Derivatives of 4-styrylpyridines: synthesis, estrogen receptor binding affinity, and photophysical properties

In order to develop novel ligands for the estrogen receptor (ER) that might have high binding affinity and fluorescence properties suitable for assaying ER levels in cells, we have prepared a series of substituted 4'-hydroxyl-styrylpyridines and phenylethylpyridines and studied their optical spectroscopy and receptor binding properties. Several derivatives that contain alkyl substituents on the internal ethene or ethane carbons were prepared. While most of these compounds have only modest affinity for ER, one fluorescent analog, (E)-1-(4-hydroxyphenyl)-1-phenyl-2-(4-pyridinyl)ethene(13), has reasonably good binding affinity for ER and shows long wavelength fluorescence emission that is sensitive to solvent polarity and pH. This compound may prove to be a useful probe for detecting ER in cells.