Synthesis and Biological Evaluation of N-Substituted Quinolinimides, as Potential Ligands for in Vivo Imaging Studies of -Opioid Rec
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- 作者：Thomas Bourdier ; Gé ; raldine Poisnel ; Martine Dhilly ; Jé ; rô ; me Delamare ; Joë ; l Henry ; Daniè ; le Debruyne ; Louisa Barré
- 刊名：Bioconjugate Chemistry
- 出版年：2007
- 出版时间：March 2007
- 年：2007
- 卷：18
- 期：2
- 页码：538 - 548
- 全文大小：281K
- 年卷期：v.18,no.2(March 2007)
- ISSN：1520-4812
文摘
We report here the syntheses of N-substituted quinolinimide derivatives displaying sufficient affinity and highselectivity for 
-opioid receptors. Among 9-subsituted derivatives, one showed much higher selectivity for the receptor in binding assays than the antagonist methylnaltrindole (6: Ki = 42 nM; 
/ and 
/ > 238 on ratbrain membranes) and antagonist properties. This compound was labeled with carbon-11 (t1/2 = 20.4 min) as apotential radioligand for the noninvasive assessment of opioid receptors in vivo with positron emission tomography(PET). A high yielding radiosynthesis of [11C]-6, based on the [11C]methyl introduction on the pyridine moietyby a Stille reaction, was described (radiochemical yield = 60 ± 10%, specific activities = 0.8 to 1.5 Ci/mol).The in vivo pharmacological profile in rats indicated that the radiotracer crossed the blood-brain barrier but wasnot stable and underwent rapid degradation in both plasma and brain. No specific binding was consequentlyrevealed.
-opioid receptors. Among 9-subsituted derivatives, one showed much higher selectivity for the receptor in binding assays than the antagonist methylnaltrindole (6: Ki = 42 nM; / and / > 238 on ratbrain membranes) and antagonist properties. This compound was labeled with carbon-11 (t1/2 = 20.4 min) as apotential radioligand for the noninvasive assessment of opioid receptors in vivo with positron emission tomography(PET). A high yielding radiosynthesis of [11C]-6, based on the [11C]methyl introduction on the pyridine moietyby a Stille reaction, was described (radiochemical yield = 60 ± 10%, specific activities = 0.8 to 1.5 Ci/mol).The in vivo pharmacological profile in rats indicated that the radiotracer crossed the blood-brain barrier but wasnot stable and underwent rapid degradation in both plasma and brain. No specific binding was consequentlyrevealed.