Design and Evaluation of Fragment-Like Estrogen Receptor Tetrahydroisoquinoline Ligands from a Scaffold-Detection Approach

作者：Mocklinghoff Sabine; van Otterlo Willem A L; Rose Rolf; Fuchs Sascha; Zimmermann Tobias J; Seoane Marta Dominguez; Waldmann Herbert; Ottmann Christian; Brunsveld Luc^*

来源：Journal of Medicinal Chemistry, 2011, 54(7): 2005-2011.

DOI：10.1021/jm1011116

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 activity relationship of the ligands concerning estrogen receptor affinity and estrogen receptor beta subtype selectivity. The structural biological insights obtained from the fragments aid the understanding of larger analogues and constitute attractive starting. points for further optimization.

• 出版日期2011-4-14