A novel estrogen receptor ligand template

• Published in: Bioorganic & medicinal chemistry letters 2003-06, Vol.13 (11), p.1919-1922
• Main Authors: Sibley, Robert, Hatoum-Mokdad, Holia, Schoenleber, Robert, Musza, Laszlo, Stirtan, William, Marrero, Diana, Carley, William, Xiao, Hong, Dumas, Jacques
• Format: Article
• Language: English
• Subjects: Alkenes - chemical synthesis; Alkenes - metabolism; Alkenes - pharmacology; Biological and medical sciences; Bridged Bicyclo Compounds, Heterocyclic - chemical synthesis; Bridged Bicyclo Compounds, Heterocyclic - metabolism; Bridged Bicyclo Compounds, Heterocyclic - pharmacology; Cell Line, Tumor; Estradiol - pharmacology; Hormones. Endocrine system; Humans; Inhibitory Concentration 50; Ligands; Medical sciences; Membrane Proteins - agonists; Membrane Proteins - metabolism; Pharmacology. Drug treatments; Presenilin-2; Raloxifene Hydrochloride - pharmacology; Receptors, Estrogen - antagonists & inhibitors; Receptors, Estrogen - metabolism
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/S0960-894X(03)00307-X

Three synthetic routes towards a novel estrogen receptor ligand template based on a rigid bicyclo-[3.3.1]-nonene core have been investigated. The prototype compound exhibits potent binding at the ERβ receptor and promising estrogen receptor subtype selectivity. Three synthetic routes towards a novel estrogen receptor ligand template based on a rigid bicyclo-[3.3.1]-nonene core have been investigated. The successful route employs Diels–Alder ring formation followed by trans-annular cyclization through an enolate intermediate. The prototype compound 3 exhibits potent binding at the ERβ receptor with promising selectivity against ERα, and is an agonist in MCF-7 cells.