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https://hdl.handle.net/2440/75407
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Type: | Journal article |
Title: | Elemental isomerism: a boron-nitrogen surrogate for a carbon-carbon double bond increases the chemical diversity of estrogen receptor ligands |
Author: | Zhou, H. Nettles, K. Bruning, J. Kim, Y. Joachimiak, A. Sharma, S. Carlson, K. Stossi, F. Katzenellenbogen, B. Greene, G. Katzenellenbogen, J. |
Citation: | Chemistry and Biology, 2007; 14(6):659-669 |
Publisher: | Cell Press |
Issue Date: | 2007 |
ISSN: | 1074-5521 1879-1301 |
Statement of Responsibility: | Hai-Bing Zhou, Kendall W. Nettles, John B. Bruning, Younchang Kim, Andrzej Joachimiak, Sanjay Sharma, Kathryn E. Carlson, Fabio Stossi, Benita S. Katzenellenbogen, Geoffrey L. Greene, and John A. Katzenellenbogen |
Abstract: | To 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. |
Keywords: | CHEMBIOL |
Rights: | Copyright © 2007 Elsevier Ltd. All rights reserved. |
DOI: | 10.1016/j.chembiol.2007.04.009 |
Published version: | http://dx.doi.org/10.1016/j.chembiol.2007.04.009 |
Appears in Collections: | Aurora harvest 4 Molecular and Biomedical Science publications |
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