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公开(公告)号:US20220388984A1
公开(公告)日:2022-12-08
申请号:US17359424
申请日:2021-06-25
Applicant: Arvinas Operations, Inc.
Inventor: Andrew P. Crew , Hanqing Dong , Keith R. Hornberger , Yimin Quian , Jing Wang
IPC: C07D401/14 , A61K47/54 , A61P15/00 , A61P35/00 , A61K31/454 , A61K31/4545 , A61K31/4725 , A61K31/496 , A61K31/497 , A61K31/501 , A61K31/519 , A61K31/5386 , A61K31/551 , A61K38/05 , A61K38/06 , A61K45/06 , C07D401/04 , C07D471/04 , C07D471/10 , C07D487/04 , C07D487/08 , C07D487/10 , C07D498/10 , C07K5/078 , C07K5/083
Abstract: The present disclosure relates to bifunctional compounds, which find utility as modulators of estrogen receptor (target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end at least one of a Von Hippel-Lindau ligand, a cereblon ligand, Inhibitors of Apoptosis Proteins ligand, mouse double-minute homolog 2 ligand, or a combination thereof, which binds to the respective E3 ubiquitin ligase, and on the other end a moiety which binds the target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aggregation or accumulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.