Benzo[7]annulene-based GluN2B selective NMDA receptor antagonists: Surprising effect of a nitro group in 2-position

被引：16

作者：

Gawaskar, Sandeep ^{[1
,2
,3
]}

Schepmann, Dirk ^{[1
]}

Bonifazi, Alessandro ^{[4
]}

Robaa, Dina ^{[5
]}

Sippl, Wolfgang ^{[5
]}

Wuensch, Bernhard ^{[1
,3
]}

机构：

[1] Univ Munster, Inst Pharmazeut & Med Chem, D-48149 Munster, Germany

[2] NRW Grad Sch Chem, D-48149 Munster, Germany

[3] Univ Munster, Cells In Mot Cluster Excellence EXC CiM 1003, D-48149 Munster, Germany

[4] Univ Camerino, Scuola Sci Farmaco & Prod Salute, I-62032 Camerino, Italy

[5] Univ Halle Wittenberg, Inst Pharmazeut & Med Chem, D-06120 Halle, Saale, Germany

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2015年 / 25卷 / 24期

关键词：

NMDA receptor; GluN2B antagonists; 2-Nitrobenzo[7]annulen-7-amines; Structure affinity relationships; Selectivity; Conformational restriction; Docking studies; D-ASPARTATE RECEPTOR; IN-VITRO; PHARMACOLOGICAL EVALUATION; SUBUNIT ARRANGEMENT; ALZHEIMERS-DISEASE; NR2B SUBUNIT; IFENPRODIL; AFFINITY; LIGANDS; POTENT;

D O I：

10.1016/j.bmcl.2015.10.076

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Benzo[7]annulen-7-amines 7 without further polar substituents have been reported as conformationally restricted Ro 25-6981 analogs and show unexpectedly high GluN2B affinity. Herein the corresponding 2-NO2 derivatives 8 were synthesized and pharmacologically evaluated. NO2 derivatives 8 show 5- to 10-fold higher GluN2B affinity than the unsubstituted ligands 7. Docking studies of ligands 7c and 8c reveal an important contribution of the 2-NO2-substituent in determining the binding pose and modulating the GluN2B affinity. (C) 2015 Elsevier Ltd. All rights reserved.

引用

页码：5748 / 5751

页数：4

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