Design and Evaluation of Fragment-Like Estrogen Receptor Tetrahydroisoquinoline Ligands from a Scaffold-Detection Approach
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- 作者：Sabine Mo虉cklinghoff ; Willem A. L. van Otterlo ; Rolf Rose ; Sascha Fuchs ; Tobias J. Zimmermann ; Marta Dominguez Seoane ; Herbert Waldmann ; Christian Ottmann ; Luc Brunsveld
- 刊名：Journal of Medicinal Chemistry
- 出版年：2011
- 出版时间：April 14, 2011
- 年：2011
- 卷：54
- 期：7
- 页码：2005-2011
- 全文大小：898K
- 年卷期：v.54,no.7(April 14, 2011)
- ISSN：1520-4804
文摘
A library of small tetrahydroisoquinoline ligands, previously identified via structure- and chemistry-based hierarchical organization of library scaffolds in tree-like arrangements, has been generated as novel estrogen receptor agonistic fragments via traditional medicinal chemistry exploration. The approach described has allowed for the rapid evaluation of a structure鈭抋ctivity relationship of the ligands concerning estrogen receptor affinity and estrogen receptor 尾 subtype selectivity. The structural biological insights obtained from the fragments aid the understanding of larger analogues and constitute attractive starting points for further optimization.