Synthesis and evaluation of aryl-substituted diarylpropionitriles, selective ligands for estrogen receptor beta, as positron-emission tomographic imaging agents.

Article Details

Citation
Copy to clipboard

Moon BS, Carlson KE, Katzenellenbogen JA, Choi TH, Chi DY, Kim JY, Cheon GJ, Koh HY, Lee KC, An G

Synthesis and evaluation of aryl-substituted diarylpropionitriles, selective ligands for estrogen receptor beta, as positron-emission tomographic imaging agents.

Bioorg Med Chem. 2009 May 1;17(9):3479-88. doi: 10.1016/j.bmc.2009.02.064. Epub 2009 Mar 9.

PubMed ID
19359182 [ View in PubMed
]
Abstract

We have investigated halogen-substituted non-steroidal estrogens with selective binding affinity for the estrogen receptor beta (ERbeta that might be used for imaging the levels of this ER-subtype in breast tumors by positron emission tomography (PET). Based on diarylpropionitrile (DPN, 1a), a compound previously reported that has a 72-fold binding selectivity for ERbeta, we developed a series of DPN analogs having methyl-, hydroxyl-, and halogen substituents, including fluoroethyl and fluoropropyl groups. In competitive radiometric binding assays with [(3)H]estradiol, all of these DPN analogs showed high ERbeta/ERalpha selectivity; while the selectivity varied, in some cases it reached nearly 300-fold (RBA: ERalpha, 0.023%; ERbeta, 6.25%). The absolute ERbeta binding affinities, however, were not sufficient to merit further consideration for developing these ligands as PET imaging agents.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
EstradiolEstrogen receptor alphaKd (nM)0.2N/AN/ADetails
EstradiolEstrogen receptor betaKd (nM)0.5N/AN/ADetails