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.

公开(公告)号：US10946017B2

公开(公告)日：2021-03-16

申请号：US16284790

申请日：2019-02-25

Applicant: Arvinas Operations, Inc.

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

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

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：US20200155689A1

公开(公告)日：2020-05-21

申请号：US16751154

申请日：2020-01-23

Applicant: ARVINAS OPERATIONS, INC.

Inventor： ANDREW P. CREW ,  Craig M. Crews ,  Hanqing Dong ,  Keith R. Hornberger ,  Jing Wang ,  Yimin Qian ,  Kurt Zimmermann ,  Michael Berlin ,  Lawrence B. Snyder

IPC: A61K47/55 ,  A61K31/496 ,  A61K31/506 ,  A61K31/501 ,  A61K45/06 ,  A61K31/551 ,  A61K31/497 ,  A61K31/437 ,  C07D471/04 ,  C07D401/14 ,  C07D401/04 ,  A61P35/00 ,  A61K47/54

Abstract: The description relates to cereblon E3 ligase binding compounds, including bifunctional compounds comprising the same, 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 disclosure. In particular, the description provides compounds, which contain on one end a ligand which binds to the cereblon E3 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. Compounds can be synthesized that exhibit a broad range of pharmacological activities consistent with the degradation/inhibition of targeted polypeptides of nearly any type.

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：US20240299366A1

公开(公告)日：2024-09-12

申请号：US18456718

申请日：2023-08-28

Applicant: Arvinas Operations, Inc.

Inventor： Andrew P. CREW ,  Craig M. Crews ,  Hanqing Dong ,  Jing Wang ,  Yimin Qian ,  Meizhong Jin

IPC: A61K31/426 ,  A61K31/454 ,  A61K31/505 ,  A61K31/551 ,  A61K45/06 ,  A61K47/54 ,  A61K47/66 ,  C07D401/04 ,  C07D401/14 ,  C07D409/14 ,  C07D417/14 ,  C07D487/04 ,  C07D495/14 ,  C07D498/14 ,  C07K14/47 ,  C07K14/72 ,  C12N9/12 ,  C12N9/18 ,  C12Q1/25

CPC classification number: A61K31/426 ,  A61K31/454 ,  A61K31/505 ,  A61K31/551 ,  A61K45/06 ,  A61K47/545 ,  A61K47/555 ,  A61K47/66 ,  C07D401/04 ,  C07D401/14 ,  C07D409/14 ,  C07D417/14 ,  C07D487/04 ,  C07D495/14 ,  C07D498/14 ,  C07K14/4705 ,  C07K14/721 ,  C12N9/12 ,  C12N9/18 ,  C12Q1/25 ,  C12Y207/11001 ,  C12Y301/01031 ,  G01N2333/9015 ,  G01N2500/02

Abstract: The description relates to imide-based compounds, including bifunctional compounds comprising the same, 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 description provides compounds, which contain on one end a ligand which binds to the cereblon E3 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. Compounds can be synthesized that exhibit a broad range of pharmacological activities consistent with the degradation/inhibition of targeted polypeptides of nearly any type.