Design and Synthesis of Fluorescently Labeled Steroidal Antiestrogens

Publication date: Available online 21 February 2019Source: SteroidsAuthor(s): Robert N. Hanson, Nisal GajadeeraAbstractA set of derivatives of 11β-(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 11β-[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.Graphical abstractMultistep convergent synthesis provided novel fluorescently labeled steroidal antiestrogens 12a and 12b, and non-aromatic control analogs.
Source: Steroids - Category: Drugs & Pharmacology Source Type: research