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：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：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：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.

公开(公告)号：US20230099344A1

公开(公告)日：2023-03-30

申请号：US17807094

申请日：2022-06-15

Applicant: Arvinas Operations, Inc.

Inventor： Erika Marina Vieira ARAUJO ,  Jennifer L. CANTLEY ,  Keith R. HORNBERGER ,  Jesus Raul MEDINA

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

Abstract: This application relates to a bifunctional compound having the structure of Formula (I): or a pharmaceutically acceptable salt, solvate, enantiomer, stereoisomer, or isotopic derivative thereof, which contains, on one end, a cereblon E3 ubiquitin ligase that binds to the E3 ubiquitin ligase and, on the other end, a moiety that binds the target protein, Interleukin-1 Receptor-Associated Kinase 4 (IRAK-4), 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 present disclosure exhibit a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from cellular signaling mediated by the target protein are treated or prevented with bifunctional compounds and compositions of the present disclosure.