Investigation of (E)-3-[4-(2-Oxo-3-aryl-chromen-4-yl)oxyphenyl]acrylic Acids as Oral Selective Estrogen Receptor Down-Regulators
| Autor: | Sébastien L. Degorce, Patrick Ple, Mickaël Maudet, Jennifer H. Pink, Rowena Callis, Andrew Bailey, Bryan Roberts, Chris De Savi, Richard A. Norman, Rémy Morgentin, Aurélien Péru, Richard Ducray, Scott W. Martin, James S. Scott, Gillian M. Lamont, Philip A. MacFaul |
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| Rok vydání: | 2015 |
| Předmět: |
Aryl
Estrogen Receptor alpha Administration Oral Down-Regulation Estrogen receptor Pharmacology Coumarin Rats Bioavailability Molecular Docking Simulation chemistry.chemical_compound chemistry Biochemistry Coumarins Cell culture Cell Line Tumor Signaling proteins Drug Discovery Animals Humans Molecular Medicine Potency Umbelliferones |
| Zdroj: | Journal of Medicinal Chemistry. 58:3522-3533 |
| ISSN: | 1520-4804 0022-2623 |
| Popis: | A novel estrogen receptor down-regulator, 7-hydroxycoumarin (5, SS5020), has been reported with antitumor effects against chemically induced mammary tumors. Here, we report on our own investigation of 7-hydroxycoumarins as potential selective estrogen receptor down-regulators, which led us to the discovery of potent down-regulating antagonists, such as 33. Subsequent optimization and removal of the 7-hydroxy group led to coumarin 59, which had increased potency and improved rat bioavailability relative to SS5020. |
| Databáze: | OpenAIRE |
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