公开(公告)号：US20230082997A1

公开(公告)日：2023-03-16

申请号：US17571018

申请日：2022-01-07

Applicant: Arvinas Operations, Inc.

Inventor： Michael BERLIN ,  Andrew P. CREW ,  Craig M. CREWS ,  Hanqing DONG ,  Keith R. HORNBERGER ,  Yimin QIAN ,  Lawrence B. SNYDER ,  Jing WANG ,  Kurt ZIMMERMANN

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

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：US20250034096A1

公开(公告)日：2025-01-30

申请号：US18772066

申请日：2024-07-12

Applicant: Arvinas Operations, Inc.

Inventor： Michael BERLIN ,  Andrew P. CREW ,  Craig M. CREWS ,  Hanqing DONG ,  Keith R. HORNBERGER ,  Lawrence B. SNYDER ,  Jing WANG ,  Kurt ZIMMERMANN

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

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：US20230263893A1

公开(公告)日：2023-08-24

申请号：US18052096

申请日：2022-11-02

Applicant: ARVINAS OPERATIONS, INC. ,  YALE UNIVERISTY

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

CPC classification number: 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：US20210009528A1

公开(公告)日：2021-01-14

申请号：US16938864

申请日：2020-07-24

Applicant: Arvinas Operations, Inc.

Inventor： Andrew P. CREW ,  Keith R. HORNBERGER ,  Kurt ZIMMERMANN ,  Jing WANG ,  Michael BERLIN ,  Craig M. CREWS ,  Hanqing DONG ,  Lawrence B. SNYDER

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 ,  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.

公开(公告)号：US20240217962A1

公开(公告)日：2024-07-04

申请号：US18486668

申请日：2023-10-13

Applicant: Arvinas Operations, Inc.

Inventor： Andrew P. CREW ,  Michael BERLIN ,  Angela M. CACACE ,  Julian T. CHANDLER

IPC: C07D417/14 ,  A61K45/06 ,  A61K47/54 ,  C07D401/04 ,  C07D487/04

CPC classification number: C07D417/14 ,  A61K47/54 ,  C07D401/04 ,  C07D487/04 ,  A61K45/06

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：US20230183209A1

公开(公告)日：2023-06-15

申请号：US18079790

申请日：2022-12-12

Applicant: Arvinas Operations, Inc.

Inventor： Andrew P. CREW ,  Michael BERLIN ,  Keith R. HORNBERGER ,  Lawrence B. SNYDER ,  Jing WANG ,  Yimin QIAN ,  Hanqing DONG ,  Kurt ZIMMERMANN

IPC: C07D401/14 ,  C07D417/14 ,  C07D471/04 ,  A61P35/02 ,  C07D487/04 ,  C07D495/14 ,  C07D498/04 ,  C07D471/10

CPC classification number: C07D401/14 ,  C07D417/14 ,  C07D471/04 ,  A61P35/02 ,  C07D487/04 ,  C07D495/14 ,  C07D498/04 ,  C07D471/10

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：US20220259154A1

公开(公告)日：2022-08-18

申请号：US17539679

申请日：2021-12-01

Applicant: Arvinas Operations, Inc.

Inventor： Michael BERLIN ,  Andrew P. CREW ,  Craig M. CREWS ,  Hanqing DONG ,  Keith R. HORNBERGER ,  Lawrence B. SNYDER ,  Jing WANG ,  Kurt ZIMMERMANN

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 ,  A61K31/506 ,  A61K31/496 ,  A61K31/501 ,  C07D401/04

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：US20240059686A1

公开(公告)日：2024-02-22

申请号：US18085500

申请日：2022-12-20

Applicant: Arvinas Operations, Inc.

Inventor： Andrew P. CREW ,  Hanqing DONG ,  Jing WANG ,  Xin CHEN ,  Yimin QIAN ,  Craig M. CREWS ,  Michael BERLIN ,  Meizhong JIN

IPC: C07D417/14 ,  C07D413/14 ,  C07D417/12 ,  C07D413/12 ,  C07D233/86 ,  C07D401/04 ,  C07D491/107 ,  C07D471/10 ,  A61K45/06 ,  C07K5/078 ,  A61P35/00 ,  A61P25/28

CPC classification number: C07D417/14 ,  C07D413/14 ,  C07D417/12 ,  C07D413/12 ,  C07D233/86 ,  A61P25/28 ,  C07D491/107 ,  C07D471/10 ,  A61K45/06 ,  C07K5/06165 ,  A61P35/00 ,  C07D401/04

Abstract: The present invention 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：US20230331681A1

公开(公告)日：2023-10-19

申请号：US18213055

申请日：2023-06-22

Applicant: Arvinas Operations, Inc.

Inventor： Michael BERLIN ,  Andrew P. CREW ,  Craig M. CREWS ,  Hanqing DONG ,  Keith R. HORNBERGER ,  Lawrence B. SNYDER ,  Jing WANG ,  Kurt ZIMMERMANN

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 ,  A61K31/506 ,  A61K31/496 ,  A61K31/501 ,  C07D401/04

CPC classification number: 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 ,  C07D401/04

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.