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

초록

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