Vu An T, Cohn Stephen T, Manas Eric S, Harris Heather A, Mewshaw Richard E
Chemical and Screening Sciences, Wyeth Research, 500 Arcola Road, Collegeville, PA 19426, USA.
Bioorg Med Chem Lett. 2005 Oct 15;15(20):4520-5. doi: 10.1016/j.bmcl.2005.07.008.
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.
制备了一类基于2-苯基喹啉骨架的新型雌激素受体β（ERβ）配体。几种具有C4取代的类似物对ERβ显示出高亲和力（3-5 nM）和显著的选择性（高达83倍）。在基于细胞的转录分析中，最佳化合物13b在1 μM时被表征为ERβ的选择性部分激动剂。13b的子宫重量生物测定表明其在体内未激活ERα。
