公开(公告)号：US20210040044A1

公开(公告)日：2021-02-11

申请号：US17006193

申请日：2020-08-28

Applicant: Arvinas Operations, Inc.

Inventor： Andrew P. Crew ,  Keith R. Hornberger ,  Lawrence B. Snyder ,  Kurt Zimmermann ,  Jing Wang ,  Michael Berlin ,  Hanqing Dong

IPC: C07D233/42 ,  C07D221/20 ,  C07D211/76 ,  C07D205/04 ,  C07D239/24 ,  A61K45/06 ,  C07D209/48 ,  C07D237/08 ,  C07D213/72 ,  A61K31/02 ,  C07D401/14 ,  A61K31/166 ,  A61K31/277 ,  C07D231/12 ,  C07D241/04 ,  A61K31/497 ,  A61K47/10

Abstract: The present disclosure relates to bifunctional compounds, which find utility to degrade and (inhibit) Androgen Receptor. In particular, the present disclosure is directed to compounds, which contain on one end a cereblon ligand which binds to the E3 ubiquitin ligase and on the other end a moiety which binds Androgen Receptor, such that Androgen Receptor is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of Androgen Receptor. The present disclosure exhibits a broad range of pharmacological activities associated with compounds according to the present disclosure, consistent with the degradation/inhibition of Androgen Receptor.

公开(公告)号：US10899742B1

公开(公告)日：2021-01-26

申请号：US16744414

申请日：2020-01-16

Applicant: Arvinas Operations, Inc.

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

IPC: A61K31/496 ,  C07D401/14 ,  A61K47/54 ,  A61P15/00 ,  A61P35/00 ,  A61K31/454 ,  A61K31/4545 ,  A61K31/4725 ,  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：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：US20240360152A1

公开(公告)日：2024-10-31

申请号：US18659374

申请日：2024-05-09

Applicant: Arvinas Operations, Inc.

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

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

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：US20240325547A1

公开(公告)日：2024-10-03

申请号：US18610001

申请日：2024-03-19

Applicant: Arvinas Operations, Inc.

Inventor： MICHAEL BERLIN ,  Hanqing Dong ,  Dan Sherman ,  Lawrence B. Snyder ,  Jing Wang ,  Wei Zhang

IPC: A61K47/55 ,  A61K45/06 ,  A61K47/54 ,  A61P35/00

CPC classification number: A61K47/55 ,  A61K45/06 ,  A61K47/545 ,  A61P35/00

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 cereblon 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：US20230086457A1

公开(公告)日：2023-03-23

申请号：US17724987

申请日：2022-04-20

Applicant: ARVINAS OPERATIONS, INC.

Inventor： Michael Berlin ,  Andrew P. Crew ,  Hanqing Dong ,  John J. Flanagan

IPC: A61K31/4166 ,  A61K31/381 ,  A61K31/495 ,  C07D401/04 ,  C07D401/14 ,  C07D417/14

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：US20220315575A1

公开(公告)日：2022-10-06

申请号：US16932590

申请日：2020-07-17

Applicant: Arvinas Operations, Inc.

Inventor： Andrew P. Crew ,  Michael Berlin ,  Hanqing Dong ,  Alexey Ishchenko ,  Angela M. Cacace ,  Julian T. Chandler

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

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：US11427548B2

公开(公告)日：2022-08-30

申请号：US16656526

申请日：2019-10-17

Applicant: Arvinas Operations, Inc.

Inventor： Andrew P. Crew ,  Hanqing Dong ,  Jing Wang ,  Xin Chen ,  Yimin Qian ,  Kurt Zimmermann ,  Michael Berlin ,  Lawrence Snyder

IPC: C07D233/86 ,  C07D417/14 ,  C07D413/12 ,  C07D417/12 ,  A61K45/06 ,  C07D491/107 ,  C07D471/10 ,  C07D235/02 ,  C07D401/04 ,  C07D401/08 ,  C07C255/54 ,  C07D237/24 ,  C07C271/24 ,  C07D241/28 ,  C07D239/42 ,  C07D231/14 ,  C07D213/82 ,  A61K31/4166 ,  A61K47/54 ,  A61K31/4439 ,  A61K31/4188 ,  A61K31/435 ,  A61K31/454 ,  A61K31/4184 ,  A61K31/277 ,  C07D413/14

Abstract: The present disclosure relates to bifunctional compounds, which find utility to degrade (and inhibit) Androgen Receptor. 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 Androgen Receptor such that Androgen Receptor is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of Androgen Receptor. The present invention exhibits a broad range of pharmacological activities associated with compounds according to the present invention, consistent with the degradation/inhibition of Androgen Receptor.

公开(公告)号：US20220162163A1

公开(公告)日：2022-05-26

申请号：US17569145

申请日：2022-01-05

Applicant: Arvinas Operations, Inc.

Inventor： Michael Berlin ,  Andrew P. Crew ,  Hanqing Dong ,  Yimin Qian

IPC: C07D207/16 ,  C07D417/14 ,  C07D403/04 ,  C07D417/04 ,  A61K47/55 ,  C07D401/04 ,  C07D495/14 ,  C07D405/14 ,  A61K31/40 ,  A61K31/4178 ,  A61K31/4439 ,  A61K31/444 ,  A61K31/496 ,  A61K31/506 ,  A61K31/551 ,  A61K45/06 ,  C07D403/12 ,  C07D471/04 ,  C07D487/14 ,  C07D519/00

Abstract: The description relates to Inhibitors of Apoptosis Proteins (IAPs) 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 invention. In particular, the description provides compounds, which contain on one end a ligand which binds to the IAP 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：US11236051B2

公开(公告)日：2022-02-01

申请号：US16938864

申请日：2020-07-24

Applicant: Arvinas Operations, Inc.

Inventor： Andrew P. Crew ,  Kurt Zimmermann ,  Hanqing Dong ,  Lawrence B. Snyder

IPC: C07D401/04 ,  C07D233/42 ,  A61K31/166 ,  C07D211/76 ,  C07D241/04 ,  C07D231/12 ,  C07D213/72 ,  C07D205/04 ,  C07D237/08 ,  C07D239/24 ,  C07D221/20 ,  A61K31/277 ,  A61K47/10 ,  A61K31/02 ,  A61K31/497 ,  C07D209/48 ,  C07D401/14 ,  A61K45/06 ,  A61K31/506 ,  A61K31/496 ,  A61K31/501

Abstract: The present disclosure relates to bifunctional compounds, which find utility to degrade (and inhibit) Androgen Receptor. In particular, the present disclosure is directed to compounds, which contain on one end a cereblon ligand which binds to the E3 ubiquitin ligase and on the other end a moiety which binds Androgen Receptor, such that Androgen Receptor is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of Androgen Receptor. The present disclosure exhibits a broad range of pharmacological activities associated with compounds according to the present disclosure, consistent with the degradation/inhibition of Androgen Receptor.