Synthesis of 3-alkyl naphthalenes as novel estrogen receptor ligands

A novel series of 3-alkyl naphthalenes and their activity against estrogen receptor are reported. A series of estrogen receptor ligands based on a 3-alkyl naphthalene scaffold was synthesized using an intramolecular enolate-alkyne cycloaromatization as the key step. Several of these compounds bearing a C6-OH group were shown to be high affinity ligands. All compounds had similar ERα and ERβ binding affinity ranging from micromolar to low nanomolar.