COMPOUNDS FOR TARGETING DEGRADATION OF BRUTON'S TYROSINE KINASE

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...

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Bibliographische Detailangaben
Hauptverfasser: Yap, Jeremy L, Anderson, Corey Don, Hopkins, Brian T, Ahn, Jae Young, Stefan, Eric, Cheng, Xinpeng, Marx, Isaac, Nevalainen, Marta, O'Shea, Morgan Welzel, Guckian, Kevin M
Format: Patent
Sprache:eng
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Zusammenfassung: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.