Synthesis of novel arylpyrazolo corticosteroids as potential ligands for imaging brain glucocorticoid receptors

Frank Wüst, Kathryn E. Carlson, John A. Katzenellenbogen

Research output: Contribution to journalArticlepeer-review

Abstract

Corticosteroids regulate a variety of essential physiological functions, such as mineral balance and stress. The great interest in these steroids, especially the glucocorticoids, stems from roles they are thought to play in neuropsychiatric disorders, such as severe depression and anxiety. The development of glucocorticoid receptor (GR) ligands which are appropriately labeled with short-lived positron-emitting radioisotopes would allow the non-invasive in-vivo imaging and mapping of brain GRs by means of positron emission tomography (PET). In this context we have synthesized a series of novel arylpyrazolo steroids exhibiting different substitution patterns at the D-ring of the steroid skeleton, as ligands for brain GRs. Special attention was given to 4-fluorophenyl pyrazolo steroids, which are known to display high binding affinity toward the GR. The compounds were evaluated in a competitive radiometric receptor binding assay to determine their relative binding affinities (RBA) to the GR. Some compounds show good binding affinities of up to 56% in comparison to dexamethasone (100%). In initial experiments, selected candidates were labeled with the positron emitter fluorine-18 and in one case with the γ-emitter iodine-131.

Original languageEnglish (US)
Pages (from-to)177-191
Number of pages15
JournalSteroids
Volume68
Issue number2
DOIs
StatePublished - Feb 1 2003

Keywords

  • Arylpyrazolo corticosteroids
  • Glucocorticoid receptor binding
  • Positron emission tomography (PET)
  • Radiolabeling

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology
  • Pharmacology
  • Clinical Biochemistry
  • Organic Chemistry

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