C 20 aliphatic.
7. The compound of claim 1 , wherein one occurrence of R 1 is substituted, acyclic, branched or unbranched C 2 -C 20 aliphatic.
8. The compound of claim 1 , wherein one occurrence of R 1 is substituted or unsubstituted, unbranched C 2 -C 20 aliphatic.
9. The compound of claim 1 , wherein one occurrence of R 1 is fluorinated C 2 -C 20 aliphatic.
10. The compound of claim 1 , wherein one occurrence of R 1 is substituted or unsubstituted, cyclic or acyclic, branched or unbranched C 2-20 alkyl.
11. The compound of claim 1 , wherein one occurrence of R 1 is selected from the group consisting of:
12. The compound of claim 1 , wherein one occurrence of R 1 is substituted or unsubstituted, cyclic or acyclic, branched or unbranched C 2-20 alkenyl.
13. The compound of claim 1 , wherein one occurrence of R 1 is selected from the group consisting of:
14. The compound of claim 1 , wherein one occurrence of R 1 is selected from the group consisting of:
15. The compound of claim 1 , wherein A is unsubstituted, unbranched, acyclic C 2-10 alkylene interrupted by 1 or more oxygen atoms.
16. The compound of claim 1 , wherein A is unsubstituted, unbranched, acyclic C 2-10 alkylene interrupted by 1 or more nitrogen atoms.
17. The compound of claim 1 , wherein A is selected from the group consisting of:
18. The compound of claim 1 , wherein
is
19. The compound of claim 1 , wherein
is
20. The compound of claim 1 , wherein the compound is selected from the group consisting of:
and pharmaceutically acceptable salts thereof.
21. A pharmaceutical composition comprising a compound of claim 1 ; and a pharmaceutical agent.
22. The pharmaceutical composition of claim 21 , wherein the pharmaceutical agent is selected from the groups consisting of polynucleotides, proteins, peptides, and small molecule drugs.
23. The compound of claim 1 , wherein R B , R C , and R D are the same.
24. The pharmaceutical composition of claim 21 , wherein the pharmaceutical agent is DNA or RNA.
25. The pharmaceutical composition of claim 21 , wherein the pharmaceutical agent is dsRNA, siRNA, shRNA, miRNA, antisense RNA, or a polynucleotide that encodes a protein or peptide.