TY - JOUR
T1 - Synthesis of novel arylpyrazolo corticosteroids as potential ligands for imaging brain glucocorticoid receptors
AU - Wüst, Frank
AU - Carlson, Kathryn E.
AU - Katzenellenbogen, John A.
N1 - Funding Information:
The authors thank Prof. Dr. G. Stöcklin for helpful discussions. Financial support to FW by the Deutsche Forschungsgemeinschaft and to JAK and KEC by a grant from the Department of Energy (DE FG02 86ER60401) is gratefully acknowledged.
PY - 2003/2/1
Y1 - 2003/2/1
N2 - 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.
AB - 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.
KW - Arylpyrazolo corticosteroids
KW - Glucocorticoid receptor binding
KW - Positron emission tomography (PET)
KW - Radiolabeling
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U2 - 10.1016/S0039-128X(02)00171-X
DO - 10.1016/S0039-128X(02)00171-X
M3 - Article
C2 - 12606009
AN - SCOPUS:0037330692
SN - 0039-128X
VL - 68
SP - 177
EP - 191
JO - Steroids
JF - Steroids
IS - 2
ER -