Tetrahydroisoquinoline Phenols: Selective Estrogen Receptor Downregulator Antagonists with Oral Bioavailability in Rat
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- 作者：James S. Scott ; Andrew Bailey ; Robert D. M. Davies ; Sébastien L. Degorce ; Philip A. MacFaul ; Helen Gingell ; Thomas Moss ; Richard A. Norman ; Jennifer H. Pink ; Alfred A. Rabow ; Bryan Roberts ; Peter D. Smith
- 刊名：ACS Medicinal Chemistry Letters
- 出版年：2016
- 出版时间：January 14, 2016
- 年：2016
- 卷：7
- 期：1
- 页码：94-99
- 全文大小：356K
- ISSN：1948-5875
文摘
A series of tetrahydroisoquinoline phenols was modified to give an estrogen receptor downregulator-antagonist profile. Optimization around the core, alkyl side chain, and pendant aryl ring resulted in compounds with subnanomolar levels of potency. The phenol functionality was shown to be required to achieve highly potent compounds, but unusually this was compatible with obtaining high oral bioavailabilities in rat.