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：US20240409529A1

公开(公告)日：2024-12-12

申请号：US18747080

申请日：2024-06-18

Applicant: Arvinas Operations, Inc

Inventor： Laura E.N. ALLAN ,  Chungpin Herman CHEN ,  Hanqing DONG ,  Robert J. DUGUID ,  John A. GROSSO ,  Royal J. HASKELL, III ,  Casey Keith JAGER ,  Venkata A. KATTUBOINA ,  Aditya Mohan KAUSHAL ,  Samuel Elliott KENNEDY ,  Rhys LLOYD ,  Miranda Annell NEESER ,  Yuping QIU ,  Hayley REECE ,  Maxwell Marco REEVE ,  Joseph P. REO ,  Jerod ROBERTSON ,  Mohammad Mehdi ZAHEDI

IPC: C07D401/14 ,  A61K9/00 ,  A61K9/20 ,  A61K45/06

Abstract: The present disclosure relates to ultra-pure forms, polymorphs, amorphous forms, and formulations of N-[(1r,4r)-4-(3-chloro-4-cyanophenoxy)cyclohexyl]-6-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxo-2,3-dihydro-1H-isoindol-5-yl]piperazin-1-yl}methyl)piperidin-1-yl]pyridazine-3-carboxamide, referred to herein as Compound A: The present disclosure also relates methods of manufacturing and purifying the same, as well as intermediates useful in the synthesis of Compound A. The ultra-pure forms, polymorphs, amorphous forms, and formulations of Compound A can be used as therapeutic agents for the treatment of various diseases and conditions such as cancer.

公开(公告)号：US20230082997A1

公开(公告)日：2023-03-16

申请号：US17571018

申请日：2022-01-07

Applicant: Arvinas Operations, Inc.

Inventor： Michael BERLIN ,  Andrew P. CREW ,  Craig M. CREWS ,  Hanqing DONG ,  Keith R. HORNBERGER ,  Yimin QIAN ,  Lawrence B. SNYDER ,  Jing WANG ,  Kurt ZIMMERMANN

IPC: A61K47/55 ,  C07D401/04 ,  C07D401/14 ,  C07D471/04 ,  A61K31/437 ,  A61K31/497 ,  A61K31/551 ,  A61K45/06 ,  A61K31/501 ,  A61K31/506 ,  A61K31/496 ,  A61K47/54 ,  A61P35/00

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：US20230012321A1

公开(公告)日：2023-01-12

申请号：US17313679

申请日：2021-05-06

Applicant: Arvinas Operations, Inc.

Inventor： Laura E.N. ALLAN ,  Chungpin Herman CHEN ,  Hanqing DONG ,  Robert J. DUGUID ,  John A. GROSSO ,  Royal J. HASKELL, III ,  Casey Keith JAGER ,  Venkata A. KATTUBOINA ,  Aditya Mohan KAUSHAL ,  Samuel Elliott KENNEDY ,  Rhys LLOYD ,  Miranda Annell NEESER ,  Yuping QIU ,  Hayley REECE ,  Maxwell Marco REEVE ,  Joseph P. REO ,  Jerod ROBERTSON ,  Mohammad Mehdi ZAHEDI

IPC: C07D401/14 ,  A61K9/00 ,  A61K9/20 ,  A61K45/06

Abstract: The present disclosure relates to ultra-pure forms, polymorphs, amorphous forms, and formulations of N-[(1r,4r)-4-(3-chloro-4-cyanophenoxy)cyclohexyl]-6-[4-({4-[2-(2,6-dioxopiperidin-3-yl)-6-fluoro-1,3-dioxo-2,3-dihydro-1H-isoindol-5-yl]piperazin-1-yl}methyl)piperidin-1-yl]pyridazine-3-carboxamide, referred to herein as Compound A: The present disclosure also relates methods of manufacturing and purifying the same, as well as intermediates useful in the synthesis of Compound A. The ultra-pure forms, polymorphs, amorphous forms, and formulations of Compound A can be used as therapeutic agents for the treatment of various diseases and conditions such as cancer.

公开(公告)号：US20220089570A1

公开(公告)日：2022-03-24

申请号：US17484628

申请日：2021-09-24

Applicant: Arvinas Operations, Inc.

Inventor： Andrew P. CREW ,  Craig M. CREWS ,  Hanqing DONG ,  Meizhong JIN ,  Yimin QIAN ,  Jing WANG

IPC: C07D401/14 ,  C12N9/12 ,  C12N9/18 ,  A61K45/06 ,  C12Q1/25 ,  A61K31/4439 ,  A61K31/519 ,  A61K31/513 ,  A61K47/54 ,  A61K47/66

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.