公开(公告)号：US20220064168A1

公开(公告)日：2022-03-03

申请号：US17207330

申请日：2021-03-19

Applicant: Arvinas Operations, Inc.

Inventor： Erika Araujo ,  Michael Berlin ,  Steven M. Sparks ,  Jing Wang ,  Wei Zhang

IPC: C07D487/04 ,  C07D519/00 ,  A61K45/06

Abstract: Bifunctional compounds, which find utility as modulators of non-receptor Leucine-rich repeat kinase 2 (LRRK2), are described herein. In particular, the 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 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.

公开(公告)号：US20210315896A1

公开(公告)日：2021-10-14

申请号：US17207325

申请日：2021-03-19

Applicant: Arvinas Operations, Inc.

Inventor： Erika Araujo ,  Michael M. Berlin ,  Steven M. Sparks ,  Jing Wang ,  Wei Zhang

IPC: A61K31/506 ,  A61K45/06 ,  C07D401/14 ,  C07D487/10 ,  A61K31/496 ,  C07D413/14 ,  A61K31/5377 ,  A61P25/16

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.