公开(公告)号：US20240182464A1

公开(公告)日：2024-06-06

申请号：US18275379

申请日：2022-02-01

申请人： Les Laboratoirens Serviece ,  Novartis AG

发明人： András Herner ,  Piroska Markacz ,  Gang Liu ,  Katsumasa Nakajima ,  Tibor Novak ,  Georges-Alain Franzetti ,  Jérôme-Benoît Starck ,  Frédéric Colland ,  Patrice Desos ,  Attila Paczal ,  Bianka Szokol ,  Mátyás Pál Timari ,  Vilibald Kun ,  Matthew T. Burger ,  Joseph Anthony D'Alessio ,  Katherine Elizabeth Seiss ,  Rany Mathew Thomas ,  Liang Zhao

IPC分类号： C07D471/04 ,  A61P35/00 ,  C07D417/14

CPC分类号： C07D471/04 ,  A61P35/00 ,  C07D417/14

摘要： The present disclosure provides PROTAC compounds represented by Formula (A): D-L-DSM (A), or an enantiomer, a diastereoisomer, and/or a pharmaceutically acceptable salt of any one of the foregoing, wherein: DSM is a degradation signaling compound {e.g., an E3 ubiquitin ligase recruitment ligand, such as a CRBN ligand or a VHL ligand) covalently attached to a linker L; L is a linker that covalently attaches DSM to D; and D is a Bcl-xL inhibitor compound of Formula (I) or Formula (II) covalently attached to the linker L: (I); (II) wherein the definitions for the variables are described herein. Also provided are pharmaceutical compositions comprising the PROTAC compounds of the present disclosure and methods of use and methods of making thereof.