Microwave-enhanced nucleophilic fluorination in the synthesis of fluoropyridyl derivatives of [3,2-c]pyrazolo-corticosteroids, potential glucocorticoid receptor-mediated imaging agents.

Fluoropyridyl derivatives of [3,2-c]pyrazolo-corticosteroids have high affinity for the glucocorticoid receptor (GR) and are highly active glucocorticoids. They are thus considered to be excellent candidates for PET imaging of GR containing tissues when labeled with fluorine-18 (t(1/2)=110 min). Previously reported syntheses of these fluorinated glucocorticoids were accomplished by conventional thermal nucleophilic halogen exchange reactions with chloropyridyl precursors.

Synthesis of halogen-substituted pyridyl and pyrimidyl derivatives of [3,2-c]pyrazolo corticosteroids: strategies for the development of glucocorticoid receptor mediated imaging agents.

Ligands for the glucocorticoid receptor labeled with high-energy isotopes are highly desired for their potential applications in nuclear medical studies of the brain where the dysregulation of this receptor system is thought to be involved in various neurodegenerative disorders. Analogues of the glucocorticoid cortivazol have previously been prepared as target compounds for labeling with high-energy isotopes. However, the phenyl rings of arylpyrazoles of this type are not sufficiently activated for nucleophilic substitution reactions that are generally required for the synthesis of radiohalogenated analogues.