title: Synthesis and receptor binding in trans-CD ring-fused A-CD estrogens: comparison with the cis-fused isomers.
abstract: Ligands which selectively activate only one of the estrogen receptors, ERα or ERβ, are current pharmaceutical targets. Previously, we have reported on substituted cis A-CD ligands in which the B-ring of the steroidal structure has been removed and cis refers the stereochemistry of the CD ring junction as compared to trans in estradiol. These compounds often showed good potency and selectivity for ERβ. Here we report the synthesis and binding affinities for a similar series of trans A-CD ligands, and compare them to the cis-series. Counterintuitively, trans A-CD ligands, which are structurally more closely related to the natural ligand estradiol, show weaker binding and less β-selectivity than their cis-counterparts.
authors.affiliation: Department of Chemistry, University of Ottawa, D'Iorio Hall, 10 Marie Curie St., Ottawa K1N 6N5, Canada.
authors.forename: Cristian
authors.initials: C
authors.lastname: Dabrota
authors.affiliation: Department of Chemistry, University of Ottawa, D'Iorio Hall, 10 Marie Curie St., Ottawa K1N 6N5, Canada.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Asim
authors.affiliation: Department of Chemistry, University of Ottawa, D'Iorio Hall, 10 Marie Curie St., Ottawa K1N 6N5, Canada.
authors.forename: Christine
authors.initials: C
authors.lastname: Choueiri
authors.affiliation: Department of Chemistry, University of Ottawa, D'Iorio Hall, 10 Marie Curie St., Ottawa K1N 6N5, Canada.
authors.forename: Ana
authors.initials: A
authors.lastname: Gargaun
authors.affiliation: Department of Chemistry, University of Ottawa, D'Iorio Hall, 10 Marie Curie St., Ottawa K1N 6N5, Canada.
authors.forename: Ilia
authors.initials: I
authors.lastname: Korobkov
authors.affiliation: Department of Chemistry, University of Ottawa, D'Iorio Hall, 10 Marie Curie St., Ottawa K1N 6N5, Canada.
authors.forename: Ammara
authors.initials: A
authors.lastname: Butt
authors.affiliation: Department of Chemistry, University of Illinois, Urbana, IL 61801, USA.
authors.forename: Kathryn E
authors.initials: KE
authors.lastname: Carlson
authors.affiliation: Department of Chemistry, University of Illinois, Urbana, IL 61801, USA.
authors.forename: John A
authors.initials: JA
authors.lastname: Katzenellenbogen
authors.affiliation: Department of Chemistry, Carleton University, 1125 Colonel By Dr., Ottawa K1S 5B6, Canada.
authors.forename: James S
authors.initials: JS
authors.lastname: Wright
authors.affiliation: Department of Chemistry, University of Ottawa, D'Iorio Hall, 10 Marie Curie St., Ottawa K1N 6N5, Canada. Electronic address: tony.durst@uottawa.ca.
authors.forename: Tony
authors.initials: T
authors.lastname: Durst
mesh_terms: D018360:Crystallography, X-Ray; D004305:Dose-Response Relationship, Drug; D065171:Estrogen Receptor Antagonists / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000037:antagonists & inhibitors*; D047629:Estrogen Receptor beta / Q000037:antagonists & inhibitors*; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D008968:Molecular Conformation; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D065171:Estrogen Receptor Antagonists; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D008024:Ligands
keywords: ERα; ERβ; Estrogen receptor; Ligand synthesis; β-Selectivity