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：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：US10584101B2

公开(公告)日：2020-03-10

申请号：US15730728

申请日：2017-10-11

申请人： Arvinas, Inc.

发明人： Andrew P. Crew ,  Lawrence B. Snyder ,  Jing Wang

IPC分类号： C07D401/14 ,  C07D233/42 ,  A61K31/166 ,  C07D211/76 ,  C07D241/04 ,  C07D231/12 ,  C07D213/72 ,  C07D205/04 ,  C07D237/08 ,  C07D239/24 ,  C07D221/20 ,  A61K31/277 ,  A61K47/10 ,  A61K31/02 ,  A61K31/497 ,  C07D209/48 ,  A61K45/06

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：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.