Abstract
In our effort to develop imaging agents for brain glucocorticoid receptors, we have prepared several novel glucocorticoids possessing a 2-methylsulfanyl-acetyl side chain. The synthesis was accomplished via a Mitsunobu reaction with thiobenzoic acid starting from cortisol, prednisolone, dexamethasone and triamcinolone acetonide to give the corresponding S-thiobenzoates in 75-82% yield. Subsequent saponification and reaction with methyl iodide afforded C-21 methylthioethers in 68-82% yield. All compounds were tested in an in vitro glucocorticoid receptor-binding assay. Triamcinolone acetonide-based compound 12 showed promising binding affinity of 144% relative to dexamethasone (100%). Compound 12 was selected for radiolabeling with the short-lived positron emitter carbon-11. The radiolabeling was carried out starting from S-thiobenzoate 8 and in situ formation of the corresponding sodium thiolate, which was further reacted with [11C]methyl iodide. The obtained radiochemical yield was 20-30%. The specific activity was determined to be 20-40 GBq/μmol at the end-of-synthesis, and the radiochemical purity exceeded 98%.
Original language | English (US) |
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Pages (from-to) | 69-76 |
Number of pages | 8 |
Journal | Steroids |
Volume | 73 |
Issue number | 1 |
DOIs | |
State | Published - Jan 2008 |
Keywords
- Carbon-11
- Glucocorticoid receptor binding
- Mitsunobu reaction
- Positron-emission-tomography (PET)
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Endocrinology
- Pharmacology
- Clinical Biochemistry
- Organic Chemistry