公开(公告)号：US12264157B2

公开(公告)日：2025-04-01

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: C07D521/00 ,  A61K31/422 ,  A61K31/437 ,  A61K31/4439 ,  A61K31/5377 ,  A61K45/06 ,  A61P35/00 ,  C07D207/16 ,  C07D207/26 ,  C07D401/06 ,  C07D401/10 ,  C07D401/14 ,  C07D403/06 ,  C07D403/14 ,  C07D405/06 ,  C07D405/12 ,  C07D405/14 ,  C07D413/06 ,  C07D413/12 ,  C07D413/14 ,  C07D417/12 ,  C07D417/14 ,  C07D471/04 ,  C07D471/12 ,  C07D471/14 ,  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：US12208095B2

公开(公告)日：2025-01-28

申请号：US17001519

申请日：2020-08-24

Applicant: Arvinas Operations, Inc.

Inventor： Andrew P. Crew ,  John Flanagan ,  Sheryl Maxine Gough ,  Royal J. Haskell, III ,  Marcia Dougan Moore ,  Yimin Qian ,  Ian Charles Anthony Taylor ,  Jing Wang

IPC: A61K31/496 ,  A61K31/519 ,  A61K47/02 ,  A61K47/22 ,  A61K47/26 ,  A61K47/38 ,  A61P35/00

Abstract: The present application relates to treating and/or preventing breast cancer, including locally advanced or metastatic, ER+, HER2− breast cancer, in a subject in need of treatment, comprising administering a compound of Formula (I), or a pharmaceutically acceptable salt, enantiomer, stereoisomer, solvate, polymorph, isotopic derivative, or prodrug thereof, wherein R1, R2, R3, R4, m, and n are defined herein.

公开(公告)号：US11858940B2

公开(公告)日：2024-01-02

申请号：US17207330

申请日：2021-03-19

Applicant: Arvinas Operations, Inc.

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

IPC: C07D487/04 ,  A61K45/06 ,  C07D519/00

CPC classification number: C07D487/04 ,  A61K45/06 ,  C07D519/00

Abstract: Bifunctional compounds, which find utility as modulators of non-receptor Leucine-rich repeat kinase 2 (LRRK2), are described herein. In particular, the 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 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：US20230097358A1

公开(公告)日：2023-03-30

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

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：US11597720B2

公开(公告)日：2023-03-07

申请号：US16932072

申请日：2020-07-17

Applicant: Arvinas Operations, Inc.

Inventor： Yimin Qian ,  Hanqing Dong ,  Jing Wang

IPC: C07D401/14 ,  A61K47/54 ,  A61P15/00 ,  A61P35/00 ,  A61K31/454 ,  A61K31/4545 ,  A61K31/4725 ,  A61K31/496 ,  A61K31/497 ,  A61K31/501 ,  A61K31/519 ,  A61K31/5386 ,  A61K31/551 ,  A61K38/05 ,  A61K38/06 ,  A61K45/06 ,  C07D401/04 ,  C07D471/04 ,  C07D471/10 ,  C07D487/04 ,  C07D487/08 ,  C07D487/10 ,  C07D498/10 ,  C07K5/078 ,  C07K5/083 ,  C07K5/062

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 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：US11554171B2

公开(公告)日：2023-01-17

申请号：US16912329

申请日：2020-06-25

Applicant: Arvinas Operations, Inc. ,  Yale University

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

IPC: A61P35/00 ,  A61K45/06 ,  C07D519/00 ,  C07D417/14 ,  C07D495/14 ,  A61K47/55

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：US20230000994A1

公开(公告)日：2023-01-05

申请号：US17387621

申请日：2021-07-28

Applicant: ARVINAS OPERATIONS, INC. ,  YALE UNIVERSITY

Inventor： Andrew P. Crew ,  Keith R. Hornberger ,  Jing Wang ,  Saul Jaime-Figueroa ,  Hanqing Dong ,  Lawrence B. Snyder

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

Abstract: 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

Applicant: Arvinas Operations, Inc. ,  Yale University

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

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

Abstract: 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：US20220323457A1

公开(公告)日：2022-10-13

申请号：US17073135

申请日：2020-10-16

Applicant: Arvinas Operations, Inc.

Inventor： Michael Berlin ,  Hanqing Dong ,  Dan Sherman ,  Lawrence Snyder ,  Jing Wang ,  Wei Zhang

IPC: A61K31/551 ,  A61K31/506 ,  C07D401/14 ,  C07D487/08 ,  A61K31/496 ,  C07D487/10 ,  C07D405/14 ,  C07D413/14 ,  A61K31/5355 ,  A61K31/5377 ,  A61K31/4985 ,  A61K31/55 ,  C07D487/04 ,  C07D417/14 ,  C07D471/10

Abstract: Bifunctional compounds, which find utility as modulators of B-cell lymphoma 6 protein (BCL6; target protein), are described herein. In particular, the bifunctional compounds of the present disclosure contain on one end a Von Hippel-Lindau, cereblon, Inhibitors of Apotosis Proteins or mouse double-minute homolog 2 ligand that 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 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 aggregation or accumulation 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

Applicant: Arvinas Operations, Inc.

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

IPC: 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

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 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.