Synthesis and evaluation of 17α-(carboranylalkyl)estradiols as ligands for estrogen receptors α and β

Abstract A series of 17α-(carboranylalkyl)estradiols was synthesized using cross-metathesis reaction of 17α-allyl- and 17α-vinylestradiols with allylcarboranes catalyzed by Hoveyda-Grubbs 2nd generation catalyst. The prepared estradiol derivatives were tested in the panel of cell-based reporter assays including all steroid receptors. The compounds mainly activated estrogen receptors α and β and tended to be weakly selective for ERα. Besides ERα and ERβ, we have also detected a weak agonistic activity on AR and PR at micromolar concentrations. We didn't observe any antagonistic effect with the exception of two receptors: GR and MR which were inhibited with some of the tested ligands. However, the inhibition was detectable at concentrations exceeding by far those needed to activate estrogen receptors.