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.

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：US20240382599A1

公开(公告)日：2024-11-21

申请号：US18623722

申请日：2024-04-01

Applicant: Arvinas Operations, Inc. ,  Yale University

Inventor： Andrew P. Crew ,  Kurt Zimmermann ,  Jing Wang ,  Michael Berlin ,  Hanqing Dong ,  Alexey Ishchenko ,  Yimin Qian ,  Saul Jaime-Figueroa ,  George Burslem ,  Craig M. Crews

IPC: A61K47/54 ,  A61K31/427 ,  A61K31/454 ,  A61K31/496 ,  A61K31/506 ,  A61K31/517 ,  A61K31/519 ,  A61K31/52 ,  A61K31/55 ,  A61K31/551 ,  A61K38/07 ,  A61K45/06 ,  A61K47/55 ,  C07D471/04

Abstract: 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：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：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：US12171831B2

公开(公告)日：2024-12-24

申请号：US18052096

申请日：2022-11-02

Applicant: Arvinas Operations, Inc. ,  YALE UNIVERSITY

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

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

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：US20210187108A1

公开(公告)日：2021-06-24

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: 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：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：US20220267305A1

公开(公告)日：2022-08-25

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

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

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：US20190192514A1

公开(公告)日：2019-06-27

申请号：US16284790

申请日：2019-02-25

Applicant: Arvinas Operations, Inc.

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

IPC: A61K31/506 ,  C07K5/062 ,  C07D417/04 ,  A61K45/06 ,  C07D413/04 ,  A61K47/66

CPC classification number: A61K31/506 ,  A61K45/06 ,  A61K47/665 ,  A61K2300/00 ,  C07D413/04 ,  C07D417/04 ,  C07K5/06034

Abstract: 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.