title: Synthesis and evaluation of 2-halogenated-1,1-bis(4-hydroxyphenyl)-2-(3-hydroxyphenyl)-ethylenes as potential estrogen receptor-targeted radiodiagnostic and radiotherapeutic agents.
abstract: A series of three 1,1-bis(4-hydroxyphenyl)-2-(3-hydroxyphenyl)-ethylene derivatives was prepared and evaluated as potential estrogen receptor imaging agents. The compounds display high binding affinity compared to estradiol, with the 2-iodo and 2-bromo-derivatives expressing higher affinity than the parent 2-nonhalogenated derivative. Evaluation in immature female rats also indicate that the compounds were all full estrogenic agonists with potencies in the same order of activity (I∼Br>H). Computational analysis of the interactions between the ligands and ERα-LBD demonstrated positive contribution of halide to binding properties. In preparation for studies using the radiohalogenated analogs, the corresponding protected 2-(tributylstannyl) derivative was prepared and converted to the corresponding 2-iodo-product.
authors: Department of Chemistry and Chemical Biology, Northeastern University, 360 Huntington Avenue, Boston, MA 02115, United States.
authors: Robert N
authors: RN
authors: Hanson
authors: Department of Chemistry and Chemical Biology, Northeastern University, 360 Huntington Avenue, Boston, MA 02115, United States.
authors: Pakamas
authors: P
authors: Tongcharoensirikul
authors: Department of Chemistry and Chemical Biology, Northeastern University, 360 Huntington Avenue, Boston, MA 02115, United States.
authors: Kelton
authors: K
authors: Barnsley
authors: Department of Chemistry and Chemical Biology, Northeastern University, 360 Huntington Avenue, Boston, MA 02115, United States.
authors: Mary Jo
authors: MJ
authors: Ondrechen
authors: The Ben May Institute for Cancer Research, The University of Chicago, 5846 S. Maryland Avenue, Chicago, IL 60637, United States.
authors: Alun
authors: A
authors: Hughes
authors: The Ben May Institute for Cancer Research, The University of Chicago, 5846 S. Maryland Avenue, Chicago, IL 60637, United States.
authors: Eugene R
authors: ER
authors: DeSombre
mesh_terms: D000818:Animals; D060326:Chemistry Techniques, Synthetic; D047628:Estrogen Receptor alpha / Q000737:chemistry / Q000378:metabolism*; D005030:Ethylenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism* / Q000627:therapeutic use; D005260:Female; D054879:Halogenation; D008024:Ligands; D008958:Models, Molecular; D057054:Molecular Imaging; D017434:Protein Structure, Tertiary; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism* / Q000627:therapeutic use; D051381:Rats
chemical_list: D047628:Estrogen Receptor alpha; D005030:Ethylenes; D008024:Ligands; D019275:Radiopharmaceuticals; C036216:ethylene
keywords: Auger; Nonsteroidal estrogens; Relative binding affinity; Synthesis; Uterotrophic growth