Compound as cationic lipid

Patent metadata

Field	Value
Publication number	US-2019008975-A1
Application number	US-201616065222-A
Country	US
Kind code	A1
Filing date	Dec 26, 2016
Priority date	Dec 25, 2015
Publication date	Jan 10, 2019
Grant date	—

Abstract

The present invention provides a compound represented by formula (I) or a pharmaceutically acceptable salt thereof as a cationic lipid, and the like.

First claim

1 . A compound represented by formula (I):

wherein R 1 is a hydrogen atom, C1-C3 alkyl, hydroxyC2-C4 alkyl, di-C1-C3 alkylaminoC2-C4 alkyl, formula (A):

wherein R 2 and R 3 are, the same or different, a hydrogen atom or C1-C3 alkyl, or R 2 and R 3 , together with the nitrogen atom to which they are attached, may form a C2-C6 nitrogen-containing heterocycle, and n 3 is an integer from 2 to 6, or formula (B):

wherein R 4 and R 5 are, the same or different, a hydrogen atom or C1-C3 alkyl, or R 4 and R 5 , together with the nitrogen atom to which they are attached, may form a C2-C6 nitrogen-containing heterocycle, and n 4 is an integer from 1 to 6;
n 1 is an integer from 0 to 4; n 2 is an integer from 1 to 4, provided that the case where n 1 is 0 and n 2 is 1 is excluded;
Z 1 is, independently for each carbon atom bonded thereto, a hydrogen atom or C1-C3 alkyl;
Z 2 is, independently for each carbon atom bonded thereto, a hydrogen atom or C1-C3 alkyl;
A 1 and A 2 are, the same or different, linear or branched C8-C20 alkylene or C8-C20 alkenylene, or C6-C18 alkyleneoxyC1-C3 alkylene or C6-C18 alkenyleneoxyC1-C3 alkylene;
M 1 and M 2 are, the same or different, selected from the group consisting of —OC(O)—, —C(O)O—, —SC(O)—, —C(O)S—, —OC(S)—, —C(S)O—, —SS—, —C(R 6 )═N—, —N═C(R 6 )—, —C(R 6 )═N—O—, —O—N═C(R 6 )—, —N(R 6 )C(O)—, —C(O)N(R 6 )—, —N(R 6 )C(S)—, —C(S)N(R 6 )—, —N(R 6 )C(O)N(R 7 )—, —N(R 6 )C(O)O—, —OC(O)N(R 6 )—, and —OC(O)O—;
R 6 and R 7 are, the same or different, a hydrogen atom or C1-C4 alkyl; and
B 1 and B 2 are, the same or different, linear or branched C1-C16 alkyl or C2-C16 alkenyl or a pharmaceutically acceptable salt thereof.

2 . The compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein M 1 and M 2 are, the same or different, selected from the group consisting of —OC(O)—, —C(O)O—, —N(R 6 )C(O)—, and —C(O)N(R 6 )—.

3 . The compound according to claim 2 or a pharmaceutically acceptable salt thereof, wherein M 1 and M 2 are, the same or different, —OC(O)— or —C(O)O—.

4 . The compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein A 1 and A 2 are, the same or different, linear or branched C8-C20 alkylene or C8-C20 alkenylene.

5 . The compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein B 1 -M 1 -A 1 and B 2 -M 2 -A 2 - are the same.

6 . The compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein R 1 is C1-C3 alkyl.

7 . The compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein n 1 is 1, and n 2 is an integer from 1 to 3.

8 . The compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein both of n t and n 2 are 1.

9 . A composition comprising the compound according to claim 1 or a pharmaceutically acceptable salt thereof and a nucleic acid.

10 . The composition according to claim 9 , further comprising a neutral lipid and/or a polymer.

11 . The composition according to claim 9 , wherein the nucleic acid is a nucleic acid having a silencing effect on a target gene through the use of RNA interference (RNAi).

12 . The composition according to claim 11 , wherein the target gene is a gene expressed in the liver, the lung, the kidney, the digestive tract, the central nervous system, or the spleen.

13 . The composition according to claim 9 , wherein the composition is for intravenous administration.

14 . A medicament comprising the composition according to claim 9 .

15 . (canceled)

16 . A method for treating a disease related to the liver, the lung, the kidney, the digestive tract, the central nervous system, or the spleen, comprising administering the composition according to claim 9 to a patient in need thereof.

17 . (canceled)

Assignees

• Kyowa Hakko Kirin Co Ltd

Inventors

• Hosoe Shintaro
• Naoi Tomoyuki

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61K31/40

  having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil · CPC title

• A61K31/397

  having four-membered rings, e.g. azetidine · CPC title

• C07D205/04

  having no double bonds between ring members or between ring members and non-ring members · CPC title