公开(公告)号：US20240343733A1

公开(公告)日：2024-10-17

申请号：US18576940

申请日：2022-07-07

申请人： BIOGEN MA INC. ,  C4 THRAPEUTICS, INC.

发明人： Kevin M. Guckian ,  Emily Anne Peterson ,  Fang Gao ,  Ryan Evans ,  Eric Stefan ,  Jeremy L. Yap ,  Corey Don Anderson ,  Morgan Welzel O'Shea ,  Jae Young M. Ahn ,  Christopher G. Nasveschuk ,  James A. Henderson

IPC分类号： C07D487/04 ,  A61K31/4545 ,  A61K31/513 ,  A61K31/519 ,  C07D401/14 ,  C07D471/04 ,  C07D487/10 ,  C07D519/00

CPC分类号： C07D487/04 ,  A61K31/4545 ,  A61K31/513 ,  A61K31/519 ,  C07D401/14 ,  C07D471/04 ,  C07D487/10 ,  C07D519/00

摘要： This disclosure relates to compounds of Formula (A): IRAK-L-DSM (A), or a pharmaceutically acceptable salt thereof, wherein DSM is a degradation signaling moiety that is covalently attached to the linker L, L is a linker that covalently attaches IRAK to DSM; and IRAK is an IRAK4 binding moiety represented by Formula (I) that is covalently attached to linker L; in which all of the variables are as defined in the application. Compounds or pharmaceutically acceptable salts thereof as described herein are capable of activating the selective ubiqitination of IRAK4 proteins via the ubiquitin-proteasome pathways (UPP) and cause degradation of IRAK4 proteins. The present disclosure also provides methods of treating disorders responsive to modulation of IRAK4 activity and/or degradation of IRAK4 with at least one compound described herein.

公开(公告)号：US20240287076A1

公开(公告)日：2024-08-29

申请号：US18289438

申请日：2022-05-05

申请人： BIOGEN MA INC. ,  C4 THERAPEUTICS, INC.

发明人： Kevin M. Guckian ,  Eric Stefan ,  Corey Don Anderson ,  Jae Young Ahn ,  Morgan Welzel O'Shea ,  Jeremy L. Yap ,  Xinpeng Cheng ,  Brian T. Hopkins ,  Isaac Marx ,  Marta Nevalainen

IPC分类号： C07D487/04 ,  A61K31/53

CPC分类号： C07D487/04 ,  A61K31/53

摘要： This disclosure relates to compounds of Formula (A): BTK-L-DSM (A) or a pharmaceutically acceptable salt thereof, wherein DSM is a degradation signaling moiety that is covalently attached to the linker L, L is a linker that covalently attaches BTK to DSM, and BTK is a Btk binding moiety represented by Formula (I) or Formula (II) that is covalently attached to linker L: in which all of the variables are as defined in the application. Compounds or pharmaceutically acceptable salts thereof as described herein are capable of activating the selective ubiqitination of Btk proteins via the ubiquitin-proteasome pathways (UPP) and cause degradation of Btk proteins. The present disclosure also provides methods of treating disorders responsive to modulation of Btk activity and/or degradation of Btk with at least one compound described herein.