Zhou, H.Nettles, K.Bruning, J.Kim, Y.Joachimiak, A.Sharma, S.Carlson, K.Stossi, F.Katzenellenbogen, B.Greene, G.Katzenellenbogen, J.2013-02-122013-02-122007Chemistry and Biology, 2007; 14(6):659-6691074-55211879-1301http://hdl.handle.net/2440/75407To increase the chemical diversity of bioactive molecules by incorporating unusual elements, we have examined the replacement of a C=C double bond with the isoelectronic, isostructural B-N bond in the context of nonsteroidal estrogen receptor (ER) ligands. While the B-N bond was hydrolytically labile in the unhindered cyclofenil system, the more hindered anilino dimesitylboranes, analogs of triarylethylene estrogens, were easily prepared, hydrolytically stable, and demonstrated substantial affinity for ERs. X-ray analysis of one ERalpha-ligand complex revealed steric clashes with the para methyl groups distorting the receptor; removal of these groups resulted in an increase in affinity, potency, and transcriptional efficacy. These studies define the structural determinants of stability and cellular bioactivity of a B-N for C=C substitution in nonsteroidal estrogens and provide a framework for further exploration of "elemental isomerism" for diversification of drug-like molecules.enCopyright © 2007 Elsevier Ltd. All rights reserved.CHEMBIOLJournal article002012132810.1016/j.chembiol.2007.04.0090002476725000082-s2.0-3425036110623521Bruning, J. [0000-0002-6919-1824]