Compound usable as cationic lipid
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.
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.