Estrogen receptor ligands.: II.: Discovery of benzoxathiins as potent, selective estrogen receptor α modulators

被引：92

作者：

Kim, S

Wu, JY

Birzin, ET

Frisch, K

Chan, W

Pai, LY

Yang, YT

Mosley, RT

Fitzgerald, PMD

Sharma, N

Dahllund, J

Thorsell, AG

DiNinno, F

Rohrer, SP

Schaeffer, JM

Hammond, ML

机构：

[1] Merck Res Labs, Dept Med Chem, Rahway, NJ 07065 USA

[2] Merck Res Labs, Dept Atherosclerosis, Rahway, NJ 07065 USA

[3] Merck Res Labs, Dept Endocrinol, Rahway, NJ 07065 USA

[4] Karo Bio AB, Novum, S-14157 Huddinge, Sweden

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2004年 / 47卷 / 09期

关键词：

D O I：

10.1021/jm034243o

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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 a 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.

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页码：2171 / 2175

页数：5

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