Trialkyne Linking Agents and Methods of Use

Patent metadata

Field	Value
Publication number	US-2025092072-A1
Application number	US-202418773657-A
Country	US
Kind code	A1
Filing date	Jul 16, 2024
Priority date	Feb 17, 2018
Publication date	Mar 20, 2025
Grant date	—

Abstract

Described are improved linking agents that are useful for facilitating the attachment of targeting groups, pharmacokinetic (PK) enhancers or modifiers, or other delivery agents to oligonucleotides. The described linking agents may exhibit improved reaction yields, stability, and biological activity, particularly when used in connection with oligonucleotide-based compounds, such as RNA interference (RNAi) agents.

First claim

1 - 17 . (canceled)

18 . A compound of Formula II,

or a pharmaceutically acceptable salt thereof,
wherein,
L 1 , L 2 , and L 3 are each independently linkers comprising optionally substituted alkylene;
L 4 is a linker comprising optionally substituted alkylene, optionally substituted arylene, and optionally substituted cycloalkylene;
each instance of R 1 is optionally substituted alkyl;
R 2 is optionally substituted alkyl; and
R 4 is H or optionally substituted alkyl.

19 - 24 . (canceled)

25 . A compound of Formula III,

or a pharmaceutically acceptable salt thereof,
wherein,
L 1 , L 2 , and L 3 are each independently linkers comprising optionally substituted alkylene;
L 4 is a linker comprising optionally substituted alkylene, optionally substituted arylene, and optionally substituted cycloalkylene;
R 4 is H or optionally substituted alkyl;
X is O or S; and
RNA comprises or consists of an RNAi agent.

26 - 31 . (canceled)

32 . The compound or pharmaceutically acceptable salt thereof of claim 25 , wherein the compound is selected from the group consisting of:

Compound

No.
Structure

1-O-III

1-S-III

2-O-III

2-S-III

3-O-III

3-S-III

4-O-III

4-S-III

5-O-III

5-S-III

6-O-III

6-S-III

7-O-III

7-S-III

8-O-III

8-S-III

9-O-III

9-S-III

10-O-III

10-S-III

11-O-III

Assignees

• Arrowhead Pharmaceuticals Inc

Inventors

• Li Zhen
• Altenhofer Erich
• Carlson Jeffrey
• Fowler-Watters Matthew
• Chen Bo

Classifications

• C07C2602/44

  the bicyclo ring system containing eight carbon atoms · CPC title

• C07C2602/38

  the bicyclo ring system containing five carbon atoms · CPC title

• C07C2601/14

  The ring being saturated · CPC title

• C07B2200/07

  Optical isomers · CPC title

• A61K47/65

  Peptidic linkers, binders or spacers, e.g. peptidic enzyme-labile linkers · CPC title