ERβ ligands. Part 4: Synthesis and structure–activity relationships of a series of 2-phenylquinoline derivatives

A new class of estrogen receptor β (ERβ) ligands based on the 2-phenylquinoline scaffold was prepared. Several analogues with C4 substitution displayed high affinity (3–5 nM) and significant selectivity (up to 83-fold) for ERβ. The best compound, 13b, was profiled as a selective partial agonist for ERβ at 1 μM in a cell-based transcriptional assay. Uterine weight bioassay of 13b indicated no activation of ERα in vivo.

Graphical abstractA series of 2-phenylquinoline derivatives was prepared and displayed high affinity and significant selectivity for estrogen receptor β.Figure optionsDownload full-size imageDownload as PowerPoint slide