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：US20210060008A1

公开(公告)日：2021-03-04

申请号：US17001519

申请日：2020-08-24

Applicant: Arvinas Operations, Inc.

Inventor： Xin CHEN ,  Andrew P. CREW ,  John FLANAGAN ,  Sheryl Maxine GOUGH ,  Royal J. HASKELL, III ,  Marcia Dougan MOORE ,  Yimin QIAN ,  Ian Charles Anthony TAYLOR ,  Jing WANG

IPC: A61K31/496 ,  A61K47/38 ,  A61K47/26 ,  A61K47/02 ,  A61K47/22 ,  A61K31/519 ,  A61P35/00

Abstract: The present application relates to treating and/or preventing breast cancer, including locally advanced or metastatic, ER+, HER2− breast cancer, in a subject in need of treatment, comprising administering a compound of Formula (I), or a pharmaceutically acceptable salt, enantiomer, stereoisomer, solvate, polymorph, isotopic derivative, or prodrug thereof, wherein R1, R2, R3, R4, m, and n are defined herein.

公开(公告)号：US20240299366A1

公开(公告)日：2024-09-12

申请号：US18456718

申请日：2023-08-28

Applicant: Arvinas Operations, Inc.

Inventor： Andrew P. CREW ,  Craig M. Crews ,  Hanqing Dong ,  Jing Wang ,  Yimin Qian ,  Meizhong Jin

IPC: A61K31/426 ,  A61K31/454 ,  A61K31/505 ,  A61K31/551 ,  A61K45/06 ,  A61K47/54 ,  A61K47/66 ,  C07D401/04 ,  C07D401/14 ,  C07D409/14 ,  C07D417/14 ,  C07D487/04 ,  C07D495/14 ,  C07D498/14 ,  C07K14/47 ,  C07K14/72 ,  C12N9/12 ,  C12N9/18 ,  C12Q1/25

CPC classification number: A61K31/426 ,  A61K31/454 ,  A61K31/505 ,  A61K31/551 ,  A61K45/06 ,  A61K47/545 ,  A61K47/555 ,  A61K47/66 ,  C07D401/04 ,  C07D401/14 ,  C07D409/14 ,  C07D417/14 ,  C07D487/04 ,  C07D495/14 ,  C07D498/14 ,  C07K14/4705 ,  C07K14/721 ,  C12N9/12 ,  C12N9/18 ,  C12Q1/25 ,  C12Y207/11001 ,  C12Y301/01031 ,  G01N2333/9015 ,  G01N2500/02

Abstract: The description relates to imide-based 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 invention. 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：US20240217962A1

公开(公告)日：2024-07-04

申请号：US18486668

申请日：2023-10-13

Applicant: Arvinas Operations, Inc.

Inventor： Andrew P. CREW ,  Michael BERLIN ,  Angela M. CACACE ,  Julian T. CHANDLER

IPC: C07D417/14 ,  A61K45/06 ,  A61K47/54 ,  C07D401/04 ,  C07D487/04

CPC classification number: C07D417/14 ,  A61K47/54 ,  C07D401/04 ,  C07D487/04 ,  A61K45/06

Abstract: The present disclosure relates to bifunctional compounds, which find utility as modulators of tau protein. In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a VHL or cereblon ligand which binds to the E3 ubiquitin ligase and on the other end a moiety which binds tau protein, such that tau protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of tau. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of tau protein. Diseases or disorders that result from aggregation or accumulation of tau protein are treated or prevented with compounds and compositions of the present disclosure.

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：US20220193072A1

公开(公告)日：2022-06-23

申请号：US17548842

申请日：2021-12-13

Applicant: Arvinas Operations, Inc.

Inventor： Xin CHEN ,  Andrew P. CREW ,  John FLANAGAN ,  Sheryl Maxine GOUGH ,  Royal J. HASKELL, III ,  Marcia Dougan MOORE ,  Yimin QIAN ,  Ian Charles Anthony TAYLOR ,  Jing WANG

IPC: A61K31/497 ,  A61P35/04 ,  A61K31/519

Abstract: The present application relates to treating and/or preventing breast cancer, including locally advanced or metastatic, ER+, HER2− breast cancer, in a subject in need of treatment, comprising administering a compound of Formula (I), or a pharmaceutically acceptable salt, enantiomer, stereoisomer, solvate, polymorph, isotopic derivative, or prodrug thereof, wherein R1, R2, R3, R4, m, and n are defined herein.