Ionizable cationic lipid for RNA delivery

Patent metadata

Field	Value
Publication number	US-9850202-B2
Application number	US-201715423008-A
Country	US
Kind code	B2
Filing date	Feb 2, 2017
Priority date	Nov 18, 2013
Publication date	Dec 26, 2017
Grant date	Dec 26, 2017

Abstract

What is described is a compound

wherein
R 1 and R 2 are the same or different, each a linear or branched alkyl with 1-9 carbons, or an alkenyl or alkynyl with 2 to 11 carbons; L 1 and L 2 are the same or different, each a linear alkyl having 3 to 18 carbons; X 1 and X 3 are —CO—O—; X 3 is S or O; L 3 is a lower alkyl; R 3 is a lower alkyl; and R 4 and R 5 are the same or different, each a lower alkyl;

or a pharmaceutically acceptable salt thereof.

First claim

What is claimed:

1. A compound of formula I

wherein
R 1 is a branched alkyl of 3, 4, 5, 6, 7, 8, or 9 carbons,
R 2 is a linear or branched alkyl of 1, 2, 3, 4, 5, 6, 7, 8, or 9 carbons, an alkenyl or alkynyl of 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11 carbons, or cholesteryl,
L 1 and L 2 are the same or different, each a linear alkylene or alkenylene of 3 or 4 carbons,
X 1 is —CO—O— whereby -L 2 -CO—O—R 2 is formed,
X 2 is S or O,
X 3 is —CO—O— whereby -L 1 -CO—O—R 1 is formed,
L 3 is a bond, or a linear or branched alkylene of 1, 2, 3, 4, 5 or 6 carbons,
R 3 is a linear or branched alkylene of 1, 2, 3, 4, 5 or 6 carbons, and
R 4 and R 5 are the same or different, each hydrogen or a linear or branched alkyl of 1, 2, 3, 4, 5 or 6 carbons;

or a pharmaceutically acceptable salt thereof.

2. The compound of claim 1 , wherein L 1 and L 2 are the same.

3. The compound of claim 2 , wherein L 1 and L 2 are propylene.

4. The compound of claim 1 , wherein R 1 and R 2 are the same.

5. The compound of claim 1 , wherein L 3 is a bond.

6. A compound of formula 2

wherein
R 1 is branched alkyl of 3, 4, 5, 6, 7, 8, or 9 carbons,
R 2 is a linear or branched alkyl of 1, 2, 3, 4, 5, 6, 7, 8, or 9 carbons, an alkenyl or alkynyl of 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11 carbons, or cholesteryl,
L 1 and L 2 are the same or different, each a linear alkylene or alkenylene of 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, or 18 carbons,
X 1 is —CO—O— whereby -L 2 -CO—O—R 2 is formed,
X 2 is S or O,
X 3 is-CO—O— whereby -L 1 -CO—O—R 1 is formed,
L 3 is a bond, or a linear or branched alkylene of 1, 2, 3, 4, 5 or 6 carbons,
R 3 is a linear or branched alkylene of 1, 2, 3, 4, 5 or 6 carbons, and
R 4 and R 5 are the same or different, each a hydrogen, or a linear or branched alkyl of 1, 2, 3, 4, 5 or 6 carbons;

or a pharmaceutically acceptable salt thereof.

7. The compound of claim 6 , wherein L 3 is methylene.

8. The compound of claim 6 , wherein R 4 and R 5 are independently methyl or ethyl.

9. The compound of claim 6 , wherein R 3 is ethylene or propylene.

10. The compound of claim 6 , wherein X 2 is S.

11. The compound of claim 6 , wherein R 1 and R 2 are the same.

12. The compound of claim 11 , wherein R 2 is an alkyl of 1, 2, or 3 carbons.

13. The compound of claim 11 , wherein R 2 is an alkenyl of 9, 10, or 11 carbons.

14. The compound of claim 6 , wherein L 1 and L 2 are the same.

15. The compound of claim 14 , wherein L 1 and L 2 are an alkylene of 3, 4, 5, 6, or 7 carbons.

16. The compound of claim 14 , wherein L 1 and L 2 are an alkenylene of 13, 14, or 15 carbons.

17. The compound of claim 6 , wherein X 2 is 0.

18. The compound of claim 6 , wherein L 3 is a bond.

19. A compound of formula I

wherein
R 1 and R 2 are the same or different, each a linear or branched alkyl of 1, 2, 3, 4, 5, 6, 7, 8, or 9 carbons, an alkenyl or alkynyl of 2, 3, 4, 5, 6, 7, 8, 9, 10 or 11 carbons, or cholesteryl,
L 1 and L 2 are propylene,
X 1 is —CO—O— whereby -L 2 -CO—O—R 2 is formed,
X 2 is S or O,
X 3 is −CO—O— whereby -L 1 -CO—O—R 1 is formed,
L 3 is a linear or branched alkylene of 1, 2, 3, 4, 5 or 6 carbons,
R 3 is a linear or branched alkylene of 1, 2, 3, 4, 5 or 6 carbons, and
R 4 and R 5 are the same or different, each hydrogen or a linear or branched alkyl of 1, 2, 3, 4, 5 or 6 carbons;

or a pharmaceutically acceptable salt thereof.

20. A compound of formula 2

wherein
R 1 and R 2 are the same, each an alkyl of 1, 2, or 3 carbons,
L 1 and L 2 are the same or different, each a linear alkylene or alkenylene of 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, or 18 carbons,
X 1 is —CO—O— whereby -L 2 -CO—O—R 2 is formed,
X 2 is S or O,
X 3 is —CO—O— whereby -L 1 -CO—O—R 1 is formed,
L 3 is a linear or branched alkylene of 1, 2, 3, 4, 5 or 6 carbons,
R 3 is a linear or branched alkylene of 1, 2, 3, 4, 5 or 6 carbons, and
R 4 and R 5 are the same or different, each a hydrogen, or a linear or branched alkyl of 1, 2, 3, 4, 5 or 6 carbons;

or a pharmaceutically acceptable salt thereof.

Assignees

• Arcturus Therapeutics Inc

Inventors

• Payne Joseph E
• Chivukula Padmanabh

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• C12N2320/32

  Special delivery means, e.g. tissue-specific · CPC title

• C07C323/52 Primary

  the carbon skeleton being acyclic and saturated · CPC title

• C07C271/22 Primary

  to carbon atoms of hydrocarbon radicals substituted by carboxyl groups · CPC title

• C07C333/04

  having nitrogen atoms of thiocarbamic groups bound to hydrogen atoms or to acyclic carbon atoms · CPC title