- 专利标题: Compounds and methods for the targeted degradation of rapidly accelerated fibrosarcoma polypeptides
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申请号: US15853166申请日: 2017-12-22
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公开(公告)号: US10723717B2公开(公告)日: 2020-07-28
- 发明人: Andrew P. Crew , Keith R. Hornberger , Jing Wang , Hanqing Dong , Yimin Qian , Craig M. Crews , Saul Jaime-Figueroa
- 申请人: Arvinas, Inc. , Yale University
- 申请人地址: US CT New Haven US CT New Haven
- 专利权人: ARVINAS OPERATIONS, INC.,YALE UNIVERSITY
- 当前专利权人: ARVINAS OPERATIONS, INC.,YALE UNIVERSITY
- 当前专利权人地址: US CT New Haven US CT New Haven
- 代理机构: Cantor Colburn LLP
- 代理商 Bryan D. Zerhusen, Esq.; Nicholas R. Herrel, Esq.
- 主分类号: C07D519/00
- IPC分类号: C07D519/00 ; C07D401/14 ; C07D401/04 ; A61K31/4439 ; C07D417/14 ; A61K31/4545 ; C07D487/04 ; A61P9/00 ; C07D471/04 ; A61K31/437 ; A61K45/06 ; A61P35/00 ; A61P43/00 ; A61P25/00 ; A61K31/4188 ; A61K47/54 ; A61K47/55
摘要:
The present disclosure relates to bifunctional compounds, which find utility as modulators of Rapidly Accelerated Fibrosarcoma (RAF, such as c-RAF, A-RAF and/or B-RAF; the target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a Von Hippel-Lindau, cereblon, Inhibitors of Apotosis Proteins or mouse double-minute homolog 2 ligand which binds to the respective E3 ubiquitin ligase and on the other end a moiety which binds the target protein RAF, 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, or the constitutive activation of the target protein, are treated or prevented with compounds and compositions of the present disclosure.
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