公开(公告)号：US11827636B2

公开(公告)日：2023-11-28

申请号：US17561032

申请日：2021-12-23

申请人： DANA-FARBER CANCER INSTITUTE, INC.

发明人： Nathanael S. Gray ,  Tinghu Zhang ,  Calla M. Olson ,  Yanke Liang ,  Nicholas Kwiatkowski

IPC分类号： C07D471/04 ,  C07D471/10 ,  A61K47/18 ,  A61K47/54 ,  A61P35/00

CPC分类号： C07D471/04 ,  A61K47/18 ,  A61K47/545 ,  C07D471/10 ,  A61P35/00

摘要： The present application provides bifunctional compounds of Formula (Ia) or (Ib):




or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, which act as protein degradation inducing moieties for cyclin-dependent kinase 8 (CDK8). The present application also relates to methods for the targeted degradation of CDK8 through the use of the bifunctional compounds that link a ubiquitin ligase-binding moiety to a ligand that is capable of binding to CDK8 which can be utilized in the treatment of disorders modulated by CDK8.

公开(公告)号：US20220112191A1

公开(公告)日：2022-04-14

申请号：US17561032

申请日：2021-12-23

申请人： DANA-FARBER CANCER INSTITUTE, INC.

发明人： Nathanael S. Gray ,  Tinghu Zhang ,  Calla M. Olson ,  Yanke Liang ,  Nicholas Kwiatkowski

IPC分类号： C07D471/04 ,  A61K47/54 ,  A61K47/18 ,  C07D471/10 ,  A61P35/00

摘要： The present application provides bifunctional compounds of Formula (Ia) or (Ib): or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, which act as protein degradation inducing moieties for cyclin-dependent kinase 8 (CDK8). The present application also relates to methods for the targeted degradation of CDK8 through the use of the bifunctional compounds that link a ubiquitin ligase-binding moiety to a ligand that is capable of binding to CDK8 which can be utilized in the treatment of disorders modulated by CDK8.

公开(公告)号：US11247991B2

公开(公告)日：2022-02-15

申请号：US17083940

申请日：2020-10-29

申请人： DANA-FARBER CANCER INSTITUTE, INC.

发明人： Nathanael S. Gray ,  Tinghu Zhang ,  Calla M. Olson ,  Yanke Liang ,  Nicholas Kwiatkowski

IPC分类号： C07D471/04 ,  C07D471/10 ,  C07D401/14 ,  A61K47/54 ,  A61K47/18 ,  A61P35/00

摘要： The present application provides bifunctional compounds of Formula (Ia) or (Ib): or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, which act as protein degradation inducing moieties for cyclin-dependent kinase 8 (CDK8). The present application also relates to methods for the targeted degradation of CDK8 through the use of the bifunctional compounds that link a ubiquitin ligase-binding moiety to a ligand that is capable of binding to CDK8 which can be utilized in the treatment of disorders modulated by CDK8.

公开(公告)号：US10532103B2

公开(公告)日：2020-01-14

申请号：US16094102

申请日：2017-04-21

申请人： Dana-Farber Cancer Institute, Inc.

发明人： Nathanael S. Gray ,  Tinghu Zhang ,  Calla M. Olson ,  Yanke Liang ,  Nicholas Kwiatkowski

IPC分类号： A61K47/55 ,  A61K31/427 ,  A61K31/4523 ,  C07D417/14

摘要： The present application provides bifunctional compounds of Formula (I): or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof, which act as protein degradation inducing moieties for cyclin-dependent kinase 9 (CDK9), the present application also relates to methods for the targeted degradation of CDK9 through the use of the bifunctional compounds that link a ubiquitin ligase-binding moiety to a ligand that is capable of binding to CDK9 which can be utilized in the treatment of disorders modulated by CDK9.