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

•Cross-metathesis reaction between 17α-vinyl- and 17α-allylestradiols with allylcarboranes was studied.•Two types of 17α-substituted estradiols bearing various carborane cages were synthesized.•The compounds were tested in cell-based reporter assays.•The compounds mainly activated estrogen receptors α and β and tended to be weakly selective for ERα.

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.

Graphical abstractCross metathesis offers a convenient approach for synthesis of a series of 17α-(carboranylalkyl)estradiols that tested as ligands for estrogen receptors.Figure optionsDownload full-size imageDownload as PowerPoint slide