Synthesis and Biological Characterization of 3-Substituted-1H-indoles as Ligands of GluN2B-Containing N-Methyl-D-aspartate Receptors

被引：18

作者：

Gitto, Rosaria ^{[1
]}

De Luca, Laura ^{[1
]}

Ferro, Stefania ^{[1
]}

Buemi, Maria Rosa ^{[1
]}

Russo, Emilio ^{[2
]}

De Sarro, Giovarnbattista ^{[2
]}

Costa, Lara ^{[3
]}

Ciranna, Lucia ^{[3
]}

Prezzavento, Orazio ^{[4
]}

Arena, Emanuela ^{[4
]}

Ronsisvalle, Simone ^{[4
]}

Bruno, Giuseppe ^{[5
]}

Chimirri, Alba ^{[1
]}

机构：

[1] Univ Messina, Dipartimento Farmacochim, I-98168 Messina, Italy

[2] Magna Graecia Univ Catanzaro, Dipartimento Med Sperimentale & Clin, I-88100 Catanzaro, Italy

[3] Univ Catania, Dipartimento Sci Biomed, Sez Fisiol, I-95125 Catania, Italy

[4] Univ Catania, Dipartimento Sci Farmaco, I-95125 Catania, Italy

[5] Univ Messina, Dipartimento Chim Inorgan Chim Analit & Chim Fis, I-98100 Messina, Italy

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2011年 / 54卷 / 24期

关键词：

NMDA ANTAGONISTS; PHARMACOLOGY; SUBUNITS; CHANNELS; BINDING; DESIGN;

D O I：

10.1021/jm2008002

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

As an extension of our studies, novel indole derivatives were rationally designed and synthesized as ligands targeted to GluN2B/NMDA receptors. The 2-(4-benzylpiperidin-1-yl)-1-(6-hydroxy-1H-indol-3-yl)ethanone (4i) and 1-(4-benzylpiperidin-l-yl)-2-(6-hydroxy-1H-indol-3-yl)ethane-1,2-dione (6i) showed high binding affinity in [H-3]ifenprodil displacement assay. By computational studies, we suggested the hypothetical interactions playing a significant role during the binding process. However, in functional and in vivo studies the most potent compound 4i did not show any activity whereas it displayed relevant affinity toward the sigma(2) receptor.

引用

页码：8702 / 8706

页数：5

共 28 条

[1]

[Anonymous], 2006, PYMOL

[2] Anti-amnesic properties of (±)-PPCC, a novel sigma receptor ligand, on cognitive dysfunction induced by selective cholinergic lesion in rats [J].

Antonini, Vuokko ;

Prezzavento, Orazio ;

Coradazzi, Marino ;

Marrazzo, Agostino ;

Ronsisvalle, Simone ;

Arena, Emanuela ;

Leanza, Giampiero .

JOURNAL OF NEUROCHEMISTRY, 2009, 109 (03) :744-754

[3] Insights into Structure-Activity Relationships and CNS Therapeutic Applications of NR2B Selective Antagonists [J].

Beinat, C. ;

Banister, S. ;

Moussa, I. ;

Reynolds, A. J. ;

McErlean, C. S. P. ;

Kassiou, M. .

CURRENT MEDICINAL CHEMISTRY, 2010, 17 (34) :4166-4190

[4] NR2B selective NMDA antagonists:: The evolution of the ifenprodil-type pharmaeophore [J].

Borza, Istvan ;

Domany, Gyorgy .

CURRENT TOPICS IN MEDICINAL CHEMISTRY, 2006, 6 (07) :687-695

[5]

CHAPMAN AG, 1984, ARZNEIMITTEL-FORSCH, V34-2, P1261

[6] Combined Strategies for the Discovery of Ionotropic Glutamate Receptor Antagonists [J].

Chimirri, Alba ;

De Luca, Laura ;

Ferro, Stefania ;

De Sarro, Giovanbattista ;

Ciranna, Lucia ;

Gitto, Rosaria .

CHEMMEDCHEM, 2009, 4 (06) :917-922

[7] Pharmacology and Therapeutic Potential of Sigma1 Receptor Ligands [J].

Cobos, E. J. ;

Entrena, J. M. ;

Nieto, F. R. ;

Cendan, C. M. ;

Del Pozo, E. .

CURRENT NEUROPHARMACOLOGY, 2008, 6 (04) :344-366

[8] A nomenclature for ligand-gated ion channels [J].

Collingridge, Graham L. ;

Olsen, Richard W. ;

Peters, John ;

Spedding, Michael .

NEUROPHARMACOLOGY, 2009, 56 (01) :2-5

[9] Mechanism of differential control of NMDA receptor activity by NR2 subunits [J].

Gielen, Marc ;

Retchless, Beth Siegler ;

Mony, Laetitia ;

Johnson, Jon W. ;

Paoletti, Pierre .

NATURE, 2009, 459 (7247) :703-U107

[10] Computational Studies to Discover a New NR2B/NMDA Receptor Antagonist and Evaluation of Pharmacological Profile [J].

Gitto, Rosaria ;

De Luca, Laura ;

Ferro, Stefania ;

Occhiuto, Francesco ;

Samperi, Stefania ;

De Sarro, Giovanbattista ;

Russo, Emilio ;

Ciranna, Lucia ;

Costa, Lara ;

Chimirri, Alba .

CHEMMEDCHEM, 2008, 3 (10) :1539-1548

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