| Autor: |
Matarrese, M., Moresco, R. M., Cappelli, A., Anzini, M., Vomero, S., Simonelli, P., Verza, E., Magni, F., Sudati, F., Soloviev, D., Todde, S., Carpinelli, A., Kienle, M. G., Fazio, F. |
| Zdroj: |
Journal of Medicinal Chemistry; February 2001, Vol. 44 Issue: 4 p579-585, 7p |
| Abstrakt: |
The novel quinoline-2-carboxamide derivatives N-[methyl-11C]-3-methyl-4-phenyl-N-(phenylmethyl)quinoline-2-carboxamide ([11C]4), (±)-N-[methyl-11C]-3-methyl-N-(1-methylpropyl)-4-phenylquinoline-2-carboxamide ([11C]5), and (±)-N-[methyl-11C]-3-methyl-4-(2-fluorophenyl)-N-(1-methylpropyl)quinoline-2-carboxamide ([11C]6) were labeled with carbon-11 (t1/2 = 20.4 min, β+ = 99.8%) as potential radioligands for the noninvasive assessment of peripheral benzodiazepine type receptors (PBR) in vivo with positron emission tomography (PET). The radiosynthesis consisted of N-methylation of the desmethyl precursors 3-methyl-4-phenyl-N-(phenylmethyl)quinoline-2-carboxamide (4a), (±)-3-methyl-N-(1-methylpropyl)-4-phenylquinoline-2-carboxamide (5a), and (±)-4-(2-fluorophenyl)-3-methyl-N-(1-methylpropyl)quinoline-2-carboxamide (6a) with either [11C]methyl iodide or [11C]methyl triflate in the presence of tetrabutylammonium hydroxide or potassium hydroxide in dimethylformamide. The radioligands [11C]4, [11C]5, and [11C]6 were synthesized with over 99% radiochemical purity in 30 min, 30 ± 5% radiochemical yield, calculated at the end of synthesis (EOS) non-decay-corrected, and 2.5 ± 1.2 Ci/μmol of specific radioactivity. Inhibition studies in rats following intravenous pre-administration of 1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinolinecarboxamide (PK 11195, 1) showed high specific binding to PBR of [11C]4, [11C]5, and [11C]6 in heart, lung, kidney, adrenal gland, spleen, and brain. The biological data suggest that [11C]5, [11C]6, and particularly [11C]4 are promising radioligands for PBR imaging in vivo with PET. |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
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