公开(公告)号：US20200038513A1

公开(公告)日：2020-02-06

申请号：US16523219

申请日：2019-07-26

申请人： ARVINAS OPERATIONS, INC. ,  YALE UNIVERSITY

发明人： Craig M. Crews ,  Philipp M. Cromm ,  Andrew P. Crew

IPC分类号： A61K47/54 ,  A61K45/06 ,  A61K31/505 ,  A61K31/427 ,  A61K31/454

摘要： The present disclosure relates to bifunctional compounds, which find utility as modulators of focal adhesion kinase (FAK) or protein tyrosine kinase 2 (PTK2). 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, 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：US11220515B2

公开(公告)日：2022-01-11

申请号：US16258563

申请日：2019-01-26

申请人： YALE UNIVERSITY

发明人： Craig M. Crews ,  George Burslem ,  Philipp M. Cromm ,  Saul Jaime-Figueroa ,  Momar Toure

IPC分类号： C07D495/14 ,  C07D261/08 ,  A61P35/00 ,  C07D417/14 ,  C07D413/14

摘要： 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：US11834460B2

公开(公告)日：2023-12-05

申请号：US17554831

申请日：2021-12-17

申请人： YALE UNIVERSITY

发明人： Craig M. Crews ,  George Burslem ,  Philipp M. Cromm ,  Saul Jaime-Figueroa ,  Momar Toure

IPC分类号： C07D495/14 ,  C07D261/08 ,  C07D413/14 ,  C07D417/14 ,  A61P35/00

CPC分类号： C07D495/14 ,  A61P35/00 ,  C07D261/08

摘要： 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.