公开(公告)号：US10730870B2

公开(公告)日：2020-08-04

申请号：US15074820

申请日：2016-03-18

申请人： Arvinas, Inc. ,  Yale University

发明人： Andrew P. Crew ,  Craig M. Crews ,  Xin Chen ,  Hanqing Dong ,  Caterina Ferraro ,  Yimin Qian ,  Kam Siu ,  Jing Wang ,  Meizhong Jin ,  Michael Berlin ,  Kurt Zimmermann ,  Lawrence Snyder

IPC分类号： C07D521/00 ,  C07D471/04 ,  C07D417/14 ,  A61K45/06 ,  C07D417/12 ,  C07D403/06 ,  C07D403/14 ,  C07D401/14 ,  C07D413/14 ,  C07D405/14 ,  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：US20160214972A1

公开(公告)日：2016-07-28

申请号：US15002303

申请日：2016-01-20

申请人： Arvinas, Inc.

发明人： Meizhong Jin ,  Andrew P. Crew ,  Hanqing Dong ,  Jing Wang ,  Kam Siu ,  Caterina Ferraro ,  Xin Chen ,  Yimin Qian

IPC分类号： C07D417/14 ,  C07D413/14 ,  A61K31/422 ,  A61K31/4439 ,  C07D417/12 ,  A61K45/06 ,  A61K31/4545 ,  C07D233/86 ,  C07D401/04 ,  C07D491/107 ,  C07D471/10 ,  A61K31/427 ,  C07D413/12

CPC分类号： C07D417/14 ,  A61K45/06 ,  A61P25/28 ,  A61P35/00 ,  C07D233/86 ,  C07D401/04 ,  C07D413/12 ,  C07D413/14 ,  C07D417/12 ,  C07D471/10 ,  C07D491/107 ,  C07K5/06165

摘要： The present invention relates to bifunctional compounds, which find utility to degrade and (inhibit) Androgen Receptor. 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 Androgen Receptor such that Androgen Receptor is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of Androgen Receptor. The present invention exhibits a broad range of pharmacological activities associated with compounds according to the present invention, consistent with the degradation/inhibition of Androgen Receptor.

摘要翻译： 本发明涉及双功能化合物，其可用于降解和（抑制）雄激素受体。 特别地，本发明涉及一种化合物，其一端含有与泛素连接酶结合的VHL配体，另一端含有结合雄激素受体的部分，使得雄激素受体置于接近泛素连接酶的作用下 降解（和抑制）雄激素受体。 与根据本发明的化合物相关的与雄激素受体的降解/抑制一致的本发明显示出广泛的药理学活性。

公开(公告)号：US20160058872A1

公开(公告)日：2016-03-03

申请号：US14792414

申请日：2015-07-06

申请人： Arvinas, Inc.

发明人： Andrew P. Crew ,  Craig Crews ,  Hanqing Dong ,  Jing Wang ,  Yimin Qian ,  Kam Siu ,  Meizhong Jin

IPC分类号： A61K47/48 ,  C07D495/14 ,  C07D417/14 ,  A61K31/426 ,  A61K31/505 ,  A61K31/454 ,  A61K31/551 ,  C07D401/14 ,  A61K45/06

CPC分类号： A61K31/426 ,  A61K31/454 ,  A61K31/505 ,  A61K31/551 ,  A61K45/06 ,  A61K47/545 ,  A61K47/555 ,  A61K47/66 ,  C07D401/04 ,  C07D401/14 ,  C07D409/14 ,  C07D417/14 ,  C07D487/04 ,  C07D495/14 ,  C07D498/14 ,  C07K14/4705 ,  C07K14/721 ,  C12N9/12 ,  C12N9/18 ,  C12Q1/25 ,  C12Y207/11001 ,  C12Y301/01031 ,  G01N2333/9015 ,  G01N2500/02

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.

公开(公告)号：US20160272639A1

公开(公告)日：2016-09-22

申请号：US15074820

申请日：2016-03-18

申请人： Arvinas, Inc. ,  Yale University

发明人： Andrew P. Crew ,  Craig M. Crews ,  Xin Chen ,  Hanqing Dong ,  Caterina Ferraro ,  Yimin Qian ,  Kam Siu ,  Jing Wang ,  Meizhong Jin ,  Michael Berlin ,  Kurt Zimmermann ,  Lawrence Snyder

IPC分类号： C07D471/04 ,  A61K31/427 ,  A61K45/06 ,  C07D417/12 ,  C07D403/06 ,  A61K31/4035 ,  C07D403/14 ,  A61K31/4155 ,  C07D401/14 ,  A61K31/454 ,  A61K31/4439 ,  A61K31/5377 ,  A61K31/437 ,  C07D413/14 ,  A61K31/4245 ,  C07D405/14 ,  A61K31/422 ,  A61K31/501 ,  A61K31/497 ,  A61K31/53 ,  C07D417/14

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.

摘要翻译： 本发明涉及双官能化合物，其可用作靶向泛素化的调节剂，特别是根据本发明的双官能化合物降解和/或以其它方式抑制的多种多肽和其它蛋白质的抑制剂。 特别地，本发明涉及化合物，其一端含有与泛素连接酶结合的VHL配体，另一端含有结合靶蛋白的部分，使得靶蛋白置于接近泛素连接酶 以实现该蛋白质的降解（和抑制）。 与靶向多肽的降解/抑制一致，本发明表现出与根据本发明的化合物相关的广泛的药理学活性。

公开(公告)号：US20150291562A1

公开(公告)日：2015-10-15

申请号：US14686640

申请日：2015-04-14

申请人： Arvinas, Inc.

发明人： Andrew P. Crew ,  Craig Crews ,  Hanqing Dong ,  Jing Wang ,  Yimin Qian ,  Kam Siu ,  Caterina Ferraro ,  Meizhong Jin ,  Xin Chen

IPC分类号： C07D401/14 ,  C07K14/72 ,  G01N33/573 ,  C12N9/18 ,  A61K47/48 ,  A61K45/06 ,  C12N9/12 ,  C07K14/47

CPC分类号： C07D401/14 ,  A61K31/4439 ,  A61K31/513 ,  A61K31/519 ,  A61K45/06 ,  A61K47/555 ,  A61K47/66 ,  C12N9/12 ,  C12N9/18 ,  C12Q1/25 ,  C12Y207/11001 ,  C12Y301/01031 ,  G01N2333/9015 ,  G01N2500/02 ,  A61K2300/00

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.

摘要翻译： 该描述涉及基于酰亚胺的化合物，包括其包含其的双官能化合物，其可用作靶向泛素化的调节剂，特别是根据本发明的双官能化合物降解和/或以其它方式抑制的多种多肽和其他蛋白质的抑制剂 发明。 特别地，该描述提供化合物，其在一端含有结合到脑片E3泛素连接酶的配体，另一端含有结合靶蛋白的部分，使得靶蛋白置于接近泛素连接酶的作用下 降解（和抑制）该蛋白质。 可以合成化合物，其表现出与几乎任何类型的靶向多肽的降解/抑制一致的广泛的药理活性。