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

A new class of estrogen receptor beta (ERbeta) 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 ERbeta. The best compound, 13b, was profiled as a selective partial agonist for ERbeta at 1 muM in a cell-based transcriptional assay. Uterine weight bioassay of 13b indicated no activation of ERalpha in vivo.