title: Iodinated and fluorinated steroid 2'-aryl-[3,2-c] pyrazoles as potential glucocorticoid receptor imaging agents.
abstract: We have synthesized several halogenated steroids as potential glucocorticoid receptor mediated imaging agents. These compounds are analogs of aryl-pyrazolo steroids, similar to the potent glucocorticoid, cortivazol. Compounds containing the halogens, iodine, bromine, and fluorine, as well as the E- and Z-iodovinyl side chain at the para position of 2'-phenyl-11 beta,17,21-trihydroxy-16 alpha-methyl-20-oxo-pregn-4-eno[3,2-c] pyrazole were prepared. They were tested as ligands for the glucocorticoid receptor by competition for the binding of [3H]dexamethasone and for glucocorticoid potency by the induction of alkaline phosphatase in HeLa cells. None of the iodinated steroids were good ligands for the glucocorticoid receptor or potent glucocorticoids. The bromo analog was only slightly better than the iodinated steroids as a ligand, and it had a potency in the HeLa cell assay about half that of dexamethasone. The fluoro analog good binding to the glucocorticoid receptor and was a very potent glucocorticoid, approximately seven times that of dexamethasone. Consequently, it appears that the fluoro steroid, 2'-(4-fluorophenyl)-11 beta,17,21-trihydroxy-16 alpha-methyl-20-oxo-pregn-4-eno[3,2-c] pyrazole, when labeled with 18F, would make an excellent glucocorticoid receptor-mediated imaging agent for positron emission tomography.
authors.affiliation: Department of Chemistry, State University of New York, Old Westbury, USA.
authors.forename: R M
authors.initials: RM
authors.lastname: Hoyte
authors.forename: D C
authors.initials: DC
authors.lastname: Labaree
authors.forename: J M
authors.initials: JM
authors.lastname: Fede
authors.forename: C
authors.initials: C
authors.lastname: Harris
authors.forename: R B
authors.initials: RB
authors.lastname: Hochberg
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D003907:Dexamethasone / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008099:Liver / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D016339:Spectrometry, Mass, Fast Atom Bombardment; D013055:Spectrophotometry, Infrared
chemical_list: D011720:Pyrazoles; D011965:Receptors, Glucocorticoid; D003907:Dexamethasone