Tetrahydronaphthalene and tetrahydroisoquinoline derivatives as estrogen receptor degraders
The present disclosure relates to bifunctional compounds, which find utility as modulators of estrogen receptor (target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end at least one of a Von Hippel-Lindau ligand, a cereblon ligand, Inhibitors of Apoptosis Proteins ligand, mouse double-minute homolog 2 ligand, or a combination thereof, which binds to the respective E3 ubiquitin ligase, and on the other end a moiety which binds the target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aggregation or accumulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.
1. A compound having the structure:
or a pharmaceutically acceptable salt, enantiomer, stereoisomer, isotopic derivative, or prodrug of any of the foregoing.
2. A compound having the structure:
or a pharmaceutically acceptable salt, enantiomer, or stereoisomer thereof.
3. A compound having the structure:
or a pharmaceutically acceptable salt, enantiomer, or stereoisomer thereof.
4. A compound having the structure:
or a pharmaceutically acceptable salt, enantiomer, or stereoisomer thereof.
5. A compound having the structure:
or a pharmaceutically acceptable salt, enantiomer, or stereoisomer thereof.
6. A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier.