Towards NR2B receptor selective imaging agents for PET -: synthesis and evaluation of N-[11C]-(2-methoxy)benzyl (E)-styrene-, 2-naphthyl- and 4-trifluoromethoxyphenylamidine

被引：23

作者：

Arstad, Erik

Platzer, Stefan

Berthele, Achim

Pilowsky, Lyn S.

Luthra, Sajinder K.

Wester, Hans-Juergen

Henriksen, Gjermund

机构：

[1] Hammersmith Imanet Ltd, London W12 0NN, England

[2] Tech Univ Munich, Klinikum Rechts Isar, Dept Neurol, D-81675 Munich, Germany

[3] UCL, Inst Nucl Med, London W1N 8AA, England

[4] KCL, Inst Psychiat, London SE5 8AF, England

[5] Tech Univ Munich, Klinikum Rechts Isar, Dept Nucl Med, D-81675 Munich, Germany

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2006年 / 14卷 / 18期

关键词：

PET; NMDA-NR2B; glutamate; amidine; carbon-11;

D O I：

10.1016/j.bmc.2006.05.046

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Three potent and selective C-11-labelled NR2B antagonists have been synthesized and evaluated as PET ligands. The brain uptake of the compounds in mice varied substantially and was dominated by metabolism. One compound was found to have favourable uptake and retention in the brain, as well as a binding pattern consistent with the expression of the target receptor as measured by in vitro autoradiography. However, the metabolism of the compounds tested was too rapid to allow for in vivo imaging. (c) 2006 Elsevier Ltd. All rights reserved.

引用

页码：6307 / 6313

页数：7

共 25 条

[1] COMT Val108/158 Met genotype affects the mu-opioid receptor system in the human brain:: Evidence from ligand-binding, G-protein activation and preproenkephalin mRNA expression
Berthele, A
Platzer, S
Jochim, B
Boecker, H
Buettner, A
Conrad, B
Riemenschneider, M
Toelle, TR
[J]. NEUROIMAGE, 2005, 28 (01) : 185 - 193
[2] Orally efficacious NR2B-selective NMDA receptor antagonists
Claiborne, CF
McCauley, JA
Libby, BE
Curtis, NR
Diggle, HJ
Kulagowski, JJ
Michelson, SR
Anderson, KD
Claremon, DA
Freidinger, RM
Bednar, RA
Mosser, SD
Gaul, SL
Connolly, TM
Condra, CL
Bednar, B
Stump, GL
Lynch, JJ
Macaulay, A
Wafford, KA
Koblan, KS
Liverton, NJ
[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2003, 13 (04) : 697 - 700
[3] Coughenour LL, 1997, J PHARMACOL EXP THER, V280, P584
[4] Novel N1-(benzyl)cinnamamidine derived NR2B subtype-selective NMDA receptor antagonists
Curtis, NR
Diggle, HJ
Kulagowski, JJ
London, C
Grimwood, S
Hutson, PH
Murray, F
Richards, P
Macaulay, A
Wafford, KA
[J]. BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2003, 13 (04) : 693 - 696
[5] Radiosynthesis and in vivo evaluation of [11C]Ro-647312:: a novel NR1/2B subtype selective NMDA receptor radioligand
Dollé, F
Valette, H
Demphel, S
Coulon, C
Ottaviani, M
Bottlaender, M
Kassiou, M
[J]. JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS, 2004, 47 (13) : 911 - 920
[6] The synthesis of a benzamidine-containing NR2B-selective NMDA receptor ligand labelled with tritium or fluorine-18
Hamill, TG
McCauley, JA
Burns, HD
[J]. JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS, 2005, 48 (01) : 1 - 10
[7] Haradahira T, 2005, J LABELLED COMPD RAD, V48, pS92
[8] Synthesis, in vitro and in vivo pharmacology of a C-11 labeled analog of CP-101,606, (±)threo-1-(4-hydroxyphenyl)-2-[4-hydroxy-4-(p-[11C]methoxyphenyl)piperidinol-1-propanol, as a PET tracer for NR2B subunit-containing NMDA receptors
Haradahira, T
Maeda, J
Okauchi, T
Zhang, MR
Hojo, J
Kida, T
Arai, T
Yamamoto, F
Sasaki, S
Maeda, M
Suzuki, K
Suhara, T
[J]. NUCLEAR MEDICINE AND BIOLOGY, 2002, 29 (05) : 517 - 525
[9] FURTHER CHARACTERIZATION OF [H-3] IFENPRODIL BINDING IN RAT-BRAIN
HASHIMOTO, K
MANTIONE, CR
SPADA, MR
NEUMEYER, JL
LONDON, ED
[J]. EUROPEAN JOURNAL OF PHARMACOLOGY-MOLECULAR PHARMACOLOGY SECTION, 1994, 266 (01): : 67 - 77
[10] Ionotropic and metabotropic glutamate receptor structure and pharmacology
Kew, JNC
Kemp, JA
[J]. PSYCHOPHARMACOLOGY, 2005, 179 (01) : 4 - 29

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