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：US11161841B2

公开(公告)日：2021-11-02

申请号：US16375643

申请日：2019-04-04

Applicant: Arvinas Operations, Inc.

Inventor： Andrew P. Crew ,  Keith R. Hornberger ,  Jing Wang ,  Hanqing Dong

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

Abstract: 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：US20210040081A1

公开(公告)日：2021-02-11

申请号：US17082839

申请日：2020-10-28

Applicant: Arvinas Operations, Inc.

Inventor： Andrew P. Crew ,  Yimin Qian ,  Hanqing Dong ,  Jing Wang

IPC: C07D417/14 ,  C07K5/062 ,  C07D403/12 ,  C07D403/14 ,  C07D413/14

Abstract: The present disclosure relates to compounds and a pharmaceutically acceptable salt thereof, compositions, combinations and medicaments containing the compounds, and processes for their preparation. The disclosure also relates to the use of the compounds, combinations, compositions and medicaments, for example as inhibitors of the activity of the estrogen receptor, including degrading the estrogen receptor, the treatment of diseases and conditions mediated by the estrogen receptor.

公开(公告)号：US12275716B2

公开(公告)日：2025-04-15

申请号：US17727386

申请日：2022-04-22

Applicant: Arvinas Operations, Inc.

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

IPC: C07D401/14 ,  A61P35/00 ,  C07D403/06 ,  C07D403/14 ,  C07D405/14 ,  C07D409/12 ,  C07D413/14 ,  C07D417/12 ,  C07D417/14 ,  C07D471/04

Abstract: 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：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：US12053469B2

公开(公告)日：2024-08-06

申请号：US17207325

申请日：2021-03-19

Applicant: Arvinas Operations, Inc.

Inventor： Erika Araujo ,  Michael M. Berlin ,  Steven M. Sparks ,  Jing Wang ,  Wei Zhang

IPC: A61K31/506 ,  A61K31/496 ,  A61K31/5377 ,  A61K45/06 ,  A61P25/16 ,  C07D401/14 ,  C07D413/14 ,  C07D487/10

CPC classification number: A61K31/506 ,  A61K31/496 ,  A61K31/5377 ,  A61K45/06 ,  A61P25/16 ,  C07D401/14 ,  C07D413/14 ,  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：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：US20240131023A1

公开(公告)日：2024-04-25

申请号：US18460063

申请日：2023-09-01

Applicant: Arvinas Operations, Inc.

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

IPC: 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 classification number: 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

Abstract: 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：US20230081501A1

公开(公告)日：2023-03-16

申请号：US17459179

申请日：2021-08-27

Applicant: Arvinas Operations, Inc.

Inventor： Keith R. Hornberger ,  Lawrence B. Snyder ,  Jing Wang

IPC: A61K31/454 ,  A61K47/55 ,  A61K31/437 ,  A61K47/54 ,  A61K31/4545 ,  A61K31/496 ,  A61K31/45

Abstract: Bifunctional compounds, which find utility as modulators of Rapidly Accelerated Fibrosarcoma (Raf, such as c-Raf, A-Raf, and/or B-Raf), 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 Raf, 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.