Compound or salt thereof and lipid particles

Patent metadata

Field	Value
Publication number	US-12370143-B2
Application number	US-202418443959-A
Country	US
Kind code	B2
Filing date	Feb 16, 2024
Priority date	Jun 8, 2018
Publication date	Jul 29, 2025
Grant date	Jul 29, 2025

Abstract

An object of the present invention is to provide a compound or a salt thereof constituting lipid particles that can achieve a high nucleic acid encapsulation rate and excellent delivery of nucleic acids, and to provide lipid particles that can achieve a high nucleic acid encapsulation rate and excellent delivery of nucleic acids. According to an aspect of the present invention, a compound represented by Formula (1) or a salt thereof is provided.

In the formula, X represents —NR 1 — or —O—, R 1 represents a hydrogen atom, a hydrocarbon group, or the like, R 2 and R 3 each independently represent a hydrogen atom, a hydrocarbon group, or the like, R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , and R 12 each independently represent a hydrogen atom or an alkyl group,
groups in any one or more pairs among R 4 and R 5 , R 10 and R 5 , R 5 and R 12 , R 4 and R 6 , R 5 and R 6 , R 6 and R 7 , R 6 and R 10 , R 12 and R 7 , and R 7 and R 8 may be linked to each other to form a 4- to 7-membered ring which may contain an O atom, a, b, c, and d are each independently represent an integer of 0 to 3, a+b is equal to or greater than 1, and c+d is equal to or greater than 1.

First claim

What is claimed is:

1. Lipid particles comprising:
a compound represented by Formula (1) or a salt thereof; and
a nucleic acid,

wherein in the formula, X represents —NR 1 — or —O—,
R 1 represents a hydrogen atom, a hydrocarbon group having 6 to 24 carbon atoms, or a group represented by R 21 -L 1 -R 22 —, R 21 represents a hydrocarbon group having 1 to 24 carbon atoms, L 1 represents —O(CO)O—, —O(CO)—, —(CO)O—, —O—, or a group represented by the following formula,

R 22 represents a divalent hydrocarbon linking group having 1 to 18 carbon atoms,
R 2 and R 3 each independently represent a hydrogen atom, a hydrocarbon group having 3 to 24 carbon atoms, or a group represented by R 31 -L 2 -R 32 —, R 31 represents a hydrocarbon group having 1 to 24 carbon atoms, L 2 represents —O(CO)O—, —O(CO)—, —(CO)O—, —O—, or a group represented by the following formula,

R 32 represents a divalent hydrocarbon linking group having 1 to 18 carbon atoms,
R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , and R 12 each independently represent a hydrogen atom or an alkyl group having 1 to 18 carbon atoms that may be substituted,
groups in any one or more pairs among R 4 and R 5 , R 10 and R 5 , R 5 and R 12 , R 4 and R 6 , R 5 and R 6 , R 6 and R 7 , R 6 and R 10 , R 12 and R 7 , and R 7 and R 8 may be linked to each other to form a 4- to 7-membered ring which may contain an O atom,
a substituent on the alkyl group having 1 to 18 carbon atoms that may be substituted is a hydroxyl group, a carboxyl group, an amino group represented by —NR 45 R 46 , a substituted or unsubstituted aryl group, a substituted or unsubstituted heteroaryl group, or a group represented by —O(CO)O—R 41 , —O(CO)—R 42 , —(CO)O—R 43 , or —O—R 44 , R 41 , R 42 , R 43 , R 44 , R 45 , and R 46 each independently represent a hydrocarbon group having 1 to 18 carbon atoms,
a substituent on the substituted or unsubstituted aryl group and on the substituted or unsubstituted heteroaryl group is an alkyl group having 1 to 18 carbon atoms, a hydroxyl group, a carboxyl group, an amino group represented by —NR 45 R 46 , or a group represented by —O(CO)O—R 41 , —O(CO)—R 42 , —(CO)O—R 43 , or —O—R 44 , R 41 , R 42 , R 43 , R 44 , R 45 , and R 46 each independently represent a hydrocarbon group having 1 to 18 carbon atoms,
a, b, c, and d each independently represent an integer of 0 to 3, a+b is equal to or greater than 1, and c+d is equal to or greater than 1.

2. The lipid particles according to claim 1 , further comprising a lipid.

3. The lipid particles according to claim 2 , wherein the lipid is at least one kind of lipid selected from the group consisting of a neutral lipid and a lipid having a nonionic hydrophilic polymer.

4. The lipid particles according to claim 1 , further comprising a sterol.

5. The lipid particles according to claim 1 ,
wherein X represents —NR 1 —, and R 1 has the same definition as R 1 in claim 1 .

6. The lipid particles according to claim 1 ,
wherein X represents —NR 1 —, R 1 represents a hydrocarbon group having 6 to 24 carbon atoms, or a group represented by R 21 -L 1 -R 22 —, R 21 , L 1 , and R 22 have the same definitions as R 21 , L 1 , and R 22 in claim 1 respectively;
one of R 2 and R 3 represents a hydrogen atom and the other represents a hydrocarbon group having 3 to 24 carbon atoms or a group represented by R 31 -L 2 -R 32 —, and R 31 , L 2 , and R 32 have the same definitions as R 31 , L 2 , and R 32 in claim 1 respectively.

7. The lipid particles according to claim 1 ,
wherein the compound represented by Formula (1) is a compound represented by Formula (1-1),

wherein R 24 represents a hydrogen atom, a hydrocarbon group having 6 to 24 carbon atoms, or a group represented by R 21 -L 1 -R 22 —, R 21 represents a hydrocarbon group having 1 to 24 carbon atoms, L 1 represents —O(CO)O—, —O(CO)—, —(CO)O—, —O—, or a group represented by the following formula,

R 22 represents a divalent hydrocarbon linking group having 1 to 18 carbon atoms,
R 25 represents a hydrogen atom, a hydrocarbon group having 3 to 24 carbon atoms, or a group represented by R 31 -L 2 -R 32 —, R 31 represents a hydrocarbon group having 1 to 24 carbon atoms, L 2 represents —O(CO)O—, —O(CO)—, —(CO)O—, —O—, or a group represented by the following formula,

R 32 represents a divalent hydrocarbon linking group having 1 to 18 carbon atoms,
R 4 , R 5 , R 6 , R 7 , R 8 , R 10 , and R 12 each independently represent a hydrogen atom or an alkyl group having 1 to 18 carbon atoms that may be substituted,
groups in any one or more pairs among R 4 and R 5 , R 10 and R 5 , R 5 and R 12 , R 4 and R 6 , R 5 and R 6 , R 6 and R 7 , R 6 and R 10 , R 12 and R 7 , and R 7 and R 8 may be linked to each other to form a 4- to 7-membered ring which may contain an O atom,
a substituent on the alkyl group having 1 to 18 carbon atoms that may be substituted is a hydroxyl group, a carboxyl group, an amino group represented by —NR 45 R 46 , a substituted or unsubstituted aryl group, a substituted or unsubstituted heteroaryl group, or a group represented by —O(CO)O—R 41 , —O(CO)—R 42 , —(CO)O—R 43 , or —O—R 44 , R 41 , R 42 , R 43 , R 44 , R 45 , and R 46 each independently represent a hydrocarbon group having 1 to 18 carbon atoms,
a substituent on the substituted or unsubstituted aryl group and on the substituted or unsubstituted heteroaryl group is an alkyl group having 1 to 18 carbon atoms, a hydroxyl group, a carboxyl group, an amino group represented by —NR 45 R 46 , or a group represented by —O(CO)O—R 41 , —O(CO)—R 42 , —(CO)O—R 43 , or —O—R 44 , and R 41 , R 42 , R 43 , R 44 , R 45 , and R 46 each independently represent a hydrocarbon group having 1 to 18 carbon atoms.

8. The lipid particles according to claim 1 ,
wherein X represents —O—.

9. The lipid particles according to claim 1 ,
wherein X represents —O—,
R 2 and R 3 each independently represent a hydrocarbon group having 3 to 24 carbon atoms or a group represented by R 31 -L 2 -R 32 —, and R 31 , L 2 , and R 32 have the same definitions as R 31 , L 2 , and R 32 in claim 1 respectively.

10. The lipid particles according to claim 1 ,
wherein R 4 , R 6 , R 9 , R 10 , R 11 , and R 12 each represent a hydrogen atom.

11. The lipid particles according to claim 1 ,
wherein R 2 and R 3 each independently represent a hydrogen atom, a hydrocarbon group having 6 to 24 carbon atoms, or a group represented by R 31 -L 2 -R 32 —.

12. The lipid particles according to claim 1 ,
wherein X represents —O—,
R 2 , R 3 , R 31 , L 2 , and R 32 have the same definitions as R 2 , R 3 , R 31 , L 2 , and R 32 in claim 1 respectively,
R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , and R 12 each independently represent a hydrogen atom or an alkyl group having 1 to 18 carbon atoms that may be substituted,
a substituent on the alkyl group having 1 to 18 carbon atoms that may be su

Assignees

• Fujifilm Corp

Inventors

• Tanabe Shintaro
• Yamamoto Masahiko
• Sato Kimihiko
• TAKAHASHI Motomasa
• Tsuna Kazuhiro
• Tasaki Yasutaka
• Endo Taisuke
• Doi Issei
• Fukunaga Hirofumi

Classifications

• C12N15/88

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

• 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

• A61K9/1278

  Post-loading, e.g. by ion or pH gradient · CPC title

• A61K31/7088 Primary

  Compounds having three or more nucleosides or nucleotides · CPC title

• A61K48/0033

  the non-active part being non-polymeric · CPC title