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Synlett
DOI: 10.1055/s-0043-1775444
DOI: 10.1055/s-0043-1775444
letter
Small Molecules in Medicinal Chemistry
Analogues of the Potent and Selective ERβ Agonist trans-4-(4-Hydroxyphenyl)cyclohexanemethanol: Synthesis and Evaluation
This work was supported by the National Institutes of General Medical Sciences (grant R15GM118304).
This manuscript is dedicated to Prof. Russell P. Hughes for his lifetime contributions to organofluorine chemistry.
Abstract
Activation of estrogen receptor-beta (ERβ) has potential benefits for vasomotor symptoms as well as memory consolidation in menopausal women. Ten 4-(4-substituted cyclohexyl)phenols were synthesized and evaluated as ERβ agonists in a TR-FRET ligand displacement assay. Four of the more potent compounds, all of which contained fluoroalkyl groups as the 4-substituent, were further assessed for agonist and antagonist activity in cell-based functional assays for ERβ and ERα. The 4-(4-fluoroalkyl-cyclohexyl)phenols were all >50-fold selective for ERβ over ERα, and none were found to be antagonists for either ERβ or ERα at 7,250 nM. Detection of 200 μM of trans-4-(4-(fluoromethyl)cyclohexyl)phenol in the presence of mouse brain homogenate was possible by 19F NMR spectroscopy.
Supporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/s-0043-1775444.
- Supporting Information
Publication History
Received: 04 December 2024
Accepted after revision: 16 January 2025
Article published online:
21 February 2025
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