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

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