Design and Evaluation of Fragment-Like Estrogen Receptor Tetrahydroisoquinoline Ligands from a Scaffold-Detection Approach
| Autor: | Herbert Waldmann, Marta Dominguez Seoane, Sabine Möcklinghoff, Sascha Fuchs, Willem A. L. van Otterlo, Luc Brunsveld, Tobias J. Zimmermann, Christian Ottmann, Rolf Rose |
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| Přispěvatelé: | Chemical Biology |
| Rok vydání: | 2011 |
| Předmět: |
Models
Molecular Scaffold Chemistry Stereochemistry Tetrahydroisoquinoline Estrogen Receptor alpha Estrogen receptor Small Molecule Libraries Subtype selectivity Plasma protein binding Ligands Protein Structure Tertiary Substrate Specificity chemistry.chemical_compound Drug Design Tetrahydroisoquinolines Drug Discovery Estrogen Receptor beta Molecular Medicine Estrogen receptor alpha Estrogen receptor beta |
| Zdroj: | Journal of Medicinal Chemistry, 54(7), 2005-2011. American Chemical Society |
| ISSN: | 1520-4804 0022-2623 |
| Popis: | 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 ß subtype selectivity. The structural biological insights obtained from the fragments aid the understanding of larger analogues and constitute attractive starting points for further optimization. |
| Databáze: | OpenAIRE |
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