公开(公告)号：EP2802608A2

公开(公告)日：2014-11-19

申请号：EP13736209.1

申请日：2013-01-11

申请人： Yale University ,  GlaxoSmithKline Intellectual Property Development Limited ,  Cambridge Enterprise Limited University of Cambridge

发明人： CREWS, Craig, M. ,  BUCKLEY, Dennis ,  CIULLI, Alessio ,  JORGENSEN, William ,  GAREISS, Peter, C. ,  MOLLE, Inge, Van ,  GUSTAFSON, Jeffrey ,  TAE, Hyun-Seop ,  MICHEL, Julien ,  HOYER, Dentin, Wade ,  ROTH, Anke, G. ,  HARLING, John, David ,  SMITH, Ian Edward, David ,  MIAH, Afjal, Hussain ,  CAMPOS, Sebastien, Andre ,  LE, Joelle

IPC分类号： C07K19/00 ,  C07D413/12 ,  C07D413/14 ,  C07D207/26 ,  C07J9/00

CPC分类号： C07D413/14 ,  A61K31/422 ,  A61K31/427 ,  A61K31/437 ,  A61K31/4439 ,  A61K31/454 ,  A61K31/5377 ,  A61K38/05 ,  A61K38/06 ,  A61K45/06 ,  A61K47/545 ,  A61K47/64 ,  C07D207/16 ,  C07D207/26 ,  C07D401/06 ,  C07D401/10 ,  C07D403/06 ,  C07D405/06 ,  C07D405/12 ,  C07D413/06 ,  C07D413/12 ,  C07D417/12 ,  C07D417/14 ,  C07D471/04 ,  C07J43/003 ,  C12N9/93

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.