Indazole based compounds and associated methods of use

Patent metadata

Field	Value
Publication number	US-12053469-B2
Application number	US-202117207325-A
Country	US
Kind code	B2
Filing date	Mar 19, 2021
Priority date	Mar 21, 2020
Publication date	Aug 6, 2024
Grant date	Aug 6, 2024

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 selected from:

or a pharmaceutically acceptable salt thereof.

2. A pharmaceutical composition comprising a compound of claim 1 , and a pharmaceutically acceptable carrier.

3. The pharmaceutical composition of claim 2 , wherein the composition further comprises an additional bioactive agent.

4. The pharmaceutical composition of claim 3 , wherein the additional bioactive agent is an anti-inflammatory agent, a chemotherapy agent, or an immunomodulatory agent.

5. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound of claim 1 for treating a disease or a disorder causally related to LRRK2 in a subject.

6. The pharmaceutical composition of claim 5 , wherein the disease or disorder is idiopathic Parkinson's disease (PD), LRRK2 mutation associated PD, primary tauopathies, Lewy body dementia, Crohn's Disease, Leprosy, or neuroinflammation.

Assignees

• Arvinas Operations Inc

Inventors

• Araujo Erika
• Berlin Michael M
• Sparks Steven M
• Wang Jing
• Zhang Wei

Classifications

• C07D487/10

  Spiro-condensed systems · CPC title

• C07D413/14

  containing three or more hetero rings · CPC title

• C07D401/14 Primary

  containing three or more hetero rings · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• A61K31/5377

  not condensed and containing further heterocyclic rings, e.g. timolol · CPC title