公开(公告)号：US10723717B2

公开(公告)日：2020-07-28

申请号：US15853166

申请日：2017-12-22

Applicant: Arvinas, Inc. ,  Yale University

Inventor： Andrew P. Crew ,  Keith R. Hornberger ,  Jing Wang ,  Hanqing Dong ,  Yimin Qian ,  Craig M. Crews ,  Saul Jaime-Figueroa

IPC: C07D519/00 ,  C07D401/14 ,  C07D401/04 ,  A61K31/4439 ,  C07D417/14 ,  A61K31/4545 ,  C07D487/04 ,  A61P9/00 ,  C07D471/04 ,  A61K31/437 ,  A61K45/06 ,  A61P35/00 ,  A61P43/00 ,  A61P25/00 ,  A61K31/4188 ,  A61K47/54 ,  A61K47/55

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：US20180155322A1

公开(公告)日：2018-06-07

申请号：US15829541

申请日：2017-12-01

Applicant: Arvinas, Inc.

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

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

CPC classification number: C07D401/14 ,  A61K31/454 ,  A61K31/4545 ,  A61K31/4725 ,  A61K31/496 ,  A61K31/497 ,  A61K31/501 ,  A61K31/519 ,  A61K31/5386 ,  A61K31/551 ,  A61K38/05 ,  A61K38/06 ,  A61K45/06 ,  A61K47/54 ,  A61K47/545 ,  A61P15/00 ,  A61P35/00 ,  C07D401/04 ,  C07D471/04 ,  C07D471/10 ,  C07D487/04 ,  C07D487/08 ,  C07D487/10 ,  C07D498/10 ,  C07K5/06034 ,  C07K5/06165 ,  C07K5/0806

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：US20180147202A1

公开(公告)日：2018-05-31

申请号：US15574770

申请日：2016-06-06

Applicant: Arvinas, Inc.

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

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

CPC classification number: A61K31/506 ,  A61K45/06 ,  A61K47/665 ,  A61K2300/00 ,  C07D413/04 ,  C07D417/04 ,  C07K5/06034

Abstract: The present invention relates to bifunctional compounds, which find utility to degrade and (inhibit) TBK 1. 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：US20180099940A1

公开(公告)日：2018-04-12

申请号：US15730728

申请日：2017-10-11

Applicant: Arvinas, 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 ,  C07D209/48 ,  C07D211/76 ,  C07D241/04 ,  C07D231/12 ,  C07D213/72 ,  C07D205/04 ,  C07D237/08 ,  C07D239/24 ,  C07D221/20 ,  A61K31/277 ,  A61K47/10 ,  A61K31/02 ,  A61K31/497 ,  A61K31/166

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：US20180237418A1

公开(公告)日：2018-08-23

申请号：US15881318

申请日：2018-01-26

Applicant: Arvinas, Inc.

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

IPC: C07D401/14 ,  C07D471/04 ,  C07D409/12 ,  C07D403/06 ,  C07D403/14 ,  C07D405/14 ,  C07D413/14 ,  C07D417/12 ,  C07D417/14 ,  A61P35/00

CPC classification number: C07D401/14 ,  A61P35/00 ,  C07D403/06 ,  C07D403/14 ,  C07D405/14 ,  C07D409/12 ,  C07D413/14 ,  C07D417/12 ,  C07D417/14 ,  C07D471/04

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 a cereblon, Von Hippel-Lindau ligase-binding moiety, 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：US20180193470A1

公开(公告)日：2018-07-12

申请号：US15852854

申请日：2017-12-22

Applicant: Arvinas, Inc. ,  Yale University

Inventor： Andrew P. Crew ,  Kurt Zimmermann ,  Jing Wang ,  Michael Berlin ,  Hanqing Dong ,  Alexey Ishchenko ,  Yimin Qian ,  Craig M. Crews ,  Saul Jaime-Figueroa ,  George Burslem

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

Abstract: The present disclosure relates to bifunctional compounds, which find utility as modulators of receptor tyrosine kinase (RTK) proteins. In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a ligand which binds to an 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 effectuate ubiquitination, and therefore, degradation (and inhibition) of the 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：US20170327469A1

公开(公告)日：2017-11-16

申请号：US15663273

申请日：2017-07-28

Applicant: Arvinas, Inc.

Inventor： Andrew P. Crew ,  Hanqing Dong ,  Jing Wang ,  Caterina Ferraro ,  Xin Chen ,  Yimin Qian

IPC: C07D233/86 ,  C07D471/10 ,  C07D401/08 ,  C07D401/04 ,  C07D241/28 ,  C07D239/42 ,  C07D237/24 ,  C07D235/02 ,  C07D231/14 ,  C07D213/82 ,  C07C271/24 ,  C07C255/54 ,  A61K45/06 ,  A61K31/454 ,  A61K31/4439 ,  A61K31/435 ,  A61K31/4188 ,  A61K31/4184 ,  A61K31/4166 ,  A61K31/277 ,  A61K47/54 ,  C07D491/107 ,  C07C2601/04

CPC classification number: C07D233/86 ,  A61K31/277 ,  A61K31/4166 ,  A61K31/4184 ,  A61K31/4188 ,  A61K31/435 ,  A61K31/4439 ,  A61K31/454 ,  A61K45/06 ,  A61K47/545 ,  C07C255/54 ,  C07C271/24 ,  C07C2601/04 ,  C07D213/82 ,  C07D231/14 ,  C07D235/02 ,  C07D237/24 ,  C07D239/42 ,  C07D241/28 ,  C07D401/04 ,  C07D401/08 ,  C07D413/12 ,  C07D413/14 ,  C07D417/12 ,  C07D417/14 ,  C07D471/10 ,  C07D491/107

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：US11352351B2

公开(公告)日：2022-06-07

申请号：US15002303

申请日：2016-01-20

Applicant: Arvinas, Inc.

Inventor： Meizhong Jin ,  Andrew P. Crew ,  Hanqing Dong ,  Jing Wang ,  Xin Chen ,  Yimin Qian

IPC: C07D417/14 ,  C07D413/14 ,  A61K31/422 ,  A61K31/4439 ,  C07D417/12 ,  A61K45/06 ,  A61K31/4545 ,  C07D233/86 ,  C07D401/04 ,  C07D491/107 ,  C07D471/10 ,  A61K31/427 ,  C07D413/12 ,  C07K5/078 ,  A61P35/00 ,  A61P25/28

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：US20180346461A1

公开(公告)日：2018-12-06

申请号：US16048191

申请日：2018-07-27

Applicant: Arvinas, Inc.

Inventor： Andrew P. Crew ,  Hanqing Dong ,  Jing Wang ,  Xin Chen ,  Yimin Qian ,  Kurt Zimmermann ,  Craig M. Crews ,  Michael Berlin ,  Lawrence Snyder

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

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

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：US10071164B2

公开(公告)日：2018-09-11

申请号：US14822309

申请日：2015-08-10

Applicant: Yale University ,  Arvinas, Inc.

Inventor： Andrew Crew ,  Craig Crews ,  Hanqing Dong ,  Eunhwa Ko ,  Jing Wang

IPC: C07K5/062 ,  C07K5/097 ,  A61K45/06 ,  A61K31/427 ,  A61K31/426 ,  A61K38/00 ,  A61K47/48

CPC classification number: A61K47/55 ,  A61K31/426 ,  A61K31/427 ,  A61K38/00 ,  A61K45/06 ,  A61K47/545 ,  A61K47/551 ,  C07K5/06026 ,  C07K5/06034 ,  C07K5/06052 ,  C07K5/0821

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.