title: Synthesis and evaluation of (17 alpha,20E)21-[125I]iodo-11-substituted-19-norpregna-1,3,5(10), 20-tetraene-3,17 beta-diols: the influence of 11-stereochemistry on tissue distribution of radioiodinated estrogens.
abstract: The 21-tri-n-butylstannyl derivatives of (17 alpha,20E)-11 alpha and beta-methoxy-19-norpregna-1,3,5(10),20-tetraene-3,17 beta-diol were synthesized and characterized. These compounds, as well as the 11-unsubstituted compound were converted via electrophilic ipso radioiododestannylation to the corresponding 21[125I]iodo analogs at the no-carrier-added level in 73-90% isolated radiochemical yields. The radiochemical 4c [IV alpha ME2, (17,20E)-21[125I]iodo-11 alpha-methoxy-19-norpregna-1,3, 5(10),20-tetraene-3,17 beta-diol] was evaluated in immature female rats and the results compared to those previously reported for 4a (IVE2) and 4b (IV beta ME2) to determine the influence of 11-substitution on the ability of the compounds to function as estrogen receptor-seeking agents in vivo. The results indicated that the uptake of 11 alpha-methoxy derivative in the target organ was substantially lower, of shorter duration, with a much smaller specific receptor binding component than the other two radioligands. The distribution profile of the three 17 alpha-iodovinyl estrogens paralleled that previously reported for the corresponding 17 alpha-ethynyl estrogens and this study suggests that the in vivo pharmacological results reported for the 17 alpha-ethynyl estrogens may be used to predict the in vivo behavior of the corresponding 17 alpha-iodovinyl analogs.
authors.affiliation: Section of Medicinal Chemistry, College of Pharmacy and Allied Health Professions, Northeastern University, Boston, MA.
authors.forename: R N
authors.initials: RN
authors.lastname: Hanson
authors.forename: L A
authors.initials: LA
authors.lastname: Franke
authors.forename: M L
authors.initials: ML
authors.lastname: Kaplan
mesh_terms: D000818:Animals; D004997:Ethinyl Estradiol / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D005260:Female; D007457:Iodine Radioisotopes / Q000138:chemical synthesis / Q000493:pharmacokinetics; D007553:Isotope Labeling; D015394:Molecular Structure; D009652:Norpregnenes / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D051381:Rats; D011919:Rats, Inbred Strains; D011960:Receptors, Estrogen / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014018:Tissue Distribution
chemical_list: D007457:Iodine Radioisotopes; D009652:Norpregnenes; D011960:Receptors, Estrogen; D004997:Ethinyl Estradiol; C011310:moxestrol