SELECTIVE BCL-XL PROTAC COMPOUNDS AND METHODS OF USE

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, suc...

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Hauptverfasser: FRANZETTI, Georges-Alain, COLLAND, Frederic, NOVAK, Tibor, ZHAO, Liang, NAKAJIMA, Katsumasa, TIMARI, Mátyás, Pál, D'ALESSIO, Joseph, Anthony, SEISS, Katherine, Elizabeth, HERNER, András, THOMAS, Ranny, Matthew, SZOKOL, Bianka, KUN, Vilibald, DESOS, Patrice, MARKACZ, Piroska, STARCK, Jérôme-Benoît, PACZAL, Attila, LIU, Gang, BURGER, Matthew, T
Format: Patent
Sprache:eng ; fre ; ger
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Zusammenfassung: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.