title: Synthesis and evaluation of 17α-(dimethylphenyl)vinyl estradiols as probes of the estrogen receptor-α ligand binding domain.
abstract: As part of our program to explore the influence of small structural modifications on the biological response of the estrogen receptor-α (ERα), we prepared and evaluated a series of mono-and di-substituted phenyl vinyl estradiols. The target compounds were prepared in 45-80% yields using the Stille coupling reaction and evaluated using competitive binding analysis with the ERα-ligand binding domain (hERα-LBD) and estrogenic activity (induction of alkaline phosphatase in Ishikawa cells). Results indicated that the 2,4- and 2,5-dimethyl derivatives, 5b and 5c, had the highest relative binding affinity (RBA=20.5 and 37.3%) and relative stimulatory activity (RSA=101.0% and 12.3%) of the di-methyl series.
authors.affiliation: Department of Chemistry and Chemical Biology, Northeastern University, 360 Huntington Avenue, Boston, MA 02115, United States. r.hanson@neu.edu
authors.forename: Robert N
authors.initials: RN
authors.lastname: Hanson
authors.forename: Emmett
authors.initials: E
authors.lastname: McCaskill
authors.forename: Pakamas
authors.initials: P
authors.lastname: Tongcharoensirikul
authors.forename: Robert
authors.initials: R
authors.lastname: Dilis
authors.forename: David
authors.initials: D
authors.lastname: Labaree
authors.forename: Richard B
authors.initials: RB
authors.lastname: Hochberg
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D001665:Binding Sites; D001667:Binding, Competitive; D045744:Cell Line, Tumor; D004958:Estradiol / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism*; D047628:Estrogen Receptor alpha / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007536:Isomerism; D008024:Ligands; D008956:Models, Chemical; D008958:Models, Molecular; D015394:Molecular Structure; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship; D014753:Vinyl Compounds / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D047628:Estrogen Receptor alpha; D008024:Ligands; D014753:Vinyl Compounds; D004958:Estradiol; D000469:Alkaline Phosphatase