Constrained phytoestrogens and analogues as ERβ selective ligands

A new series of ERbeta (ERβ) selective ligands has been prepared. One of the compounds 6, structurally related to the phytoestrogen apigenin 4, displays a binding preference for ERβ over ERα of over 40-fold. In addition to its binding selectivity, 6 was able to potently induce metallothionein (an ERβ specific response in human SAOS-2 cells) while demonstrating low potency in an ERα dependant ERE-tk luciferase assay in MCF-7 cells. Such receptor and cell selectivity could make 6 a useful molecular probe for better understanding the role of ERβ in mammalian physiology.