Compound usable as cationic lipid

Patent metadata

Field	Value
Publication number	US-11471533-B2
Application number	US-201716336668-A
Country	US
Kind code	B2
Filing date	Sep 27, 2017
Priority date	Sep 27, 2016
Publication date	Oct 18, 2022
Grant date	Oct 18, 2022

Abstract

The present invention provides a compound represented by formula (I) usable as a cationic lipid that facilitates introduction of a nucleic acid, for example, into a cell, and a composition or the like containing the compound.

First claim

The invention claimed is:

1. A compound represented by formula (I), or a pharmaceutically acceptable salt thereof:

wherein R 1 and R 2 are a hydrogen atom or C1-C3 alkyl;
A 1 and A 2 are linear or branched C8-C20 alkylene or C8-C20 alkenylene;
M 1 and M 2 are selected from the group consisting of —C═C—, —OC(O)—, —C(O)O—, —SC(O)—, —C(O)S—, —OC(S)—, —C(S)O—, —SS—, —C(R 5 )═N—, —N═C(R 5 )—, —C(R 5 )═N—O—, —O—N═C(R 5 )—, —N(R 5 )C(O)—, —C(O)N(R 5 )—, —N(R 5 )C(S)—, —C(S)N(R 5 )—, —N(R 5 )C(O)N(R 6 )—, —N(R 5 )C(O)O—, —OC(O)N(R 5 )—, and —OC(O)O—;
R 5 and R 6 are a hydrogen atom or C1-C3 alkyl; and
B 1 and B 2 are linear or branched C1-C16 alkyl or C2-C16 alkenyl.

2. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein R i and R 2 are a hydrogen atom or methyl.

3. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein A 1 and A 2 are linear or branched C8-C12 alkylene or C10-C14 alkenylene.

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

5. The compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein B 1 and B 2 are linear or branched C2-C9 alkyl or C3-C9 alkenyl.

6. 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 selected from the group consisting of (Z)-tetradec-9-enyl, (Z)-hexadec-9-enyl, (Z)-octadec-9-enyl, (E)-octadec-9-enyl, (Z)-octadec-11-enyl, (9Z,12Z)-octadeca-9,12-dienyl, (9Z,12Z,15Z)-octadeca-9,12,15-trienyl, (Z)-icos-11-enyl, (11Z,14Z)-icosa-11,14-dienyl, and (Z)-docos-13-enyl.

7. 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 selected from the group consisting of (Z)-hexadec-9-enyl, (Z)-octadec-9-enyl, (9Z,12Z)-octadeca-9,12-dienyl, and (11Z,14Z)-icosa-11,14-dienyl.

8. 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 selected from the following structures:

wherein n is an integer from 1 to 4.

9. 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.

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

11. The composition according to claim 10 , 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 related to tumor.

13. The composition according to claim 11 , wherein the target gene is a gene expressed in the liver, the lung, the kidney, or the spleen.

14. A medicament, comprising the composition according to claim 10 .

15. A method for introducing the nucleic acid into a cell using the composition according to claim 10 .

16. A treatment method for a disease related to the liver, the lung, the kidney or the spleen, comprising a step of administering the composition according to claim 10 to a human.

17. The treatment method according to claim 16 , wherein the composition is intravenously administered.

Assignees

• Kyowa Kirin Co Ltd

Inventors

• Hosoe Shintaro
• Yabuuchi Hayato

Classifications

• C12N15/113

  Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; {Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing (when used in plants C12N15/8218)} · CPC title

• C12N15/88

  using microencapsulation, e.g. using {amphiphile} liposome vesicle · CPC title

• A61K47/18 Primary

  Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids · CPC title

• C07C217/28

  having one amino group and at least two singly-bound oxygen atoms, with at least one being part of an etherified hydroxy group, bound to the carbon skeleton, e.g. ethers of polyhydroxy amines · CPC title

• C12N15/1137

  against enzymes (viral enzymes C12N15/1131; receptors C12N15/1138) · CPC title