Development of 3-substituted-1H-indole derivatives as NR2B/NMDA receptor antagonists

被引：32

作者：

Gitto, Rosaria ^{[1
]}

De Luca, Laura ^{[1
]}

Ferro, Stefania ^{[1
]}

Citraro, Rita ^{[2
]}

De Sarro, Giovambattista ^{[2
]}

Costa, Lara ^{[3
]}

Ciranna, Lucia ^{[3
]}

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 Fisiol, I-95125 Catania, Italy

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2009年 / 17卷 / 04期

关键词：

NR2B/NMDA antagonist; Molecular modeling; Anticonvulsant activity; Patch clamp; Binding affinity; NMDA RECEPTOR; NR2B SUBUNIT; BINDING; DOMAIN;

D O I：

10.1016/j.bmc.2008.12.058

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：

A combined ligand-based and structure-based approach has previously allowed us to identify NR2B/NMDA receptor antagonists containing indole scaffold. In order to further explore the main structure activity relationships of this class of derivatives we herein report the design, synthesis and biological evaluation of new analogues. Some derivatives demonstrated to produce significant anticonvulsant properties and NMDA antagonism. The most active of them (3d) showed NR2B binding affinity equipotent to that of ifenprodil. These results were also corroborated by computational studies. (C) 2008 Elsevier Ltd. All rights reserved.

引用

页码：1640 / 1647

页数：8

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