Compounds and methods for the targeted degradation of androgen receptor
The present disclosure relates to bifunctional compounds, which find utility to degrade and (inhibit) Androgen Receptor. In particular, the present disclosure is directed to compounds, which contain on one end a cereblon ligand which binds to the E3 ubiquitin ligase and on the other end a moiety which binds Androgen Receptor, such that Androgen Receptor is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of Androgen Receptor. The present disclosure exhibits a broad range of pharmacological activities associated with compounds according to the present disclosure, consistent with the degradation/inhibition of Androgen Receptor.
1. A compound selected from the group consisting of:
or a pharmaceutically acceptable salt, enantiomer, stereoisomer, solvate, polymorph, isotopic derivative, or prodrug thereof.
2. A compound having the structure
or a pharmaceutically acceptable salt, enantiomer, stereoisomer, solvate or polymorph thereof.
3. A compound having the structure
or a pharmaceutically acceptable salt, enantiomer, stereoisomer, solvate or polymorph thereof.
4. A compound having the structure:
or a pharmaceutically acceptable salt, enantiomer, stereoisomer, solvate or polymorph thereof.
5. A compound having the structure
or a pharmaceutically acceptable salt, enantiomer, stereoisomer, solvate or polymorph thereof.
6. A pharmaceutical composition comprising a compound of claim 1 , and a pharmaceutically acceptable carrier.