公开(公告)号：US12053469B2

公开(公告)日：2024-08-06

申请号：US17207325

申请日：2021-03-19

Applicant: Arvinas Operations, Inc.

Inventor： Erika Araujo ,  Michael M. Berlin ,  Steven M. Sparks ,  Jing Wang ,  Wei Zhang

IPC: A61K31/506 ,  A61K31/496 ,  A61K31/5377 ,  A61K45/06 ,  A61P25/16 ,  C07D401/14 ,  C07D413/14 ,  C07D487/10

CPC classification number: A61K31/506 ,  A61K31/496 ,  A61K31/5377 ,  A61K45/06 ,  A61P25/16 ,  C07D401/14 ,  C07D413/14 ,  C07D487/10

Abstract: Bifunctional compounds, which find utility as modulators of leucine-rich repeat kinase 2 (LRRK2), are described herein. In particular, the hetero-bifunctional compounds of the present disclosure contain on one end a moiety that binds to the cereblon E3 ubiquitin ligase and on the other end a moiety which binds LRRK2, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The hetero-bifunctional compounds of the present disclosure exhibit a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aberrant regulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.

公开(公告)号：US12036209B2

公开(公告)日：2024-07-16

申请号：US17196695

申请日：2021-03-09

Applicant: Arvinas Operations, Inc.

Inventor： Andrew P. Crew ,  Erika Araujo

IPC: A61K31/437 ,  A61K31/422 ,  A61K31/427 ,  A61K31/551 ,  A61K38/20 ,  A61K38/53 ,  A61K47/64 ,  A61P21/04 ,  A61P25/00 ,  A61P29/00 ,  A61P35/00 ,  A61P37/06 ,  C07D401/14 ,  C07D417/14 ,  C07D487/04

CPC classification number: A61K31/437 ,  A61K31/422 ,  A61K31/427 ,  A61K31/551 ,  A61K38/2006 ,  A61K38/53 ,  A61K47/642 ,  A61P21/04 ,  A61P25/00 ,  A61P29/00 ,  A61P35/00 ,  A61P37/06 ,  C07D401/14 ,  C07D417/14 ,  C07D487/04

Abstract: The present disclosure relates to bifunctional compounds, which find utility as modulators of Interleukin-1 Receptor-Associated Kinase 4 (IRAK-4); the target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a Von Hippel-Lindau, cereblon, ligand which binds to the 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：US11858940B2

公开(公告)日：2024-01-02

申请号：US17207330

申请日：2021-03-19

Applicant: Arvinas Operations, Inc.

Inventor： Erika Araujo ,  Michael Berlin ,  Steven M. Sparks ,  Jing Wang ,  Wei Zhang

IPC: C07D487/04 ,  A61K45/06 ,  C07D519/00

CPC classification number: C07D487/04 ,  A61K45/06 ,  C07D519/00

Abstract: Bifunctional compounds, which find utility as modulators of non-receptor Leucine-rich repeat kinase 2 (LRRK2), are described herein. In particular, the bifunctional compounds of the present disclosure contain on one end a moiety that binds to the cereblon E3 ubiquitin ligase and on the other end a moiety which binds LRRK2, 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 exhibit a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aberrant regulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.

公开(公告)号：US20220331297A1

公开(公告)日：2022-10-20

申请号：US17196695

申请日：2021-03-09

Applicant: Arvinas Operations, Inc.

Inventor： Andrew P. Crew ,  Erika Araujo

IPC: A61K31/437 ,  A61P25/00 ,  C07D487/04 ,  C07D417/14 ,  A61P29/00 ,  C07D401/14 ,  A61K47/64 ,  A61P21/04 ,  A61P37/06 ,  A61P35/00 ,  A61K31/422 ,  A61K31/427 ,  A61K31/551 ,  A61K38/20 ,  A61K38/53

Abstract: The present disclosure relates to bifunctional compounds, which find utility as modulators of Interleukin-1 Receptor-Associated Kinase 4 (IRAK-4); the target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a Von Hppel-Lindau, cereblon, ligand which binds to the 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：US11065231B2

公开(公告)日：2021-07-20

申请号：US16194094

申请日：2018-11-16

Applicant: Arvinas Operations, Inc.

Inventor： Andrew P. Crew ,  Erika Araujo

IPC: A61K31/437 ,  A61P25/00 ,  C07D487/04 ,  C07D417/14 ,  A61P29/00 ,  C07D401/14 ,  A61K47/64 ,  A61P21/04 ,  A61P37/06 ,  A61P35/00 ,  A61K31/422 ,  A61K31/427 ,  A61K31/551 ,  A61K38/20 ,  A61K38/53

Abstract: The present disclosure relates to bifunctional compounds, which find utility as modulators of Interleukin-1 Receptor-Associated Kinase 4 (IRAK-4); the target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a Von Hppel-Lindau, cereblon, ligand which binds to the 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：US20220064168A1

公开(公告)日：2022-03-03

申请号：US17207330

申请日：2021-03-19

Applicant: Arvinas Operations, Inc.

Inventor： Erika Araujo ,  Michael Berlin ,  Steven M. Sparks ,  Jing Wang ,  Wei Zhang

IPC: C07D487/04 ,  C07D519/00 ,  A61K45/06

Abstract: Bifunctional compounds, which find utility as modulators of non-receptor Leucine-rich repeat kinase 2 (LRRK2), are described herein. In particular, the bifunctional compounds of the present disclosure contain on one end a moiety that binds to the cereblon E3 ubiquitin ligase and on the other end a moiety which binds LRRK2, 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 exhibit a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aberrant regulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.

公开(公告)号：US20210315896A1

公开(公告)日：2021-10-14

申请号：US17207325

申请日：2021-03-19

Applicant: Arvinas Operations, Inc.

Inventor： Erika Araujo ,  Michael M. Berlin ,  Steven M. Sparks ,  Jing Wang ,  Wei Zhang

IPC: A61K31/506 ,  A61K45/06 ,  C07D401/14 ,  C07D487/10 ,  A61K31/496 ,  C07D413/14 ,  A61K31/5377 ,  A61P25/16

Abstract: Bifunctional compounds, which find utility as modulators of leucine-rich repeat kinase 2 (LRRK2), are described herein. In particular, the hetero-bifunctional compounds of the present disclosure contain on one end a moiety that binds to the cereblon E3 ubiquitin ligase and on the other end a moiety which binds LRRK2, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The hetero-bifunctional compounds of the present disclosure exhibit a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aberrant regulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.