Lipids and lipid compositions for the delivery of active agents

1. A compound of formula (I):

wherein:

L is C 1-6 alkylene, *-C 1-4 alkylene-L2-, or *-C 1-4 alkylene-L2-C 1-4 alkylene-, wherein in the * denotes attachment of the moiety to the NR 1 R 2 group;

L2, attached in either direction, is —C(O)O—;

R 1 and R 2 are each independently optionally substituted C 1-6 alkyl, wherein said C 1-6 alkyl is optionally substituted with one or two substituents each independently selected from the group consisting of: OH, C 1-3 alkoxy, COOH, and COO—C 1-4 alkyl,

R 3 and R 4 are each independently chain:

(b) —Z 1 —R b —Z 2 —R a ,

wherein Z 1 , attached in either direction, is each independently —O— or —C(O)O—;

Z 2 , attached in either direction, is —C(O)O—;

R a is C 2-22 alkyl, C 2-22 alkenyl, or C 2-22 alkynyl;

each R b is independently C 1-20 alkylene, C 2-20 alkenylene, or C 2-20 alkynylene;

provided that chain (b) has at least 12 carbon atoms and no more than 30 carbon atoms;

X is CR 6 ; and

R 6 is H, halo, C 1-6 alkyl, or R 4 ; or a pharmaceutically acceptable salt thereof.

2. The compound according to claim 1 wherein R 6 is H, chloro, bromo, or C 1-3 alkyl or a pharmaceutically acceptable salt thereof.

3. The compound according to claim 2 wherein R 6 is H; or a pharmaceutically acceptable salt thereof.

4. The compound according to claim 3 wherein:

L is methylene, ethylene, or propylene, or

L is *-C 1-3 alkylene-OC(O)— or

L is *-C 1-4 alkylene-L2-C 1-2 alkylene-, wherein L2, attached in either direction, is C(O)O; or a pharmaceutically acceptable salt thereof.

5. The compound according claim 4 wherein R 1 and R 2 are each independently optionally substituted methyl or optionally substituted ethyl; or a pharmaceutically acceptable salt thereof.

6. The compound according to claim 3 wherein L-NR 1 R 2 group of formula (I) is selected from the group consisting of:

Structure

wherein the dashed line indicate the point of attachment to formula (I); or a pharmaceutically acceptable salt thereof.

wherein the dashed line indicate the point of attachment to formula (I); or a pharmaceutically acceptable salt thereof.

7. The compound according to claim 6 wherein Z 1 is —O—; R b is C 1-10 alkylene; Z 2 is —OC(O)—; and Ra is C 5-18 alkyl or C 11-18 alkenyl having one to three double bonds; or a pharmaceutically acceptable salt thereof.

8. The compound according to claim 1 wherein R 4 =R 3 ; or a pharmaceutically acceptable salt thereof.

9. The compound according to claim 1 having the following formula:

or a pharmaceutically acceptable salt thereof.

10. The compound according to claim 1 having the following formula:

or a pharmaceutically acceptable salt thereof.

11. The compound according to claim 1 , selected from the group consisting of:

or a pharmaceutically acceptable salt thereof.

12. A lipid composition comprising a compound according to claim 1 or a pharmaceutically acceptable salt thereof.

13. The lipid composition according claim 12 further comprising a biologically active agent.

14. The lipid composition according claim 13 wherein the biologically active agent is a siRNA.

15. The lipid composition according to claim 14 further comprising a helper lipid.

16. The lipid composition according to claim 15 further comprising a neutral lipid.

17. The lipid composition according to claim 16 further comprising a stealth lipid.

18. The lipid composition according to claim 17 wherein the helper lipid is cholesterol, the neutral lipid is DSPC, and the stealth lipid is PEG-DMG, S010 or S011.

19. The lipid composition according to claim 18 in the form of a lipid nanoparticle.

20. The lipid composition according to claim 19 having a molar ratio of about 44/about 45/about 9/about 2 of a compound of formula (I)/cholesterol/DSPC/S010 or S011, respectively.

21. A pharmaceutical composition comprising a lipid composition according to claim 14 and a pharmaceutically acceptable carrier or excipient.