Review of fluorescent steroidal ligands for the estrogen receptor 1995-2018.

The development of fluorescent ligands for the estrogen receptor (ER) continues to be of interest. Over the past 20 years, most efforts have focused on appending an expanding variety of fluorophores to the B-, C- and D-rings of the steroidal scaffold. This review highlights the synthesis and evaluation of derivatives substituted primarily at the 6-, 7α- and 17α-positions, culminating with our recent work on 11ß-substituted estradiols, and proposes an approach to new fluorescent imaging agents that retain high ER affinity.

Design and synthesis of fluorescently labeled steroidal antiestrogens.

A set of derivatives of 11ß-(4-oxyphenyl)estradiol were prepared as potential fluorescent imaging agents for the evaluation of the estrogen receptor. The compounds were designed based on the established affinity and selectivity of 11ß-[4-(dimethylethoxy)phenyl]estradiol (RU39411) as an estrogen receptor (ER) antagonist. The 5-(dimethylamino) naphathalene-1-sulfonyl (dansyl) and 7-nitrobenzo[c][1,2,5] oxadiaol-4-yl (NBD) moieties were selected based on their fluorescent and physicochemical properties. A convergent synthesis was developed that culminated in the [3 + 2] copper (I) assisted alkyne-azide cycloaddition coupling of the steroidal and fluorescent components. Good yields were obtained for the intermediates and final products, and the structural variations in the steroid component will permit evaluation of ER affinity and selectivity.