Compound or salt thereof and lipid particles

Patent metadata

Field	Value
Publication number	US-12285525-B2
Application number	US-202017112239-A
Country	US
Kind code	B2
Filing date	Dec 4, 2020
Priority date	Jun 8, 2018
Publication date	Apr 29, 2025
Grant date	Apr 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. A compound represented by Formula (1) or a salt thereof,

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,
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 compound or a salt thereof according to claim 1 ,
wherein X represents —NR 1 —, and R 1 has the same definition as R 1 in claim 1 .

3. The compound or a salt thereof 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.

4. The compound or a salt thereof according to claim 1 ,
wherein the compound represented by Formula (1) is a compound represented by Formula (1-1),

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,
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.

5. The compound or a salt thereof according to claim 1 ,
wherein X represents —O—.

6. The compound or a salt thereof 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.

7. The compound or a salt thereof according to claim 1 ,
wherein R 4 , R 6 , R 9 , R 10 , R 11 , and R 12 each represent a hydrogen atom.

8. The compound or a salt thereof 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 —.

9. The compound or a salt thereof 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 substituted and the substituent on the substituted or unsubstituted aryl group and on the substituted or unsubstituted heteroaryl group have the same definitions as those in claim 1 ,
a+b is 1, and c+d is 1 or 2.

10. The compound or a salt thereof according to claim 1 ,
wherein the compound represented by Formula (1) is a compound represented by Formula (2),

in the formula, 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,

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