公开(公告)号：EP3337476A1

公开(公告)日：2018-06-27

申请号：EP16837498.1

申请日：2016-08-05

申请人： Arvinas, Inc. ,  Yale University

发明人： QIAN, Yimin ,  DONG, Hanqing ,  WANG, Jing ,  BERLIN, Michael ,  SIU, Kam ,  CREW, Andrew, P. ,  CREWS, Craig, M.

IPC分类号： A61K31/4025 ,  A61K31/5517 ,  C07K5/08 ,  C07D519/00

CPC分类号： A61K45/06 ,  A61K47/55 ,  C07D417/14 ,  C07D495/14 ,  C07D519/00

摘要： The present invention relates to bifunctional compounds, which find utility as modulators of targeted ubiquitination, especially inhibitors of a variety of polypeptides and other proteins which are degraded and/or otherwise inhibited by bifunctional compounds according to the present invention. In particular, the present invention is directed to compounds, which contain on one end a VHL ligand which binds to the ubiquitin ligase and on the other end a moiety which binds a target protein such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of that protein. The present invention exhibits a broad range of pharmacological activities associated with compounds according to the present invention, consistent with the degradation/inhibition of targeted polypeptides.

公开(公告)号：EP3270917A1

公开(公告)日：2018-01-24

申请号：EP16765865.7

申请日：2016-03-18

申请人： Arvinas, Inc. ,  Yale University

发明人： BERLIN, Michael ,  ZIMMERMAN, Kurt ,  SNYDER, Lawrence ,  CREW, Andrew P. ,  CREWS, Craig M. ,  CHEN, Xin ,  DONG, Hanqing ,  FERRARO, Caterina ,  JIN, Meizhong ,  QIAN, Yimin ,  SIU, Kam ,  WANG, Jing

IPC分类号： A61K31/4025 ,  C07D207/16 ,  C07D417/12

CPC分类号： C07D471/04 ,  A61K45/06 ,  C07D401/14 ,  C07D403/06 ,  C07D403/14 ,  C07D405/14 ,  C07D413/14 ,  C07D417/12 ,  C07D417/14 ,  C07D495/04

摘要： The present invention relates to bifunctional compounds, which find utility as modulators of targeted ubiquitination, especially inhibitors of a variety of polypeptides and other proteins which are degraded and/or otherwise inhibited by bifunctional compounds according to the present invention. In particular, the present invention is directed to compounds, which contain on one end a VHL ligand which binds to the ubiquitin ligase and on the other end a moiety which binds a target protein such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of that protein. The present invention exhibits a broad range of pharmacological activities associated with compounds according to the present invention, consistent with the degradation/inhibition of targeted polypeptides.

公开(公告)号：EP3302572A1

公开(公告)日：2018-04-11

申请号：EP16804586.2

申请日：2016-06-03

申请人： Arvinas, Inc.

发明人： CREWS, Craig, M. ,  CREW, Andrew, P. ,  DONG, Hanqing ,  WANG, Jing ,  QIAN, Yimin ,  SIU, Kam ,  JIN, Meizhong

IPC分类号： A61K47/48 ,  C07D401/14

CPC分类号： C07D401/14 ,  A61K47/545 ,  A61P35/00 ,  C07D401/04 ,  C07D495/14

摘要： The description relates to imide- based compounds, including bifunctional. compounds comprising the same, which find utility as modulators of targeted ubiquitination, especially inhibitors of a variety of polypeptides and other proteins which are degraded and/or otherwise inhibited by bifunctional compounds according to the present invention. In particular, the description provides compounds, which contain on one end a ligand which binds to the cereblon E3 ubiquitin ligase and on the other end a moiety which binds a target protein such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of that protein. Compounds can be synthesized that exhibit a broad range of pharmacological activities consistent with the degradation/inhibition of targeted polypeptides of nearly any type.