公开(公告)号：US20220395576A1

公开(公告)日：2022-12-15

申请号：US17721916

申请日：2022-04-15

Applicant: Arvinas Operations, Inc.

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

IPC: A61K47/55 ,  A61K47/54 ,  A61K45/06 ,  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：US20220388984A1

公开(公告)日：2022-12-08

申请号：US17359424

申请日：2021-06-25

Applicant: Arvinas Operations, Inc.

Inventor： Andrew P. Crew ,  Hanqing Dong ,  Keith R. Hornberger ,  Yimin Quian ,  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

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：US20220378726A1

公开(公告)日：2022-12-01

申请号：US17354941

申请日：2021-06-22

Applicant: Arvinas Operations, Inc.

Inventor： Andrew P. Crew ,  Lawrence B. Snyder ,  Jing Wang ,  Hanqing Dong ,  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：US20210220475A1

公开(公告)日：2021-07-22

申请号：US17192083

申请日：2021-03-04

Applicant: Arvinas Operations, Inc. ,  Yale University

Inventor： Andrew P. Crew ,  Kurt Zimmermann ,  Jing Wang ,  Craig M. Crews ,  Saul Jaime-Figueroa ,  George Burslem

IPC: A61K47/54 ,  A61K47/55 ,  A61K31/519 ,  A61K31/427 ,  A61K31/454 ,  A61K31/517 ,  A61K31/55 ,  A61K31/496 ,  A61K31/551 ,  A61K45/06 ,  A61K38/07 ,  A61K31/52 ,  A61K31/506 ,  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：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：US20210171470A1

公开(公告)日：2021-06-10

申请号：US16888484

申请日：2020-05-29

Applicant: Arvinas Operations, Inc.

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

IPC: 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

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：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：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.