N-(4-[18F]-fluoropyridin-2-yl)-N-{2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl}carboxamides as analogs of WAY100635. New PET tracers of serotonin 5-HT1A receptors

被引：6
|
作者：
Garcia, Gonzalo [1 ]
Abet, Valentina [1 ]
Alajarin, Ramon [1 ]
Alvarez-Builla, Julio [1 ]
Delgado, Mercedes [2 ]
Garcia-Garcia, Luis [2 ]
Bascunana-Almarcha, Pablo [2 ]
Pena-Salcedo, Carmen [3 ]
Kelly, James [3 ]
Pozo, Miguel A. [2 ,3 ]
机构：
[1] Univ Alcala, Dept Quim Organ, Madrid 28871, Spain
[2] Inst Pluridisciplinar UCM, CAI Cartog Cerebral, Madrid 28040, Spain
[3] Inst Tecnol PET, Madrid 28040, Spain
来源：
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2014年 / 85卷
关键词：
5-HT1A; Positron emission tomography; Fluorine-18; Radioligand; N-(4-[F-18]-fluoropyridin-2-yl)-N-{2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl}carboxamides; NUCLEOPHILIC AROMATIC-SUBSTITUTION; POSITRON-EMISSION-TOMOGRAPHY; IN-VIVO; RADIOACTIVE METABOLITES; TISSUE DISTRIBUTION; ARYL HALIDES; HUMAN PLASMA; BRAIN; WAY-100635; RADIOLIGAND;
D O I：
10.1016/j.ejmech.2014.07.096
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
N-(4-[F-18]-fluoropyridin-2-yl)-N-{2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl}carboxamides were prepared by labeling their 4-nitropyridin-2-yl precursors through nitro substitution by the F-18 anion. In vitro and in vivo tests showed that the cyclohexanecarboxamide derivative is a reversible, selective and high affinity 5-HT1A receptor antagonist (IC50 = 0.29 nM, k(i) = 0.18 nM) with high brain uptake, slow brain clearance and stability to defluorination when compared with conventional standards. This PET radioligand is a promising candidate for an improved in vivo quantification of 5-HT1A receptors in neuropsychiatric disorders. (C) 2014 Published by Elsevier Masson SAS.
引用
收藏
页码：795 / 806
页数：12
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