公开(公告)号：US11912699B2

公开(公告)日：2024-02-27

申请号：US16932590

申请日：2020-07-17

Applicant: Arvinas Operations, Inc.

Inventor： Andrew P. Crew ,  Michael Berlin ,  Angela M. Cacace ,  Julian T. Chandler

IPC: C07D417/14 ,  A61K47/54 ,  C07D401/04 ,  C07D487/04 ,  A61K45/06

CPC classification number: C07D417/14 ,  A61K47/54 ,  C07D401/04 ,  C07D487/04 ,  A61K45/06

Abstract: The present disclosure relates to bifunctional compounds, which find utility as modulators of tau protein. In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a VHL or cereblon ligand which binds to the E3 ubiquitin ligase and on the other end a moiety which binds tau protein, such that tau protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of tau. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of tau protein. Diseases or disorders that result from aggregation or accumulation of tau protein are treated or prevented with compounds and compositions of the present disclosure.

公开(公告)号：US20220315575A1

公开(公告)日：2022-10-06

申请号：US16932590

申请日：2020-07-17

Applicant: Arvinas Operations, Inc.

Inventor： Andrew P. Crew ,  Michael Berlin ,  Hanqing Dong ,  Alexey Ishchenko ,  Angela M. Cacace ,  Julian T. Chandler

IPC: C07D417/14 ,  A61K47/54 ,  C07D401/04 ,  C07D487/04

Abstract: The present disclosure relates to bifunctional compounds, which find utility as modulators of tau protein. In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a VHL or cereblon ligand which binds to the E3 ubiquitin ligase and on the other end a moiety which binds tau protein, such that tau protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of tau. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of tau protein. Diseases or disorders that result from aggregation or accumulation of tau protein are treated or prevented with compounds and compositions of the present disclosure.