Synthesis and evaluation of 17α-(dimethylphenyl)vinyl estradiols as probes of the estrogen receptor-α ligand binding domain

► Efficient synthesis of novel probes of estrogen receptor ligand binding domain/pocket. ► Competitive binding results demonstrate high affinity for ortho (2-) substituted derivatives. ► Good correlation between binding affinity and agonist potency in ER-responsive cells. ► Molecular modeling studies show binding potential binding mode in ER-LBP.