Abstract

Aim 1 is to synthesize 18F-labeled androgens for Positron Emission Tomography (PET) imaging of prostate cancer. The steroids include an active androgen as well as prohormones that are metabolically protected to maximize the biological signal. These steroids, labeled at C-7alpha with 18F, will be synthesized and tested for androgen receptor mediated concentration in the prostate of rats and rabbits.
Aim 2 is to synthesize 18F and 123I labeled pyridyl and pyrimidyl N-substituted pyrazolo steroids based on the active glucorcorticoid, cortivazol. These steroids, containing N-activated leaving groups in their heterocyclic ring system, are designed specifically for isotope exchange reactions. The steroids are intended as PET or Single Photon Emission Tomography (SPECT) agents for imaging the glucocorticoid receptor rich region of the brain, the hippocampus.
Aim 3 is to synthesize and test analogs of E2 that are potent estrogens and yet enzymatically labile which cause them to be converted rapidly into inactive metabolites. They are designed for use as local estrogens.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
2R01CA037799-17
Application #
6258495
Study Section
Biochemical Endocrinology Study Section (BCE)
Program Officer
Menkens, Anne E
Project Start
1984-08-01
Project End
2006-01-31
Budget Start
2001-03-01
Budget End
2002-01-31
Support Year
17
Fiscal Year
2001
Total Cost
$301,449
Indirect Cost

  Institution

Name
Yale University
Department
Obstetrics & Gynecology
Type
Schools of Medicine
DUNS #
082359691
City
New Haven
State
CT
Country
United States
Zip Code
06520

  Publications

Bowlby, Deborah A; Brown, Theodore J; Hochberg, Richard B et al. (2016) In vitro Autoradiographic Analysis of Regional Changes in Estrogen Receptor Alpha in the Brains of Cycling Female Rats. Neuroendocrinology 103:538-51
Hanson, Robert N; Hua, Edward; Hendricks, J Adam et al. (2012) Synthesis and evaluation of 11?-(4-substituted phenyl) estradiol analogs: transition from estrogen receptor agonists to antagonists. Bioorg Med Chem 20:3768-80
Hanson, Robert N; McCaskill, Emmett; Tongcharoensirikul, Pakamas et al. (2012) Synthesis and evaluation of 17?-(dimethylphenyl)vinyl estradiols as probes of the estrogen receptor-? ligand binding domain. Steroids 77:471-6
Olmsted, Sandra L; Tongcharoensirikul, Pakamas; McCaskill, Emmett et al. (2012) Synthesis and evaluation of 17?-E-20-(heteroaryl)norpregn-1,3,5(10),20 tetraene-3,17?-diols [17?-(heteroaryl)vinyl estradiols] as ligands for the estrogen receptor-? ligand binding domain (ER?-LBD). Bioorg Med Chem Lett 22:977-9
Haddad, Terra; Gershman, Rachel; Dilis, Robert et al. (2012) Synthesis and evaluation of 4-(substituted styryl/alkenyl)-3,5-bis(4-hydroxyphenyl)-isoxazoles as ligands for the estrogen receptor. Bioorg Med Chem Lett 22:5999-6003
Hanson, Robert N; Kirss, Rein; McCaskill, Emmett et al. (2012) Targeting the estrogen receptor with metal-carbonyl derivatives of estradiol. Bioorg Med Chem Lett 22:1670-3
Hanson, Robert N; Hua, Edward; Labaree, David et al. (2012) Convergent synthesis of a steroidal antiestrogen-mitomycin C hybrid using ""click"" chemistry. Org Biomol Chem 10:8501-8
Nettles, Kendall W; Bruning, John B; Gil, German et al. (2008) NFkappaB selectivity of estrogen receptor ligands revealed by comparative crystallographic analyses. Nat Chem Biol 4:241-7
McCarthy, Thomas L; Hochberg, Richard B; Labaree, David C et al. (2007) 3-ketosteroid reductase activity and expression by fetal rat osteoblasts. J Biol Chem 282:34003-12
Kahn, Michael G C; Konde, Emmanuel; Dossou, Francis et al. (2006) Microwave-enhanced nucleophilic fluorination in the synthesis of fluoropyridyl derivatives of [3,2-c]pyrazolo-corticosteroids, potential glucocorticoid receptor-mediated imaging agents. Bioorg Med Chem Lett 16:3454-8

Showing the most recent 10 out of 53 publications