Kim Seongkon, Wu Jane Y, Birzin Elizabeth T, Frisch Katalin, Chan Wanda, Pai Lee-Yuh, Yang Yi Tien, Mosley Ralph T, Fitzgerald Paula M D, Sharma Nandini, Dahllund Johanna, Thorsell Ann-Gerd, DiNinno Frank, Rohrer Susan P, Schaeffer James M, Hammond Milton L
Department of Medicinal Chemistry, Atherosclerosis and Endocrinology, Merck Research Laboratories, P.O. Box 2000, 800-B109 Rahway, New Jersey 07065, USA.
J Med Chem. 2004 Apr 22;47(9):2171-5. doi: 10.1021/jm034243o.
The discovery and synthesis of dihydrobenzoxathiins as potent, ERalpha subtype selective ligands are described. The most active analogue, 4-D, was found to be 50-fold selective in a competitive binding assay and 100-fold selective in a transactivation assay in HEK-293 cells. The alpha selectivity was postulated to lie in the interaction of the sulfur atom of the benzoxathiin ring with the two discriminating residues in the binding pocket of the receptor isoforms.
本文描述了二氢苯并[d] [1,3]噻嗪作为强效、雌激素受体α亚型选择性配体的发现与合成。在竞争性结合试验中，活性最高的类似物4-D表现出50倍的选择性，在HEK-293细胞的反式激活试验中表现出100倍的选择性。α选择性被推测在于苯并[d] [1,3]噻嗪环的硫原子与受体亚型结合口袋中两个具有区分作用的残基之间的相互作用。
