Lipids for delivery of active agents
Compounds are provided having the following structure: Formula (I) or a pharmaceutically acceptable salt, tautomer or stereoisomer thereof, wherein R, R 1 , R 2 , G 1 , G 2 and n are as defined herein. Use of the compounds as a component of lipid nanoparticle formulations for delivery of a therapeutic agent, compositions comprising the compounds and methods for their use and preparation are also provided.
1. A compound having the following structure (I):
or a pharmaceutically acceptable salt or stereoisomer thereof, wherein:
G1 is —OH, —NR 3 R 4 , —(C═O)NR 5 or —NR 3 (C═O)R 5 ;
G2 is —CH 2 — or —(C═O)—;
R 1 and R 2 are each independently optionally substituted C 12 -C 36 alkyl, which is branched and saturated or unsaturated;
R 3 and R 4 are each independently H or optionally substituted C 1 -C 6 alkyl, which is straight or branched and saturated or unsaturated;
R 5 is optionally substituted C 1 -C 6 alkyl, which is straight or branched and saturated or unsaturated; and
n is an integer from 2 to 6.
2. The compound of claim 1 , having the following structure (IA):
wherein
R 6 and R 7 are, at each occurrence, independently H or straight or branched, saturated or unsaturated C 1 -C 14 alkyl;
a and b are each independently an integer ranging from 1 to 15, provided that R 6 and a, and R 7 and b, are each independently selected such that R 1 and R 2 , respectively, are each independently branched, saturated or unsaturated C 12 -C 36 alkyl.
3. The compound of claim 1 , having the following structure (IB):
wherein R 8 , R 9 , R 10 and R 11 are each independently straight or branched, saturated or unsaturated C 4 -C 12 alkyl, provided that R 8 and R 9 , and R 10 and R 11 , are each independently selected such that R 1 and R 2 , respectively, are each independently branched, saturated or unsaturated C 12 -C 36 alkyl.
4. The compound of claim 3 , wherein R 8 , R 9 , R 10 and R 11 are each independently straight or branched, saturated or unsaturated C 6 -C 10 alkyl.
5. The compound of claim 1 , wherein R 1 and R 2 are each independently branched, saturated or unsaturated C 12 -C 20 alkyl.
6. The compound of claim 1 , wherein R 1 and R 2 are each saturated.
7. The compound of claim 1 , wherein R 1 and R 2 have the following structure:
8. The compound of claim 1 , wherein G 1 is —OH.
9. The compound of claim 1 , wherein G 1 is —NR 3 R 4 .
10. The compound of claim 9 , wherein G 1 is —NH 2 , —NHCH 3 or —N(CH 3 ) 2 .
11. The compound of claim 1 , wherein G 1 is —(C═O)NR 5 .
12. The compound of claim 1 , wherein G 1 is —NR 3 (C═O)R 5 .
13. The compound of claim 12 , wherein G 1 is —NH(C═O)CH 3 or —NH(C═O)CH 2 CH 2 CH 3 .
14. The compound of claim 1 , wherein G 2 is —CH 2 —.
15. The compound of claim 1 , wherein G 2 is —(C═O)—.
16. The compound of claim 1 , wherein R 1 , R 2 , R 3 , R 4 and R 5 are each unsubstituted.
17. The compound of claim 1 , having one of the following structures:
18. A composition comprising the compound of claim 1 and a therapeutic agent.
19. A method for administering a therapeutic agent to a patient in need thereof, the method comprising administering the composition of claim 18 to the patient.
20. A lipid nanoparticle comprising the compound of claim 1 and a therapeutic agent.