Design and evaluation of fragment-like estrogen receptor tetrahydroisoquinoline ligands from a scaffold-detection approach.

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Mocklinghoff S, van Otterlo WA, Rose R, Fuchs S, Zimmermann TJ, Dominguez Seoane M, Waldmann H, Ottmann C, Brunsveld L

Design and evaluation of fragment-like estrogen receptor tetrahydroisoquinoline ligands from a scaffold-detection approach.

J Med Chem. 2011 Apr 14;54(7):2005-11. doi: 10.1021/jm1011116. Epub 2011 Mar 7.

PubMed ID
21381753 [ View in PubMed
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Abstract

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.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
EstradiolEstrogen receptor alphaEC 50 (nM)130N/AN/ADetails
EstradiolEstrogen receptor betaEC 50 (nM)280N/AN/ADetails