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：US11352351B2

公开(公告)日：2022-06-07

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 ,  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 ,  C07K5/078 ,  A61P35/00 ,  A61P25/28

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.

公开(公告)号：US20180346461A1

公开(公告)日：2018-12-06

申请号：US16048191

申请日：2018-07-27

申请人： Arvinas, Inc.

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

IPC分类号： C07D417/14 ,  A61P25/28 ,  A61P35/00 ,  C07K5/078 ,  C07D413/14 ,  C07D417/12 ,  C07D471/10 ,  C07D491/107 ,  C07D401/04 ,  C07D233/86 ,  C07D413/12 ,  A61K45/06

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.

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。

公开(公告)号：US10647698B2

公开(公告)日：2020-05-12

申请号：US15829541

申请日：2017-12-01

申请人： Arvinas, Inc.

发明人： Andrew P. Crew ,  Yimin Qian ,  Hanqing Dong ,  Jing Wang

IPC分类号： 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 ,  C07K5/062

摘要： 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.

公开(公告)号：US10604506B2

公开(公告)日：2020-03-31

申请号：US15881318

申请日：2018-01-26

申请人： Arvinas, Inc.

发明人： Andrew P. Crew ,  Keith R. Hornberger ,  Hanqing Dong ,  Jing Wang ,  Yimin Qian ,  Craig M. Crews

IPC分类号： C07D401/14 ,  C07D471/04 ,  C07D409/12 ,  C07D403/06 ,  A61P35/00 ,  C07D405/14 ,  C07D413/14 ,  C07D417/12 ,  C07D417/14 ,  C07D403/14

摘要： 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 a cereblon, Von Hippel-Lindau ligase-binding moiety, 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, 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.

公开(公告)号：US20180177750A1

公开(公告)日：2018-06-28

申请号：US15851053

申请日：2017-12-21

申请人： Arvinas, Inc.

发明人： Andrew P. Crew ,  Lawrence B. Snyder ,  Jing Wang ,  Hanqing Dong ,  Yimin Qian ,  Michael Berlin

IPC分类号： A61K31/166 ,  A61K31/405 ,  A61K47/54 ,  A61K31/351 ,  A61K38/45 ,  C12N9/10 ,  A61P35/00

CPC分类号： A61K31/166 ,  A61K31/351 ,  A61K31/405 ,  A61K38/45 ,  A61K47/545 ,  A61K47/55 ,  A61K47/555 ,  A61P35/00 ,  C07D401/14 ,  C07D405/12 ,  C07D405/14 ,  C07D409/14 ,  C07D417/14 ,  C07D471/04 ,  C12N9/1007 ,  C12Y201/01043

摘要： The present disclosure relates to bifunctional compounds, which find utility as modulators of enhancer of zeste homolog 2 (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, 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.

公开(公告)号：US20180125821A1

公开(公告)日：2018-05-10

申请号：US15801243

申请日：2017-11-01

申请人： Arvinas, Inc.

发明人： Andrew P. Crew ,  Michael Berlin ,  John J. Flanagan ,  Hanqing Dong ,  Alexey Ishchenko

IPC分类号： A61K31/4166 ,  A61K31/495 ,  A61K31/381 ,  C07D401/14 ,  C07D417/14 ,  C07D401/04

摘要： The present disclosure relates to bifunctional compounds, which find utility as modulators of tau protein. In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a VHL or cereblon ligand which binds to the E3 ubiquitin ligase and on the other end a moiety which binds tau protein, such that tau protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of tau. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of tau protein. Diseases or disorders that result from aggregation or accumulation of tau protein are treated or prevented with compounds and compositions of the present disclosure.

公开(公告)号：US20170037004A1

公开(公告)日：2017-02-09

申请号：US15209648

申请日：2016-07-13

申请人： Arvinas, Inc.

发明人： Andrew P. Crew ,  Michael Berlin ,  Hanqing Dong ,  Yimin Qian

IPC分类号： C07D207/16 ,  C07D417/14 ,  A61K31/496 ,  C07D471/04 ,  A61K31/444 ,  A61K45/06 ,  A61K31/506 ,  C07D487/14 ,  A61K31/551 ,  C07D519/00 ,  C07D403/12 ,  A61K31/4178 ,  A61K31/40 ,  A61K31/4439

CPC分类号： C07D207/16 ,  A61K31/40 ,  A61K31/4178 ,  A61K31/4439 ,  A61K31/444 ,  A61K31/496 ,  A61K31/506 ,  A61K31/551 ,  A61K38/00 ,  A61K45/06 ,  A61K47/55 ,  C07D401/04 ,  C07D403/04 ,  C07D403/12 ,  C07D405/14 ,  C07D417/04 ,  C07D417/14 ,  C07D471/04 ,  C07D487/14 ,  C07D495/14 ,  C07D519/00 ,  C07K2319/00

摘要： The description relates to Inhibitors of Apoptosis Proteins (IAPs) binding 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 IAP 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： 该描述涉及凋亡蛋白（IAP）结合化合物的抑制剂，包括其中包含其的双官能化合物，其可用作靶向泛素化的调节剂，特别是多种多肽和其他蛋白质的抑制剂，其被降解和/或以其它方式被双功能抑制 根据本发明的化合物。 特别地，该描述提供化合物，其一端含有与IAP E3泛素连接酶结合的配体，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。