Synthesis and in vivo evaluation of [(11)C]CGP62349, a new GABA(B) receptor antagonist.
This paper describes the radiosynthesis of [(11)C]CGP62349, a potential ligand to assess GABA(B) receptors in vivo. (11)C was introduced by O-methylation of the corresponding des-methyl precursor, namely CGP67780. The final product was obtained with a reliable method in good yield. The radioligand was tested in monkey, revealing negligible blood-brain barrier penetration and brain uptake, thus prompting us to search for a new target structure with a better lipophilicity.
Todde
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CNR-INB, University of Milano-Bicocca, Scientific Institute H San Rafaele, Via Olgettina 60, Milano, Italy. sergiot@mednuc.hsr.it
Moresco
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RM
Fröstl
W
W
Stampf
P
P
Matarrese
M
M
Carpinelli
A
A
Magni
F
F
Galli Kienle
M
M
Fazio
F
F
D000818:Animals; D001565:Benzoates / Q000097:blood / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics*; D001812:Blood-Brain Barrier / Q000187:drug effects; D001921:Brain / Q000098:blood supply / Q000000981:diagnostic imaging / Q000378:metabolism*; D002250:Carbon Radioisotopes / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D005260:Female; D058788:GABA-B Receptor Antagonists; D006847:Hydrocarbons, Iodinated / Q000737:chemistry; D008024:Ligands; D008254:Macaca nemestrina; D013058:Mass Spectrometry; D009943:Organophosphorus Compounds / Q000097:blood / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D010721:Phosphinic Acids / Q000737:chemistry; D011849:Radioactive Tracers; D011869:Radioligand Assay; D018080:Receptors, GABA-B / Q000378:metabolism; D014055:Tomography, Emission-Computed
D001565:Benzoates; C114540:CGP 62349; C417906:CGP 67780; D002250:Carbon Radioisotopes; D058788:GABA-B Receptor Antagonists; D006847:Hydrocarbons, Iodinated; D008024:Ligands; D009943:Organophosphorus Compounds; D010721:Phosphinic Acids; D011849:Radioactive Tracers; D018080:Receptors, GABA-B; C014055:methyl iodide