Lipids and lipid compositions for the delivery of active agents

Patent metadata

Field	Value
Publication number	US-10426737-B2
Application number	US-201415104723-A
Country	US
Kind code	B2
Filing date	Dec 17, 2014
Priority date	Dec 19, 2013
Publication date	Oct 1, 2019
Grant date	Oct 1, 2019

Abstract

This invention provides for a compound of formula (I) or a pharmaceutically acceptable salt thereof, wherein R 1 -R 3 , n, p, L 1 and L 2 are defined herein. The compounds of formula (I) and pharmaceutically acceptable salts thereof are cationic lipids useful in the delivery of biologically active agents to cells and tissues.

First claim

What is claimed is:

1. A compound of formula (I) or a pharmaceutically acceptable salt thereof:

wherein:
n is 0, 1, 2, 3 or 4;
p is 0, 1, 2, 3, 4, 5, 6, 7 or 8;
L 1 is —O— or a bond;
L 2 is —OC(O)— or —C(O)O—;
R 1 is

v is 0, 1, 2, 3 or 4;
w is 0, 1, 2 or 3;
R and R′ are each, independently, hydrogen or C 1-8 alkyl;
R 2 is selected from: (i) C 6-20 alkyl optionally substituted with a hydroxyl, and (ii) C 15-19 alkenyl;
R 3 is selected from: C 4-22 alkyl, C 12-22 alkenyl,

2. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein the compound is of formula (II):

3. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein the compound is of formula (III):

4. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein R 2 is selected from:

5. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein the compound is of formula (IV):

6. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein R 3 is selected from:

7. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein the compound is of formula (V):

8. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein the compound is of formula (VI):

9. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein the compound is of formula (VII):

10. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein R 1 is selected from:

11. The compound of claim 1 or a pharmaceutically acceptable salt, wherein R 1 is

12. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein the compound is selected from:
2-(10-dodecyl-3-ethyl-8,14-dioxo-7,9,13-trioxa-3-azaoctadecan-18-yl)propane-1,3-diyl dioctanoate;
2-(9-dodecyl-2-methyl-7,13-dioxo-6,8,12-trioxa-2-azaheptadecan-17-yl)propane-1,3-diyl dioctanoate;
2-(9-dodecyl-2-methyl-7,13-dioxo-6,8,12-trioxa-2-azapentadecan-15-yl)propane-1,3-diyl dioctanoate;
2-(10-dodecyl-3-ethyl-8,14-dioxo-7,9,13-trioxa-3-azahexadecan-16-yl)propane-1,3-diyl dioctanoate;
2-(8-dodecyl-2-methyl-6,12-dioxo-5,7,11-trioxa-2-azaheptadecan-17-yl)propane-1,3-diyl dioctanoate;
2-(10-dodecyl-3-ethyl-8,14-dioxo-7,9,13-trioxa-3-azanonadecan-19-yl)propane-1,3-diyl dioctanoate;
2-(9-dodecyl-2-methyl-7,13-dioxo-6,8,12-trioxa-2-azaoctadecan-18-yl)propane-1,3-diyl dioctanoate;
2-(8-dodecyl-2-methyl-6,12-dioxo-5,7,11-trioxa-2-azaoctadecan-18-yl)propane-1,3-diyl dioctanoate;
2-(10-dodecyl-3-ethyl-8,14-dioxo-7,9,13-trioxa-3-azaicosan-20-yl)propane-1,3-diyl dioctanoate;
2-(9-dodecyl-2-methyl-7,13-dioxo-6,8,12-trioxa-2-azanonadecan-19-yl)propane-1,3-diyl dioctanoate;
3-(((3-(diethylamino)propoxy)carbonyl)oxy)pentadecyl 4,4-bis(octyloxy)butanoate;
3-(((3-(diethylamino)propoxy)carbonyl)oxy)pentadecyl 4,4-bis((2-ethyl hexyl)oxy)butanoate;
3-(((3-(diethylamino)propoxy)carbonyl)oxy)pentadecyl 4,4-bis((2-propylpentyl)oxy)butanoate;
3-(((3-(ethyl(methyl)amino)propoxy)carbonyl)oxy)pentadecyl 4,4-bis((2-propylpentyl)oxy)butanoate;
3-(((3-(dimethylamino)propoxy)carbonyl)oxy)pentadecyl 4,4-bis((2-propylpentyl)oxy)butanoate;
3-(((3-(diethylamino)propoxy)carbonyl)oxy)pentadecyl 6,6-bis(octyloxy)hexanoate;
3-(((3-(diethylamino)propoxy)carbonyl)oxy)pentadecyl 6,6-bis(hexyloxy)hexanoate;
3-(((3-(diethylamino)propoxy)carbonyl)oxy)pentadecyl 6,6-bis((2-ethyl hexyl)oxy)hexanoate;
3-(((3-(diethylamino)propoxy)carbonyl)oxy)pentadecyl 8,8-bis(hexyloxy)octanoate;
3-(((3-(diethylamino)propoxy)carbonyl)oxy)pentadecyl 8,8-dibutoxyoctanoate;
3-(((3-(diethylamino)propoxy)carbonyl)oxy)pentadecyl 8,8-bis((2-propylpentyl)oxy)octanoate;
3-(((3-(ethyl(methyl)amino)propoxy)carbonyl)oxy)pentadecyl 8,8-bis((2-propylpentyl)oxy)octanoate;
3-(((3-(dimethylamino)propoxy)carbonyl)oxy)pentadecyl 8,8-bis((2-propylpentyl)oxy)octanoate;
3-(((3-(dimethylamino)propoxy)carbonyl)oxy)pentadecyl 3-octylundecanoate;
3-(((3-(dimethylamino)propoxy)carbonyl)oxy)pentadecyl 3-octylundec-2-enoate;
3-(((3-(dimethylamino)propoxy)carbonyl)oxy)pentadecyl 7-hexyltridec-6-enoate;
3-(((3-(dimethylamino)propoxy)carbonyl)oxy)pentadecyl 9-pentyltetradecanoate;
3-(((3-(dimethylamino)propoxy)carbonyl)oxy)pentadecyl 9-pentyltetradec-8-enoate;
3-(((3-(dimethylamino)propoxy)carbonyl)oxy)pentadecyl 5-heptyldodecanoate;
3-(((3-(dimethylamino)propoxy)carbonyl)oxy)tridecyl 5-heptyldodecanoate;
3-(((3-(dimethylamino)propoxy)carbonyl)oxy)undecyl 5-heptyldodecanoate;
1,3-bis(octanoyloxy)propan-2-yl (3-(((2-(dimethylamino)ethoxy)carbonyl)oxy)pentadecyl) succinate;
1,3-bis(octanoyloxy)propan-2-yl (3-(((3-(dimethylamino)propoxy)carbonyl)oxy)pentadecyl) succinate;
1-(3-(((3-(dimethylamino)propoxy)carbonyl)oxy)pentadecyl) 10-octyl decanedioate;
1-(3-(((3-(diethylamino)propoxy)carbonyl)oxy)pentadecyl) 10-octyl decanedioate;
1-(3-(((3-(ethyl(methyl)amino)propoxy)carbonyl)oxy)pentadecyl) 10-octyl decanedioate;
1-(3-(((3-(diethylamino)propoxy)carbonyl)oxy)pentadecyl) 10-(2-ethylhexyl) decanedioate;
1-(3-(((3-(ethyl(methyl)amino)propoxy)carbonyl)oxy)pentadecyl) 10-(2-ethylhexyl) decanedioate;
3-(((3-(dimethylamino)propoxy)carbonyl)oxy)pentadecyl 10-(octanoyloxy)decanoate;
8-dodecyl-2-methyl-6,12-dioxo-5,7,11-trioxa-2-azanonadecan-19-yl decanoate;
3-(((3-(diethylamino)propoxy)carbonyl)oxy)pentadecyl 10-(octanoyloxy)decanoate;
3-(((3-(ethyl(methyl)amino)propoxy)carbonyl)oxy)pentadecyl 10-(octanoyloxy)decanoate;
(9Z,12Z)-3-(((3-(dimethylamino)propoxy)carbonyl)oxy)pentadecyl octadeca-9,12-dienoate;
(9Z,12Z)-3-(((3-(diethylamin

Assignees

• Novartis Ag

Inventors

• Brito Luis
• Chen Delai
• Gamber Gabriel Grant
• Geall Andrew
• Love Kevin
• Zabawa Thomas
• Zecri Frederic

Classifications

• C07C219/06

  having the hydroxy groups esterified by carboxylic acids having the esterifying carboxyl groups bound to hydrogen atoms or to acyclic carbon atoms of an acyclic saturated carbon skeleton · CPC title

• C07D207/16

  Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals · CPC title

• C12N2760/00034

  Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein · CPC title

• C07C323/52

  the carbon skeleton being acyclic and saturated · CPC title

• A61K9/5123 Primary

  Organic compounds, e.g. fats, sugars · CPC title