Synthesis and Evaluation of Estrogen Receptor ￥a-Selective Ligands: Fluoroalkylated Indazole Estrogens

摘要

It is important to identify selective ligands for the estrogen receptor subtypes ERメ or ERモ to evaluate them as pharmaceutical targets in breast cancer. To develop ERモ-selective ligands as PET imaging agents, a series of aryl indazole estrogen analogues substituted at the C3 position with fluoroethyl and fluoropropyl groups were synthesized and evaluated for their relative binding affinities and selectivities for ERメ vs ERモ. The fluoroethylated indazole estrogen (FEIE, 1i) and fluoropropylated indazole estrogen (FPIE, 1h) showed 41- fold and 17-fold ERモ/ERメ selectivity, respectively. However, their binding affinities to ERメ and ERモ were very low.