公开(公告)号：US20180099940A1

公开(公告)日：2018-04-12

申请号：US15730728

申请日：2017-10-11

申请人： Arvinas, Inc.

发明人： Andrew P. Crew ,  Keith R. Hornberger ,  Lawrence B. Snyder ,  Kurt Zimmermann ,  Jing Wang ,  Michael Berlin ,  Craig M. Crews ,  Hanqing Dong

IPC分类号： C07D233/42 ,  C07D209/48 ,  C07D211/76 ,  C07D241/04 ,  C07D231/12 ,  C07D213/72 ,  C07D205/04 ,  C07D237/08 ,  C07D239/24 ,  C07D221/20 ,  A61K31/277 ,  A61K47/10 ,  A61K31/02 ,  A61K31/497 ,  A61K31/166

摘要： The present disclosure relates to bifunctional compounds, which find utility to degrade and (inhibit) Androgen Receptor. In particular, the present disclosure is directed to compounds, which contain on one end a cereblon ligand which binds to the E3 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 disclosure exhibits a broad range of pharmacological activities associated with compounds according to the present disclosure, consistent with the degradation/inhibition of Androgen Receptor.

公开(公告)号：US20180193470A1

公开(公告)日：2018-07-12

申请号：US15852854

申请日：2017-12-22

申请人： Arvinas, Inc. ,  Yale University

发明人： Andrew P. Crew ,  Kurt Zimmermann ,  Jing Wang ,  Michael Berlin ,  Hanqing Dong ,  Alexey Ishchenko ,  Yimin Qian ,  Craig M. Crews ,  Saul Jaime-Figueroa ,  George Burslem

IPC分类号： A61K47/54 ,  A61K47/55 ,  A61K31/519 ,  A61K31/427 ,  A61K31/454 ,  A61K31/517 ,  A61K31/506 ,  A61K31/496 ,  A61K31/551 ,  A61K45/06 ,  A61K38/07 ,  A61K31/52 ,  A61K31/55

摘要： The present disclosure relates to bifunctional compounds, which find utility as modulators of receptor tyrosine kinase (RTK) proteins. In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a ligand which binds to an 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 effectuate ubiquitination, and therefore, degradation (and inhibition) of the 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：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：US20170065719A1

公开(公告)日：2017-03-09

申请号：US15230354

申请日：2016-08-05

申请人： Arvinas, Inc. ,  Yale University

发明人： Yimin Qian ,  Hanqing Dong ,  Jing Wang ,  Michael Berlin ,  Andrew P. Crew ,  Craig M. Crews

IPC分类号： A61K47/48 ,  A61K45/06 ,  A61K31/422 ,  A61K31/437 ,  A61K31/551 ,  A61K31/427

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：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：US11458123B2

公开(公告)日：2022-10-04

申请号：US15801243

申请日：2017-11-01

申请人： Arvinas, Inc.

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

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

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：US10772962B2

公开(公告)日：2020-09-15

申请号：US15230354

申请日：2016-08-05

申请人： Arvinas, Inc. ,  Yale University

发明人： Yimin Qian ,  Hanqing Dong ,  Jing Wang ,  Michael Berlin ,  Andrew P. Crew ,  Craig M. Crews

IPC分类号： C07D521/00 ,  A61K45/06 ,  C07D519/00 ,  C07D417/14 ,  C07D495/14 ,  A61K47/55

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：US20180228907A1

公开(公告)日：2018-08-16

申请号：US15953108

申请日：2018-04-13

申请人： Arvinas, Inc.

发明人： Andrew P. Crew ,  Craig M. Crews ,  Hanqing Dong ,  Keith R. Hornberger ,  Jing Wang ,  Yimin Qian ,  Kurt Zimmermann ,  Michael Berlin ,  Lawrence B. Snyder

IPC分类号： A61K47/55 ,  C07D401/04 ,  C07D401/14 ,  C07D471/04 ,  A61K31/437 ,  A61K31/496 ,  A61K31/551 ,  A61K45/06 ,  A61K31/501 ,  A61K31/506 ,  A61K31/497

CPC分类号： A61K47/55 ,  A61K31/437 ,  A61K31/496 ,  A61K31/497 ,  A61K31/501 ,  A61K31/506 ,  A61K31/551 ,  A61K45/06 ,  A61K47/545 ,  A61P35/00 ,  C07D401/04 ,  C07D401/14 ,  C07D471/04

摘要： The description relates to cereblon E3 ligase 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 disclosure. 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：US20180215731A1

公开(公告)日：2018-08-02

申请号：US15885671

申请日：2018-01-31

申请人： Arvinas, Inc.

发明人： Andrew P. Crew ,  Michael Berlin ,  Hanqing Dong ,  Keith R. Homberger ,  Yimin Qian ,  Lawrence B. Snyder ,  Jing Wang ,  Kurt Zimmermann

IPC分类号： C07D401/14 ,  C07D417/14 ,  C07D471/04 ,  C07D471/10 ,  C07D487/04 ,  C07D495/14 ,  C07D498/04 ,  A61P35/02

CPC分类号： C07D401/14 ,  A61P35/02 ,  C07D417/14 ,  C07D471/04 ,  C07D471/10 ,  C07D487/04 ,  C07D495/14 ,  C07D498/04

摘要： The description relates to cereblon E3 ligase 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 disclosure. 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：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.