Stereochemical probes for the estrogen receptor: Synthesis and receptor binding of (17α, [formula omitted])-21-phenyl-19-norpregna-1,3,5(10), 20-tetraene-3,17β-diols

• Published in: Steroids Vol. 61; no. 12; pp. 718 - 722
• Main Authors: Hanson, Robert N., Herman, Lee W., Fiaschi, Rita, Napolitano, Elio
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.12.1996; Elsevier Science
• Subjects: Binding Sites; Binding, Competitive; Biological and medical sciences; Cell receptors; Cell structures and functions; Estradiol - analogs & derivatives; Estradiol - chemistry; Estradiol - metabolism; Fundamental and applied biological sciences. Psychology; Hormone receptors. Growth factor receptors. Cytokine receptors. Prostaglandin receptors; Models, Molecular; Molecular and cellular biology; Molecular Structure; receptor binding; Receptors, Estrogen - chemistry; Receptors, Estrogen - metabolism; Structure-Activity Relationship; styryl estradiol; synthesis; synthesis; receptor binding; styryl estradiol; Binding capacity; Substitution; Estrogen; Stereochemistry; Sex steroid hormone; Estradiol; Ovarian hormone; Hormonal receptor
• ISSN: 0039-128X; 1878-5867
• DOI: 10.1016/S0039-128X(96)00201-2

Previous studies from our laboratory using 17α- E- and 17α- Z-halovinyl and phenylthiovinyl estradiols demonstrated a marked preference for the Z stereochemistry and a significant steric tolerance for the Z-vinyl substituent. To further explore the extent of that stereochemical preference and steric tolerance we have prepared stereoselectively the 17α- E- and 17α- Z-phenylvinyl estradiols ( E- and Z-styrylestradiols). The results, in addition to demonstrating a facile preparation of the target compounds, supported the previously observed stereochemical and steric effects. The relative binding affinities for the Z isomer were 3–4-fold greater than the E isomer at both 4°C and 25°C, and only one-half to one-fourth those of estradiol under similar conditions. The developing model for ligand-accessible space within the estrogen receptor suggests that Z-phenylvinyl estradiols may provide interesting and useful probes for mapping the receptor.