2D-and 3D-QSAR of Tocainide and Mexiletine analogues acting as Nav1.4 channel blockers

被引：24

作者：

Carrieri, Antonio ^{[1
]}

Muraglia, Marilena ^{[1
]}

Corbo, Filomena ^{[1
]}

Pacifico, Concetta ^{[1
]}

机构：

[1] Univ Bari, Dipartimento Farmacochim, I-70125 Bari, Italy

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2009年 / 44卷 / 04期

关键词：

3D-QSAR; GRIND; Tocainide; Mexiletine; Sodium channel; GATED NA+ CHANNELS; STEREOSELECTIVE BLOCKERS; CRYSTAL-STRUCTURE; BINDING; DERIVATIVES; GRIND;

D O I：

10.1016/j.ejmech.2008.10.005

中图分类号：

R914 [药物化学];

学科分类号：

100705 [微生物与生化药学];

摘要：

Enantiomeric forms of Tocainide. Mexiletine, and structurally related local anaesthetic compounds, were analyzed with respect to their potency in blocking Na(v)1.4 channel. Structure-activity relationships based on in vitro pharmacological assays, suggested that an increase in terms of lipophilicity and/or molecular surface as well as the presence of specific polar spacers might be determinant for receptor interactions. QSAR and pharmacophore models were then used to support at 3D level this hypothesis. (C) 2008 Elsevier Masson SAS. All rights reserved.

引用

页码：1477 / 1485

页数：9

共 30 条

[1]

3-DIMENSIONAL QUANTITATIVE STRUCTURE-ACTIVITY-RELATIONSHIPS OF 5-HT RECEPTOR-BINDING DATA FOR TETRAHYDROPYRIDINYLINDOLE DERIVATIVES - A COMPARISON OF THE HANSCH AND COMFA METHODS [J].