Indazole based compounds and associated methods of use

Patent metadata

Field	Value
Publication number	US-12559506-B2
Application number	US-202418659374-A
Country	US
Kind code	B2
Filing date	May 9, 2024
Priority date	Mar 19, 2021
Publication date	Feb 24, 2026
Grant date	Feb 24, 2026

Abstract

Bifunctional compounds, which find utility as modulators of leucine-rich repeat kinase 2 (LRRK2), are described herein. In particular, the hetero-bifunctional compounds of the present disclosure contain on one end a moiety that binds to the cereblon E3 ubiquitin ligase and on the other end a moiety which binds LRRK2, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The hetero-bifunctional compounds of the present disclosure exhibit a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aberrant regulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.

First claim

What is claimed is:

1 . A compound, wherein the compound is:

or a pharmaceutically acceptable salt thereof.

2 . A compound, wherein the compound is:

or a pharmaceutically acceptable salt thereof.

3 . A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

4 . A pharmaceutical composition comprising the compound of claim 2 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

5 . The pharmaceutical composition of claim 3 , wherein the composition further comprises an additional bioactive agent.

6 . The pharmaceutical composition of claim 4 , wherein the composition further comprises an additional bioactive agent.

7 . The pharmaceutical composition of claim 5 , wherein the additional bioactive agent is an anti-inflammatory agent, a chemotherapy agent, or an immunomodulatory agent.

8 . The pharmaceutical composition of claim 6 , wherein the additional bioactive agent is an anti-inflammatory agent, a chemotherapy agent, or an immunomodulatory agent.

9 . A method of treating a disease, a disorder, or a symptom causally related to LRRK2 in a subject, comprising administering to the subject a compound, or pharmaceutically acceptable salt thereof, of claim 1 , or a pharmaceutical composition comprising a compound of claim 2 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

10 . A method of treating a disease, a disorder, or a symptom causally related to LRRK2 in a subject, comprising administering to the subject a compound, or pharmaceutically acceptable salt thereof, of claim 2 , or a pharmaceutical composition comprising a compound of claim 2 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

11 . The method of claim 9 , wherein the disease or disorder is Park

Assignees

• Arvinas Operations Inc

Inventors

• Araujo Erika Marina Vieira
• Berlin Michael
• Dong Hanqing
• Sparks Steven M
• Wang Jing
• Zhang Wei

Classifications

• C07D487/10

  Spiro-condensed systems · CPC title

• C07D487/08

  Bridged systems · CPC title

• C07D471/10

  Spiro-condensed systems · CPC title

• C07D471/04

  Ortho-condensed systems · CPC title

• C07D417/14

  containing three or more hetero rings · CPC title