Investigation of (E)-3-[4-(2-Oxo-3-aryl-chromen-4-yl)oxyphenyl]acrylic Acids as Oral Selective Estrogen Receptor Down-Regulators.

Basic Information

ID: ALA3425438

Journal: J Med Chem

Title: Investigation of (E)-3-[4-(2-Oxo-3-aryl-chromen-4-yl)oxyphenyl]acrylic Acids as Oral Selective Estrogen Receptor Down-Regulators.

Authors: Degorce SL, Bailey A, Callis R, De Savi C, Ducray R, Lamont G, MacFaul P, Maudet M, Martin S, Morgentin R, Norman RA, Peru A, Pink JH, Plé PA, Roberts B, Scott JS.

Abstract: 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.

CiteXplore: 25790336

DOI: 10.1021/acs.jmedchem.5b00066

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