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.

公开(公告)号：US20240091204A1

公开(公告)日：2024-03-21

申请号：US18309867

申请日：2023-09-18

申请人： Arvinas Operations, Inc.

发明人： Andrew P. Crew ,  Hanqing Dong ,  Michael Berlin ,  Steven M. Sparks

IPC分类号： A61K31/427 ,  A61K31/4035 ,  A61K31/4245 ,  A61K31/437 ,  A61K31/4439 ,  A61K31/496 ,  A61K31/541 ,  A61K47/54

CPC分类号： A61K31/427 ,  A61K31/4035 ,  A61K31/4245 ,  A61K31/437 ,  A61K31/4439 ,  A61K31/496 ,  A61K31/541 ,  A61K47/555

摘要： The present disclosure relates to bifunctional compounds, which find utility as modulators of α-synuclein (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：US11707452B2

公开(公告)日：2023-07-25

申请号：US16545983

申请日：2019-08-20

申请人： Arvinas Operations, Inc.

发明人： Andrew P. Crew ,  Hanqing Dong ,  Michael Berlin ,  Steven M. Sparks

IPC分类号： A61K31/427 ,  A61K47/54 ,  A61K31/4035 ,  A61K31/4245 ,  A61K31/437 ,  A61K31/4439 ,  A61K31/496 ,  A61K31/541

CPC分类号： A61K31/427 ,  A61K31/4035 ,  A61K31/4245 ,  A61K31/437 ,  A61K31/4439 ,  A61K31/496 ,  A61K31/541 ,  A61K47/555

摘要： The present disclosure relates to bifunctional compounds, which find utility as modulators of α-synuclein (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：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：US20220267305A1

公开(公告)日：2022-08-25

申请号：US17727386

申请日：2022-04-22

申请人： Arvinas Operations, Inc.

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

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：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：US12036209B2

公开(公告)日：2024-07-16

申请号：US17196695

申请日：2021-03-09

申请人： Arvinas Operations, Inc.

发明人： Andrew P. Crew ,  Erika Araujo

IPC分类号： A61K31/437 ,  A61K31/422 ,  A61K31/427 ,  A61K31/551 ,  A61K38/20 ,  A61K38/53 ,  A61K47/64 ,  A61P21/04 ,  A61P25/00 ,  A61P29/00 ,  A61P35/00 ,  A61P37/06 ,  C07D401/14 ,  C07D417/14 ,  C07D487/04

CPC分类号： A61K31/437 ,  A61K31/422 ,  A61K31/427 ,  A61K31/551 ,  A61K38/2006 ,  A61K38/53 ,  A61K47/642 ,  A61P21/04 ,  A61P25/00 ,  A61P29/00 ,  A61P35/00 ,  A61P37/06 ,  C07D401/14 ,  C07D417/14 ,  C07D487/04

摘要： The present disclosure relates to bifunctional compounds, which find utility as modulators of Interleukin-1 Receptor-Associated Kinase 4 (IRAK-4); the target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a Von Hippel-Lindau, cereblon, ligand which binds to the 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：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：US11912699B2

公开(公告)日：2024-02-27

申请号：US16932590

申请日：2020-07-17

申请人： Arvinas Operations, Inc.

发明人： Andrew P. Crew ,  Michael Berlin ,  Angela M. Cacace ,  Julian T. Chandler

IPC分类号： C07D417/14 ,  A61K47/54 ,  C07D401/04 ,  C07D487/04 ,  A61K45/06

CPC分类号： C07D417/14 ,  A61K47/54 ,  C07D401/04 ,  C07D487/04 ,  A61K45/06

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.