Lipids and lipid compositions for the delivery of active agents

Patent metadata

Field	Value
Publication number	US-9504747-B2
Application number	US-201414200359-A
Country	US
Kind code	B2
Filing date	Mar 7, 2014
Priority date	Mar 8, 2013
Publication date	Nov 29, 2016
Grant date	Nov 29, 2016

Abstract

This invention provides for a compound of formula (I):

or a pharmaceutically acceptable salt thereof, wherein R 1 -R 4 , L and X 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):

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.

Assignees

• Baryza Jeremy Lee
• Beckwith Rohan Eric John
• Bowman Keith
• Byers Crystal
• Fazal Tanzina
• Gamber Gabriel Grant
• Lee Cameron Chuck-Munn
• Tichkule Ritesh Bhanudasji
• Vargeese Chandra
• Wang Shuangxi
• West Laura Ellen
• Zabawa Thomas
• Zhao Junping
• Novartis Ag

Inventors

• Baryza Jeremy Lee
• Beckwith Rohan Eric John
• Bowman Keith
• Byers Crystal
• Fazal Tanzina
• Gamber Gabriel Grant
• Lee Cameron Chuck-Munn
• Tichkule Ritesh Bhanudasji
• Vargeese Chandra
• Wang Shuangxi
• West Laura Ellen
• Zabawa Thomas
• Zhao Junping

Classifications

• C07C219/28

  having amino groups bound to acyclic carbon atoms of the carbon skeleton · CPC title

• C07C229/12

  to carbon atoms of acyclic carbon skeletons · CPC title

• C07C235/46

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

• C07C217/60

  linked by carbon chains having two carbon atoms between the amino groups and the six-membered aromatic ring or the condensed ring system containing that ring · CPC title

• C07D213/69

  Two or more oxygen atoms · CPC title