公开(公告)号：US20230203030A1

公开(公告)日：2023-06-29

申请号：US17931814

申请日：2022-09-13

申请人： Arvinas Operations, 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 ,  C07D417/14 ,  A61K45/06 ,  C07D417/12 ,  C07D403/06 ,  C07D403/14 ,  C07D401/14 ,  C07D413/14 ,  C07D405/14 ,  C07D495/04

CPC分类号： C07D471/04 ,  A61K45/06 ,  C07D401/14 ,  C07D403/06 ,  C07D403/14 ,  C07D405/14 ,  C07D413/14 ,  C07D417/12 ,  C07D417/14 ,  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：US20190315732A1

公开(公告)日：2019-10-17

申请号：US16375643

申请日：2019-04-04

申请人： Arvinas Operations, Inc. ,  Yale University

发明人： Andrew P. Crew ,  Keith R. Hornberger ,  Jing Wang ,  Hanging Dong ,  Michael Berlin ,  Craig M. Crews

IPC分类号： C07D417/14 ,  A61P35/00 ,  C07D401/14 ,  C07D413/14 ,  C07D471/04

摘要： The present disclosure relates to bifunctional compounds, which find utility as modulators of Kirsten rat sarcoma protein (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, accumulation, and/or overactivation of the target protein are treated or prevented with compounds and compositions of the present disclosure.

公开(公告)号：US20190192514A1

公开(公告)日：2019-06-27

申请号：US16284790

申请日：2019-02-25

申请人： Arvinas Operations, Inc.

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

IPC分类号： A61K31/506 ,  C07K5/062 ,  C07D417/04 ,  A61K45/06 ,  C07D413/04 ,  A61K47/66

CPC分类号： A61K31/506 ,  A61K45/06 ,  A61K47/665 ,  A61K2300/00 ,  C07D413/04 ,  C07D417/04 ,  C07K5/06034

摘要： The present invention relates to bifunctional compounds, which find utility to degrade and (inhibit) TBK1. In particular, the present invention is directed to compounds, which contain on one end an E3 ubiquitin ligase binding moiety which binds to an E3 ubiquitin ligase and on the other end a moiety which binds TBK1 such that TBK1 is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of TBK1. The present invention exhibits a broad range of pharmacological activities associated with compounds according to the present invention, consistent with the degradation/inhibition of TBK1.

公开(公告)号：US11986531B2

公开(公告)日：2024-05-21

申请号：US17387621

申请日：2021-07-28

申请人： ARVINAS OPERATIONS, INC. ,  YALE UNIVERSITY

发明人： Andrew P. Crew ,  Keith R. Hornberger ,  Jing Wang ,  Saul Jaime-Figueroa ,  Hanqing Dong ,  Kurt Zimmermann ,  Craig M. Crews

IPC分类号： C07D401/14 ,  A61K31/437 ,  A61K47/55 ,  A61P35/00 ,  C07D413/14 ,  C07D417/14 ,  C07D471/04 ,  C07D519/00

CPC分类号： A61K47/55 ,  C07D413/14 ,  C07D417/14 ,  C07D471/04 ,  C07D519/00

摘要： The present disclosure relates to bifunctional compounds, which find utility as modulators of Rapidly Accelerated Fibrosarcoma (RAF, such as c-RAF, A-RAF and/or B-RAF; the 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 RAF, 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, or the constitutive activation of the target protein, are treated or prevented with compounds and compositions of the present disclosure.

公开(公告)号：US11512083B2

公开(公告)日：2022-11-29

申请号：US16905641

申请日：2020-06-18

申请人： Arvinas Operations, 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

IPC分类号： C07D521/00 ,  C07D413/14 ,  C07D471/12 ,  C07D417/14 ,  C07D207/16 ,  C07D207/26 ,  C07D401/06 ,  C07D401/10 ,  C07D403/06 ,  C07D405/06 ,  C07D405/12 ,  C07D413/06 ,  C07D413/12 ,  A61K31/422 ,  A61K31/437 ,  A61K31/4439 ,  A61K31/5377 ,  C07D471/04 ,  A61K45/06 ,  C07D417/12 ,  C07D403/14 ,  C07D401/14 ,  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：US20220127279A1

公开(公告)日：2022-04-28

申请号：US17570197

申请日：2022-01-06

申请人： Arvinas Operations, Inc.

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

IPC分类号： C07D495/14 ,  A61K45/06 ,  C07D417/12 ,  C07D401/14 ,  C07D207/16 ,  C07D401/12 ,  C07D405/14 ,  A61K31/506 ,  A61K47/55 ,  A61K31/436 ,  A61K31/337 ,  A61K31/4995 ,  A61K31/593 ,  A61K31/4545 ,  A61K31/4184 ,  A61K31/704 ,  A61K31/664

摘要： The description relates to MDM2 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 MDM2 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：US11554171B2

公开(公告)日：2023-01-17

申请号：US16912329

申请日：2020-06-25

申请人： Arvinas Operations, Inc. ,  Yale University

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

IPC分类号： A61P35/00 ,  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：US20220370416A1

公开(公告)日：2022-11-24

申请号：US17223551

申请日：2021-04-06

申请人： Arvinas Operations, Inc. ,  Yale University

发明人： Ling Chu ,  Craig M. Crews ,  Hanqing Dong ,  Keith R. Hornberger ,  Jesus Raul Medina ,  Lawrence Snyder ,  Jing Wang

IPC分类号： A61K31/427 ,  A61K47/54 ,  A61K45/06 ,  A61K31/422 ,  A61K31/4155

摘要： Bifunctional compounds, which find utility as modulators of Kirsten ras sarcoma protein (KRas or KRAS), are described herein. In particular, the hetero-bifunctional compounds of the present disclosure contain on one end a moiety that binds to the Von Hippel-Lindau E3 ubiquitin ligase and on the other end a moiety which binds KRas, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The hetero-bifunctional compounds of the present disclosure exhibit a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aberrant regulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.

公开(公告)号：US20210139458A1

公开(公告)日：2021-05-13

申请号：US16889490

申请日：2020-06-01

申请人： Arvinas Operations, Inc.

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

IPC分类号： C07D401/14 ,  A61K31/4545 ,  A61K38/06 ,  C07D487/08 ,  C07D487/04 ,  A61P35/00 ,  A61K31/5386 ,  A61K38/05 ,  C07K5/083 ,  A61K31/497 ,  A61K47/54 ,  C07D498/10 ,  A61K45/06 ,  A61K31/454 ,  C07K5/078 ,  C07D487/10 ,  C07D401/04 ,  A61K31/501 ,  A61K31/519 ,  A61K31/4725 ,  C07D471/04 ,  C07D471/10 ,  A61K31/496 ,  A61P15/00 ,  A61K31/551

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：US10994015B2

公开(公告)日：2021-05-04

申请号：US15852854

申请日：2017-12-22

申请人： Arvinas Operations, Inc. ,  Yale University

发明人： Andrew P. Crew ,  Kurt Zimmermann ,  Jing Wang ,  Craig M. Crews ,  Saul Jaime-Figueroa ,  George Burslem

IPC分类号： C07D471/04 ,  A61P35/00 ,  A61K31/506 ,  A61K47/54 ,  A61K47/55 ,  A61K31/519 ,  A61K31/427 ,  A61K31/454 ,  A61K31/517 ,  A61K31/55 ,  A61K31/496 ,  A61K31/551 ,  A61K45/06 ,  A61K38/07 ,  A61K31/52

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.