RESUMEN
3-(3-[18F]Fluoropropyl)-6-nitroquipazine ([18F]FPNQ) as a 5-HT transporter imaging agents was designed, synthesized, and evaluated. FPNQ was selected due to its potent in vitro biological activity (K(i)=0.32 nM) in rat brain cortical membranes. The 18F-labeled FPNQ was prepared by reaction of the propyl mesylate as a precursor with tetra-n-butylammonium [18F]fluoride generated under NCA conditions. The precursor mesylate was synthesized from commercially available hydrocarbostyril in nine steps in 21% overall yield. The specific activity of the [18F]FPNQ determined by radioreceptor assay was 27.0 GBq/micromol. Tissue distribution studies in mice showed the highest uptake in the frontal cortex (5.79 %ID/g) at 60 min post-injection.
Asunto(s)
Proteínas Portadoras/síntesis química , Proteínas Portadoras/metabolismo , Glicoproteínas de Membrana/síntesis química , Glicoproteínas de Membrana/metabolismo , Proteínas de Transporte de Membrana , Proteínas del Tejido Nervioso/síntesis química , Proteínas del Tejido Nervioso/metabolismo , Quipazina/análogos & derivados , Quipazina/síntesis química , Quipazina/metabolismo , Animales , Cromatografía Líquida de Alta Presión , Espectroscopía de Resonancia Magnética , Ratones , Proteínas de Transporte de Serotonina en la Membrana Plasmática , Espectrometría de Masa por Ionización de Electrospray , Espectrometría de Masa Bombardeada por Átomos Veloces , Distribución TisularRESUMEN
Eleven 4-substituted derivatives of 6-nitroquipazine were synthesized and evaluated for their abilities to displace [3H]citalopram binding to the rat cortical synaptic membranes. Among them, 4-chloro-6-nitroquipazine was shown to possess the highest binding affinity (K(i=)0.03 nM) which was approximately 6 times higher than that of 6-nitroquipazine (K(i)=0.17 nM) itself. In this paper, we describe the syntheses of 4-substituted 6-nitroquipazine derivatives, the results of corresponding biological evaluation and the SAR study.