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：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：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.

公开(公告)号：US20210315856A1

公开(公告)日：2021-10-14

申请号：US17356751

申请日：2021-06-24

Applicant: Arvinas Operations, Inc.

Inventor： Andrew P. Crew ,  Hanging Dong ,  Brain Hamman ,  Taavi K. Neklesa ,  Yimin Qian ,  Jing Wang ,  Kurt Zimmermann

IPC: A61K31/277 ,  G16B20/00 ,  A61K47/55 ,  G16C20/50 ,  G16B15/30 ,  G16B20/30 ,  A61K31/4166 ,  A61K31/551 ,  A61K38/05 ,  G01N33/68

Abstract: The present disclosure is based on the surprising and unexpected discovery that a ligand molecule with certain characteristics is able to bind to two protein molecules simultaneously and recruit them to form a transient or stable protein-protein interaction complex. The protein-protein interaction and other cross-domain interactions gained in this process contribute additional stabilization energy to the complex beyond the combination of the binary binding energies, and therefore, largely increase the binding potency of the ligand. Accordingly, the present disclosure provides a Protein-Protein Interaction Inducing Technology (PPIIT), which includes a method to design and identify the tripartite or bifunctional compounds and use such compounds to induce protein-protein interactions in various contexts. The present disclosure also provides a composition for the purpose of inducing protein-protein interactions.

公开(公告)号：US20200155690A1

公开(公告)日：2020-05-21

申请号：US16751158

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：US20200055825A1

公开(公告)日：2020-02-20

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 ,  Craig M. Crews ,  Michael Berlin ,  Lawrence Snyder

IPC: C07D233/86 ,  C07D417/14 ,  C07D413/12 ,  C07D417/12 ,  C07D413/14 ,  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

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.