Bibenzyl- and stilbene-core compounds with non-polar linker atom substituents as selective ligands for estrogen receptor beta

A series of structurally simple bibenzyl-diol and stilbene-diol core molecules, structural analogs of the well-known hexestrol and diethylstilbestrol non-steroidal estrogens, were prepared and evaluated as estrogen receptor (ER) subtype-selective ligands. Analysis of their ER alpha and ER beta binding showed that certain substitution patterns engendered binding affinities that were >100-fold selective for ER beta. When further investigated in cell-based gene transcription assays, some molecules showed similarly high relative transcriptional potency selectivity in favor of ER beta. Interestingly, the most ER beta-selective molecules were those bearing non-polar substituents on one of the internal carbon atoms. These compounds should be useful probes for determining the physiological roles of ER beta, and they might lead to the development of more selective and thus safer pharmaceuticals. (C) 2009 Elsevier Masson SAS. All rights reserved.