Stereochemical probes for the estrogen receptor: synthesis and receptor binding of (17 alpha,20E/Z)-21-phenyl-19-norpregna-1,3,5(10), 20-tetraene-3,17 beta-diols. 1996

R N Hanson, and L W Herman, and R Fiaschi, and E Napolitano
Department of Pharmaceutical Sciences, Bouve College of Pharmacy and Health Sciences, Northeastern University, Boston 02115, USA.

Previous studies from our laboratory using 17 alpha-E- and 17 alpha-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 17 alpha-E- and 17 alpha-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 degrees C and 25 degrees 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.

UI MeSH Term Description Entries
D008958 Models, Molecular Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures. Molecular Models,Model, Molecular,Molecular Model
D011960 Receptors, Estrogen Cytoplasmic proteins that bind estrogens and migrate to the nucleus where they regulate DNA transcription. Evaluation of the state of estrogen receptors in breast cancer patients has become clinically important. Estrogen Receptor,Estrogen Receptors,Estrogen Nuclear Receptor,Estrogen Receptor Type I,Estrogen Receptor Type II,Estrogen Receptors Type I,Estrogen Receptors Type II,Receptor, Estrogen Nuclear,Receptors, Estrogen, Type I,Receptors, Estrogen, Type II,Nuclear Receptor, Estrogen,Receptor, Estrogen
D004958 Estradiol The 17-beta-isomer of estradiol, an aromatized C18 steroid with hydroxyl group at 3-beta- and 17-beta-position. Estradiol-17-beta is the most potent form of mammalian estrogenic steroids. 17 beta-Estradiol,Estradiol-17 beta,Oestradiol,17 beta-Oestradiol,Aerodiol,Delestrogen,Estrace,Estraderm TTS,Estradiol Anhydrous,Estradiol Hemihydrate,Estradiol Hemihydrate, (17 alpha)-Isomer,Estradiol Monohydrate,Estradiol Valerate,Estradiol Valeriante,Estradiol, (+-)-Isomer,Estradiol, (-)-Isomer,Estradiol, (16 alpha,17 alpha)-Isomer,Estradiol, (16 alpha,17 beta)-Isomer,Estradiol, (17-alpha)-Isomer,Estradiol, (8 alpha,17 beta)-(+-)-Isomer,Estradiol, (8 alpha,17 beta)-Isomer,Estradiol, (9 beta,17 alpha)-Isomer,Estradiol, (9 beta,17 beta)-Isomer,Estradiol, Monosodium Salt,Estradiol, Sodium Salt,Estradiol-17 alpha,Estradiol-17beta,Ovocyclin,Progynon-Depot,Progynova,Vivelle,17 beta Estradiol,17 beta Oestradiol,Estradiol 17 alpha,Estradiol 17 beta,Estradiol 17beta,Progynon Depot
D001665 Binding Sites The parts of a macromolecule that directly participate in its specific combination with another molecule. Combining Site,Binding Site,Combining Sites,Site, Binding,Site, Combining,Sites, Binding,Sites, Combining
D001667 Binding, Competitive The interaction of two or more substrates or ligands with the same binding site. The displacement of one by the other is used in quantitative and selective affinity measurements. Competitive Binding
D013329 Structure-Activity Relationship The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D015394 Molecular Structure The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds. Structure, Molecular,Molecular Structures,Structures, Molecular

Related Publications

R N Hanson, and L W Herman, and R Fiaschi, and E Napolitano
October 1988, Journal of medicinal chemistry,
R N Hanson, and L W Herman, and R Fiaschi, and E Napolitano
January 1989, International journal of radiation applications and instrumentation. Part B, Nuclear medicine and biology,
R N Hanson, and L W Herman, and R Fiaschi, and E Napolitano
August 1986, Journal of medicinal chemistry,
R N Hanson, and L W Herman, and R Fiaschi, and E Napolitano
March 1969, Journal of medicinal chemistry,
Copied contents to your clipboard!