公开(公告)号：US11173211B2

公开(公告)日：2021-11-16

申请号：US16563842

申请日：2019-09-07

Applicant: ARVINAS OPERATIONS, INC. ,  YALE UNIVERSITY

Inventor： Andrew P. Crew ,  Keith R. Hornberger ,  Jing Wang ,  Saul Jaime-Figueroa ,  Hanqing Dong

IPC: C07D401/14 ,  C07D471/04 ,  A61K31/437 ,  A61P35/00 ,  A61K47/55 ,  C07D519/00 ,  C07D417/14 ,  C07D413/14

Abstract: The present disclosure relates to bifunctional compounds, which find utility as modulators of Rapidly Accelerated Fibrosarcoma (RAF, such as c-RAF, A-RAF and/or B-RAF; the 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 RAF, 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, or the constitutive activation of the target protein, are treated or prevented with compounds and compositions of the present disclosure.

公开(公告)号：US11104666B2

公开(公告)日：2021-08-31

申请号：US16889490

申请日：2020-06-01

Applicant: Arvinas Operations, Inc.

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

IPC: C07D401/14 ,  C07D471/04 ,  C07D487/10 ,  C07D471/10 ,  C07D487/04 ,  C07D487/08 ,  C07D498/10 ,  C07D401/04 ,  A61P15/00 ,  A61K31/496 ,  A61K31/4545 ,  A61K38/06 ,  A61P35/00 ,  A61K31/5386 ,  A61K38/05 ,  C07K5/083 ,  A61K31/497 ,  A61K47/54 ,  A61K45/06 ,  A61K31/454 ,  C07K5/078 ,  A61K31/501 ,  A61K31/519 ,  A61K31/4725 ,  A61K31/551 ,  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：US20210145832A1

公开(公告)日：2021-05-20

申请号：US17159674

申请日：2021-01-27

Applicant: Arvinas Operations, Inc.

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

IPC: A61K31/506 ,  A61K45/06 ,  A61K47/66 ,  C07D413/04 ,  C07D417/04 ,  C07K5/062

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：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.

公开(公告)号：US20190233408A1

公开(公告)日：2019-08-01

申请号：US16376225

申请日：2019-04-05

Applicant: Arvinas Operations, Inc.

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

IPC: C07D417/14 ,  C07D413/14 ,  C07D403/12 ,  C07D403/14

CPC classification number: C07D417/14 ,  C07D403/12 ,  C07D403/14 ,  C07D413/14

Abstract: The present disclosure relates to compounds and a pharmaceutically acceptable salt thereof, compositions, combinations and medicaments containing the compounds, and processes for their preparation. The disclosure also relates to the use of the compounds, combinations, compositions and medicaments, for example as inhibitors of the activity of the estrogen receptor, including degrading the estrogen receptor, the treatment of diseases and conditions mediated by the estrogen receptor.