Identification and structure-activity relationships of a novel series of estrogen receptor ligands based on 7-thiabicyclo[2.2.1]hept-2-ene-7-oxide.

ABSTRACT: To develop estrogen receptor (ER) ligands having novel structures and activities, we have explored compounds in which the central hydrophobic core has a more three-dimensional topology than typically found in estrogen ligands and thus exploits the unfilled space in the ligand-binding pocket. Here, we build upon our previous investigations of 7-oxabicyclo[2.2.1]heptene core ligands, by replacing the oxygen bridge with a sulfoxide. These new 7-thiabicyclo[2.2.1]hept-2-ene-7-oxides were conveniently prepared by a Diels-Alder reaction of 3,4-diarylthiophenes with dienophiles in the presence of an oxidant and give cycloadducts with endo stereochemistry. Several new compounds demonstrated high binding affinities with excellent ERα selectivity, but unlike oxabicyclic compounds, which are transcri

SUBMITTER: Wang P 

PROVIDER: S-EPMC3297713 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature