公开(公告)号：US11912699B2

公开(公告)日：2024-02-27

申请号：US16932590

申请日：2020-07-17

Applicant: Arvinas Operations, Inc.

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

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

CPC classification number: C07D417/14 ,  A61K47/54 ,  C07D401/04 ,  C07D487/04 ,  A61K45/06

Abstract: 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：US11512083B2

公开(公告)日：2022-11-29

申请号：US16905641

申请日：2020-06-18

Applicant: Arvinas Operations, Inc. ,  Yale University

Inventor： 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: 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

Abstract: 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：US11191741B2

公开(公告)日：2021-12-07

申请号：US15851053

申请日：2017-12-21

Applicant: ARVINAS OPERATIONS, INC.

Inventor： Andrew P. Crew ,  Lawrence B. Snyder ,  Jing Wang ,  Yimin Qian ,  Michael Berlin

IPC: A61K31/166 ,  A61K31/405 ,  A61K47/54 ,  A61P35/00 ,  A61K38/45 ,  C12N9/10 ,  A61K31/351 ,  C07D471/04 ,  C07D401/14 ,  C07D405/14 ,  C07D405/12 ,  C07D417/14 ,  C07D409/14 ,  A61K47/55

Abstract: 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.

公开(公告)号：US20200085793A1

公开(公告)日：2020-03-19

申请号：US16545983

申请日：2019-08-20

Applicant: Arvinas Operations, Inc.

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

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

Abstract: 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：US20250064945A1

公开(公告)日：2025-02-27

申请号：US18709947

申请日：2022-11-23

Applicant: Arvinas Operations, Inc. ,  Genentech, Inc.

Inventor： Michael Berlin ,  Huifen Chen ,  Peter Scott Dragovich ,  Leanna Renee Staben ,  Jing Wang

IPC: A61K47/55 ,  A61K31/519 ,  A61K47/54 ,  C07D487/04 ,  C07D519/00

Abstract: The present disclosure relates to bifunctional compounds, which find utility as modulators of SMARCA2 or BRM (target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a ligand that binds to the Von Hippel-Lindau 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：US20250059198A1

公开(公告)日：2025-02-20

申请号：US18710130

申请日：2022-11-23

Applicant: Arvinas Operations, Inc. ,  Genentech, Inc.

Inventor： Michael Berlin ,  Fabio Broccatelli ,  Huifen Chen ,  Peter Scott Dragovich ,  Jing Wang

IPC: C07D487/08 ,  A61K31/501 ,  A61K31/5377 ,  A61K31/5386 ,  A61K31/551 ,  C07D413/14 ,  C07D417/14 ,  C07D498/10

Abstract: The present disclosure relates to bifunctional compounds, which find utility as modulators of SMARCA2 or BRM (target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a ligand that binds to the Von Hippel-Lindau 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：US11981683B2

公开(公告)日：2024-05-14

申请号：US17699082

申请日：2022-03-19

Applicant: Arvinas Operations, Inc.

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

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

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

Abstract: 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：US20240091204A1

公开(公告)日：2024-03-21

申请号：US18309867

申请日：2023-09-18

Applicant: Arvinas Operations, Inc.

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

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

CPC classification number: A61K31/427 ,  A61K31/4035 ,  A61K31/4245 ,  A61K31/437 ,  A61K31/4439 ,  A61K31/496 ,  A61K31/541 ,  A61K47/555

Abstract: 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

Applicant: Arvinas Operations, Inc.

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

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

CPC classification number: A61K31/427 ,  A61K31/4035 ,  A61K31/4245 ,  A61K31/437 ,  A61K31/4439 ,  A61K31/496 ,  A61K31/541 ,  A61K47/555

Abstract: 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

Applicant: Arvinas Operations, Inc. ,  Yale University

Inventor： 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: C07D471/04 ,  C07D417/14 ,  A61K45/06 ,  C07D417/12 ,  C07D403/06 ,  C07D403/14 ,  C07D401/14 ,  C07D413/14 ,  C07D405/14 ,  C07D495/04

CPC classification number: C07D471/04 ,  A61K45/06 ,  C07D401/14 ,  C07D403/06 ,  C07D403/14 ,  C07D405/14 ,  C07D413/14 ,  C07D417/12 ,  C07D417/14 ,  C07D495/04

Abstract: 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.