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
相关论文
共 50 条
  • [21] Selective targeting of melanoma using N-(2-diethylaminoethyl) 4-[18F]fluoroethoxy benzamide (4-[18F]FEBZA): a novel PET imaging probe
    Garg, Pradeep K.
    Nazih, Rachid
    Wu, Yanjun
    Grinevich, Vladimir P.
    Garg, Sudha
    EJNMMI RESEARCH, 2017, 7
  • [22] Synthesis and in vivo evaluation of [O-methyl-11C] 2-(4-methoxyphenyl)-N-(4-methylbenzyl)-N-(1-methyl-piperidin-4-yl)acetamide as as imaging probe for 5-HT2A receptors
    Prabhakaran, Jaya
    Parsey, Ramin V.
    Majo, Vattoly J.
    Van Heertum, Ronald L.
    Mann, J. John
    Kumar, J. S. Dileep
    JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS, 2006, 49 (12) : 1069 - 1077
  • [23] Synthesis and in vivo evaluation of [18F]N-(2-benzofuranylmethyl)-N′-[4-(2-fluoroethoxy)benzyl]piperazine, a novel σ1 receptor PET imaging agent
    Moussa, Iman A.
    Banister, Samuel D.
    Giboureau, Nicolas
    Meikle, Steven R.
    Kassiou, Michael
    BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2011, 21 (22) : 6820 - 6823
  • [24] 2-Amino-3-(1-(4-(4-(2-methoxyphenyl) piperazine-1-yl)butyl)-1H-1,2,3-triazol-4-yl) propanoic acid: synthesized, 99mTc-tricarbonyl labeled, and bioevaluated as a potential 5HT1A receptor ligand
    Hassanzadeh, Leila
    Erfani, Mostafa
    Ebrahimi, Seyed Esmaeil Sadat
    JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS, 2012, 55 (10) : 371 - 376
  • [25] N-[18F]4′-fluorobenzylpiperidin-4yl(2-fluorophenyl) acetamide ([18F]FBFPA):: A potential fluorine-18 labeled PET radiotracer for imaging sigma-1 receptors in the CNS
    Mach, RH
    Gage, HD
    Buchheimer, N
    Huang, YS
    Kuhner, R
    Wu, L
    Morton, TE
    Ehrenkaufer, RL
    SYNAPSE, 2005, 58 (04) : 267 - 274
  • [26] Synthesis, radiolabeling and in vivo evaluation of [11C](R)-1-[4-[2-(4-methoxyphenyl)phenyl piperazin-1-yl]-3-(2-pyrazinyloxy)-2-propanol, a potential PET radioligand for the 5-HT7 receptor
    Hansen, Hanne D.
    Lacivita, Enza
    Di Pilato, Pantaleo
    Herth, Matthias M.
    Lehel, Szabolcs
    Ettrup, Anders
    Andersen, Valdemar L.
    Dyssegaard, Agnete
    De Giorgio, Paola
    Perrone, Roberto
    Berardi, Francesco
    Colabufo, Nicola Antonio
    Niso, Mauro
    Knudsen, Gitte M.
    Leopoldo, Marcello
    EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2014, 79 : 152 - 163
  • [27] N-(4-Cyanotetrahydro-2H-pyran-4-yl) and N-(1-Cyanocyclohexyl) Derivatives of 1,5-Diarylpyrazole-3-carboxamides Showing High Affinity for 18 kDa Translocator Protein and/or Cannabinoid Receptors
    Donohue, Sean R.
    Dannals, Robert F.
    Halldin, Christer
    Pike, Victor W.
    JOURNAL OF MEDICINAL CHEMISTRY, 2011, 54 (08) : 2961 - 2970
  • [28] Synthesis and in vitro evaluation of no-carrier-added 2-(3-(4-(4-[18F]fluorobenzyl)piperazin-1-yl)propyl)benzo[d]thiazole, a potential dopamine D4 receptor radioligand
    Li Gu-Cai
    Zhang Ru
    Xia Jiao-yun
    RADIOCHIMICA ACTA, 2016, 104 (12) : 897 - 903
  • [29] Synthesis and Evaluation of 4-Halogeno-N-[4-[6-(isopropylamino)pyrimidin-4-yl]-1,3-thiazol-2-yl]-N-[11C]methylbenzamide for Imaging of Metabotropic Glutamate 1 Receptor in Melanoma
    Fujinaga, Masayuki
    Xie, Lin
    Yamasaki, Tomoteru
    Yui, Joji
    Shimoda, Yoko
    Hatori, Akiko
    Kumata, Katsushi
    Zhang, Yiding
    Nengaki, Nobuki
    Kawamura, Kazunori
    Zhang, Ming-Rong
    JOURNAL OF MEDICINAL CHEMISTRY, 2015, 58 (03) : 1513 - 1523
  • [30] 1-(4-[18F]Fluorobenzyl)-4-[(tetrahydrofuran-2-yl)methyl]piperazine: A Novel Suitable Radioligand with Low Lipophilicity for Imaging σ1 Receptors in the Brain
    He, Yingfang
    Xie, Fang
    Ye, Jiajun
    Deuther-Conrad, Winnie
    Cui, Bixiao
    Wang, Liang
    Lu, Jie
    Steinbach, Jorg
    Brust, Peter
    Huang, Yiyun
    Lu, Jie
    Jia, Hongmei
    JOURNAL OF MEDICINAL CHEMISTRY, 2017, 60 (10) : 4161 - 4172
12345