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.

公开(公告)号：US20240059686A1

公开(公告)日：2024-02-22

申请号：US18085500

申请日：2022-12-20

Applicant: Arvinas Operations, Inc.

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

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

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

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.