Ionizable cationic lipid for RNA delivery
What is described is a compound of formula I consisting of a compound in which R 1 is a branched chain alkyl consisting of 10 to 31 carbons; R 2 is a linear alkyl, alkenyl, or alkynyl consisting of 2 to 20 carbons; L 1 and L 2 are the same or different, each a linear alkylene of 1 to 20 carbons or a linear alkenylene of 2 to 20 carbons; X 1 is S or O; R 3 is a linear or branched alkylene consisting of 1 to 6 carbons; and R 4 and R 5 are the same or different, each a hydrogen or a linear or branched alkyl consisting of 1 to 6 carbons; or a pharmaceutically acceptable salt thereof.
1. A compound of formula I
wherein
R 1 is CH((CH 2 ) n CH 3 ) 2 or CH((CH 2 ) n CH 3 )((CH 2 ) n-1 CH 3 ) wherein n is 4, 5, 6, 7, or 8,
R 2 is a linear alkyl, alkenyl or alkynyl consisting of 2 to 20 carbons,
R 3 is a linear or branched alkylene consisting of 1 to 6 carbons,
R 4 and R 5 are the same or different, each a hydrogen or a linear or branched alkyl consisting of 1 to 6 carbons;
L 1 is a linear alkylene of 1 to 3 carbons,
L 2 is a linear alkylene of 1 to 5 carbons, and
X 1 is S;
or a salt or solvate thereof.
2. The compound of claim 1 , wherein R 3 consists of ethylene or propylene.
3. The compound of claim 1 , wherein R 4 and R 5 separately are methyl or ethyl.
4. The compound of claim 1 , wherein L 2 is an alkylene consisting of 1, 2, or 3 carbons.
5. The compound of claim 1 , wherein R 2 is an alkenyl.
6. The compound of claim 5 wherein R 2 is an alkenyl consisting of 9 carbons.
7. The compound of claim 1 , wherein n is 5 and L 1 is an alkylene consisting of 1 or 3 carbons.
8. The compound of claim 1 , wherein n is 6 and L 1 is an alkylene consisting of 3 carbons.
9. The compound of claim 1 , wherein n is 7.
10. The compound of claim 1 , wherein n is 8 and L 1 is an alkylene consisting of 1 or 3 carbons.
11. The compound of claim 5 , wherein R 1 consists of —CH((CH 2 ) n CH 3 )((CH 2 ) n-1 CH 3 ), wherein n is 7 or 8.
12. A compound selected from the group consisting of compounds of formulas ATX-43, ATX-57, ATX-58, ATX-61, ATX-63, ATX-64, ATX-81, ATX-82, ATX-83, ATX-86, ATX-87, and ATX-88
or a salt or solvate thereof.
13. The compound of claim 12 of formula ATX-57
14. The compound of claim 12 of formula ATX-58
15. The compound of claim 12 of formula ATX-81
16. The compound of claim 12 of formula ATX-88