Ionizable cationic lipid for RNA delivery
What is described is a compound of formula III or IV wherein R 1 is a branched alkyl with 12 to 20 carbons; R 2 is a linear alkyl with 5 to 10 carbons or a branched alkyl with 12 to 20 carbons; L 1 and L 2 are each a bond or a linear alkylene having 1 to 3 carbon atoms, when L 3 is a bond; L 1 and L 2 are each a linear alkylene or alkenylene 5 to 18 carbon atoms, when L 3 is an alkylene of 5 to 18 carbons; X is S or O; R 3 is of a lower alkyl; and R 4 and R 5 are the same or different, each a lower alkyl; or a pharmaceutically acceptable salt thereof.
1. A compound of formula I
wherein
R is a linear alkenyl of 2-18 carbons or an alkynal of 2-18 carbons;
L is a linear alkylene or alkenylene of 6 to 18 carbon atoms;
X is —CO—O— or —O—CO—;
Y is S or O;
R 1 is a linear or branched alkylene of 1 to 6 carbons; and
R 2 and R 3 are the same or different, each a hydrogen or a linear or branched alkyl consisting of 1 to 6 carbons; and
n is 1-6;
or a salt or solvate thereof.
2. The compound of claim 1 , wherein Y is S.
3. The compound of claim 1 , wherein R 1 is ethylene, n-propylene, or isopropylene.
4. The compound of claim 1 , wherein R 2 and R 3 each is methyl, ethyl, or isopropyl.
5. The compound of claim 1 , wherein n is 1.
6. The compound of claim 1 , wherein R is an alkenyl.
7. The compound of claim 1 , wherein R is an alkynyl.
8. A compound of formula I
wherein
R is a branched alkyl or alkenyl consisting of one branch, wherein the branched alkyl or alkenyl has 3-18 carbons;
L is a linear alkylene or alkenylene of 6 to 18 carbon atoms;
X—R is —CO—O—R;
Y is S or O;
R 1 is a linear or branched alkylene of 1 to 6 carbons; and
R 2 and R 3 are the same or different, each a hydrogen or a linear or branched alkyl consisting of 1 to 6 carbons; and
n is 1-6;
or a salt or solvate thereof.
9. The compound of claim 8 , wherein Y is S.
10. The compound of claim 8 , wherein R 1 is ethylene, n-propylene, or isopropylene.
11. The compound of claim 8 , wherein R 2 and R 3 each is methyl, ethyl, or isopropyl.
12. The compound of claim 8 , wherein n is 1.
13. The compound of claim 8 , wherein R has 3-12 carbons.
14. The compound of claim 8 , wherein R consists of one or two double bonds.
15. The compound of claim 1 , wherein R consists of one or two double bonds.