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：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：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：US20230000994A1

公开(公告)日：2023-01-05

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 ,  Lawrence B. Snyder

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

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：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：US20210187108A1

公开(公告)日：2021-06-24

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： 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：US11173211B2

公开(公告)日：2021-11-16

申请号：US16563842

申请日：2019-09-07

申请人： ARVINAS OPERATIONS, INC. ,  YALE UNIVERSITY

发明人： Andrew P. Crew ,  Keith R. Hornberger ,  Jing Wang ,  Saul Jaime-Figueroa ,  Hanqing Dong

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

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：US11981683B2

公开(公告)日：2024-05-14

申请号：US17699082

申请日：2022-03-19

申请人： Arvinas Operations, Inc.

发明人： Erika Marina Vieira Araujo ,  Michael Berlin ,  Hanqing Dong ,  Steven M. Sparks ,  Jing Wang ,  Wei Zhang

IPC分类号： C07D401/14 ,  A61K45/06 ,  C07D413/14 ,  C07D417/14 ,  C07D471/04 ,  C07D471/10 ,  C07D487/08 ,  C07D487/10 ,  C07D498/10

CPC分类号： C07D498/10 ,  A61K45/06 ,  C07D401/14 ,  C07D413/14 ,  C07D417/14 ,  C07D471/04 ,  C07D471/10 ,  C07D487/08 ,  C07D487/10

摘要： Bifunctional compounds, which find utility as modulators of leucine-rich repeat kinase 2 (LRRK2), are described herein. In particular, the hetero-bifunctional compounds of the present disclosure contain on one end a moiety that binds to the cereblon E3 ubiquitin ligase and on the other end a moiety which binds LRRK2, 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：US20240131023A1

公开(公告)日：2024-04-25

申请号：US18460063

申请日：2023-09-01

申请人： Arvinas Operations, Inc.

发明人： LAWRENCE B. Snyder ,  Andrew P. Crew ,  Jing Wang ,  Hanqing Dong

IPC分类号： A61K31/496 ,  A61K31/167 ,  A61K31/277 ,  A61K31/337 ,  A61K31/417 ,  A61K31/4523 ,  A61K31/4545 ,  A61K31/497 ,  A61K31/501 ,  A61K31/506 ,  A61K31/5377 ,  A61K31/5386 ,  A61K31/57 ,  A61K31/661 ,  A61K31/663 ,  A61K31/675 ,  A61K38/09 ,  A61K47/54 ,  C07D401/12 ,  C07D401/14 ,  C07D413/12 ,  C07D413/14 ,  C07D498/10

CPC分类号： A61K31/496 ,  A61K31/167 ,  A61K31/277 ,  A61K31/337 ,  A61K31/417 ,  A61K31/4523 ,  A61K31/4545 ,  A61K31/497 ,  A61K31/501 ,  A61K31/506 ,  A61K31/5377 ,  A61K31/5386 ,  A61K31/57 ,  A61K31/661 ,  A61K31/663 ,  A61K31/675 ,  A61K38/09 ,  A61K47/545 ,  C07D401/12 ,  C07D401/14 ,  C07D413/12 ,  C07D413/14 ,  C07D498/10

摘要： This disclosure pertains to compounds, the preparation thereof, and the use of these compounds in the treatment of prostate cancer, including metastatic and/or castrate-resistant prostate cancer, in subjects in need thereof.