公开(公告)号：US20180177750A1

公开(公告)日：2018-06-28

申请号：US15851053

申请日：2017-12-21

申请人： Arvinas, Inc.

发明人： Andrew P. Crew ,  Lawrence B. Snyder ,  Jing Wang ,  Hanqing Dong ,  Yimin Qian ,  Michael Berlin

IPC分类号： A61K31/166 ,  A61K31/405 ,  A61K47/54 ,  A61K31/351 ,  A61K38/45 ,  C12N9/10 ,  A61P35/00

CPC分类号： A61K31/166 ,  A61K31/351 ,  A61K31/405 ,  A61K38/45 ,  A61K47/545 ,  A61K47/55 ,  A61K47/555 ,  A61P35/00 ,  C07D401/14 ,  C07D405/12 ,  C07D405/14 ,  C07D409/14 ,  C07D417/14 ,  C07D471/04 ,  C12N9/1007 ,  C12Y201/01043

摘要： The present disclosure relates to bifunctional compounds, which find utility as modulators of enhancer of zeste homolog 2 (target protein). 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：US20180125821A1

公开(公告)日：2018-05-10

申请号：US15801243

申请日：2017-11-01

申请人： Arvinas, Inc.

发明人： Andrew P. Crew ,  Michael Berlin ,  John J. Flanagan ,  Hanqing Dong ,  Alexey Ishchenko

IPC分类号： A61K31/4166 ,  A61K31/495 ,  A61K31/381 ,  C07D401/14 ,  C07D417/14 ,  C07D401/04

摘要： 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：US20170037004A1

公开(公告)日：2017-02-09

申请号：US15209648

申请日：2016-07-13

申请人： Arvinas, Inc.

发明人： Andrew P. Crew ,  Michael Berlin ,  Hanqing Dong ,  Yimin Qian

IPC分类号： C07D207/16 ,  C07D417/14 ,  A61K31/496 ,  C07D471/04 ,  A61K31/444 ,  A61K45/06 ,  A61K31/506 ,  C07D487/14 ,  A61K31/551 ,  C07D519/00 ,  C07D403/12 ,  A61K31/4178 ,  A61K31/40 ,  A61K31/4439

CPC分类号： C07D207/16 ,  A61K31/40 ,  A61K31/4178 ,  A61K31/4439 ,  A61K31/444 ,  A61K31/496 ,  A61K31/506 ,  A61K31/551 ,  A61K38/00 ,  A61K45/06 ,  A61K47/55 ,  C07D401/04 ,  C07D403/04 ,  C07D403/12 ,  C07D405/14 ,  C07D417/04 ,  C07D417/14 ,  C07D471/04 ,  C07D487/14 ,  C07D495/14 ,  C07D519/00 ,  C07K2319/00

摘要： The description relates to Inhibitors of Apoptosis Proteins (IAPs) 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 invention. In particular, the description provides compounds, which contain on one end a ligand which binds to the IAP 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.

摘要翻译： 该描述涉及凋亡蛋白（IAP）结合化合物的抑制剂，包括其中包含其的双官能化合物，其可用作靶向泛素化的调节剂，特别是多种多肽和其他蛋白质的抑制剂，其被降解和/或以其它方式被双功能抑制 根据本发明的化合物。 特别地，该描述提供化合物，其一端含有与IAP E3泛素连接酶结合的配体，另一端含有结合靶蛋白的部分，使得靶蛋白置于接近泛素连接酶的作用下 降解（和抑制）该蛋白质。 可以合成化合物，其表现出与几乎任何类型的靶向多肽的降解/抑制一致的广泛的药理活性。

公开(公告)号：US20170008904A1

公开(公告)日：2017-01-12

申请号：US15206497

申请日：2016-07-11

申请人： Arvinas, Inc.

发明人： Andrew P. Crew ,  Craig M. Crews ,  Hanqing Dong ,  Yimin Qian ,  Jing Wang

IPC分类号： C07D495/14 ,  C07D417/12 ,  C07D401/14 ,  C07D207/16 ,  C07D401/12 ,  C07D405/14 ,  A61K47/48 ,  A61K31/551 ,  A61K31/40 ,  A61K31/427 ,  A61K31/4166 ,  A61K31/496 ,  A61K31/166 ,  A61K31/4433 ,  A61K31/506 ,  A61K45/06

CPC分类号： C07D495/14 ,  A61K31/337 ,  A61K31/4184 ,  A61K31/436 ,  A61K31/4545 ,  A61K31/4995 ,  A61K31/506 ,  A61K31/593 ,  A61K31/664 ,  A61K31/704 ,  A61K45/06 ,  A61K47/55 ,  C07D207/16 ,  C07D401/12 ,  C07D401/14 ,  C07D405/14 ,  C07D417/12 ,  A61K2300/00

摘要： The description relates to MDM2 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 invention. In particular, the description provides compounds, which contain on one end a ligand which binds to the MDM2 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.

摘要翻译： 所述描述涉及MDM2结合化合物，包括其包含其的双功能化合物，其可用作靶向泛素化的调节剂，特别是多种多肽的抑制剂和根据本发明的双功能化合物降解和/或以其它方式抑制的其它蛋白质 。 特别地，该描述提供化合物，其在一端含有与MDM2 E3泛素连接酶结合的配体，另一端包含结合靶蛋白的部分，使得靶蛋白置于接近泛素连接酶的作用下 降解（和抑制）该蛋白质。 可以合成化合物，其表现出与几乎任何类型的靶向多肽的降解/抑制一致的广泛的药理活性。

公开(公告)号：US20160045607A1

公开(公告)日：2016-02-18

申请号：US14822309

申请日：2015-08-10

申请人： Yale University ,  Arvinas, Inc.

发明人： Andrew Crew ,  Craig Crews ,  Hanqing Dong ,  Eunhwa Ko ,  Jing Wang

IPC分类号： A61K47/48 ,  A61K31/426 ,  A61K31/427 ,  A61K45/06

CPC分类号： A61K47/481 ,  A61K31/426 ,  A61K31/427 ,  A61K38/00 ,  A61K45/06 ,  A61K47/545 ,  A61K47/55 ,  C07K5/06026 ,  C07K5/06034 ,  C07K5/06052 ,  C07K5/0821

摘要： The present invention relates to bifunctional compounds, 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 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 a target protein such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of that protein. The present invention exhibits a broad range of pharmacological activities associated with compounds according to the present invention, consistent with the degradation/inhibition of targeted polypeptides.

摘要翻译： 本发明涉及双官能化合物，其可用作靶向泛素化的调节剂，特别是根据本发明的双官能化合物降解和/或以其它方式抑制的多种多肽和其它蛋白质的抑制剂。 特别地，本发明涉及化合物，其一端含有与泛素连接酶结合的VHL配体，另一端含有结合靶蛋白的部分，使得靶蛋白置于接近泛素连接酶 以实现该蛋白质的降解（和抑制）。 与靶向多肽的降解/抑制一致，本发明表现出与根据本发明的化合物相关的广泛的药理学活性。