Modulators of BTK proteolysis and methods of use

A compound, or a pharmaceutically acceptable salt, enantiomer, stereoisomer, solvate, polymorph, or prodrug thereof, having the structure:

• ULM-L-PTM,
• wherein:
• the ULM is an E3 ubiquitin ligase binding moiety that binds an E3 ubiquitin ligase;
• the PTM is a Bruton's Tyrosine Kinase (BTK) targeting moiety having the structure:
• wherein:
• at each occurrence XPTM is independently N or optionally substituted CH;
• RPTM1 is independently NRPTMP9PTM10, H, optionally substituted C3-C6 cycloalkyl,
• optionally substituted C3-C6 heteroalkyl, optionally substituted aryl, optionally substituted heteroaryl,
• RPTM9 and RPTM10 are each independently H, —(C═O)—RPTM9′, or optionally substituted C1-C6 alkyl;
• RPTM9′ is optionally substituted linear or branched alkyl, or optionally substituted alkene;
• at each occurrence RPTM2 is independently H, —O—RPTM3, optionally substituted linear or branched alkyl;
• at each occurrence RPTM3 is independently an optionally substituted aryl or optionally substituted heteroaryl;
• and
• the indicates a site of attachment of at least one of a linker, ULM, ULM′ or a combination thereof;
• and
• the L is a bond or a linker connecting the ULM and the PTM.