公开(公告)号：US20180125821A1

公开(公告)日：2018-05-10

申请号：US15801243

申请日：2017-11-01

申请人： Arvinas, Inc.

发明人： Andrew P. Crew ,  Michael Berlin ,  John J. Flanagan ,  Hanqing Dong ,  Alexey Ishchenko

IPC分类号： A61K31/4166 ,  A61K31/495 ,  A61K31/381 ,  C07D401/14 ,  C07D417/14 ,  C07D401/04

摘要： 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.