Bis-quinolinium cyclophanes:: toward a pharmacophore model for the blockade of apamin-sensitive SKCa channels in sympathetic neurons

被引：16

作者：

Galanakis, D ^{[1
]}

Ganellin, CR

Chen, JQ

Gunasekera, D

Dunn, PM

机构：

[1] Aristotle Univ Thessaloniki, Sch Pharm, Dept Pharmaceut Chem, Thessaloniki 54124, Greece

[2] UCL, Dept Chem, London WC1E 6BT, England

[3] UCL, Dept Pharmacol, London WC1E 6BT, England

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2004年 / 14卷 / 16期

关键词：

quinolinium; cyclophane; pharmacophore; SK3; channel; apamin; conformation; synperiplanar; centroid;

D O I：

10.1016/j.bmcl.2004.06.011

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The synthesis, pharmacological evaluation, and molecular modeling studies of unsymmetrical bis-alkylene bis-quinolinium cyclophanes and xylylene-alkylene bis-quinolinium cyclophanes is described. Two important structural features of the pharmacophore for SKCa channel blockade have been identified. These are (i) an optimum distance of ca. 5.8 Angstrom between the centroids of the pyridinium rings of the two quinolinium groups and (ii) a preference for conformations having the quinolinium groups in a synperiplanar orientation. (C) 2004 Elsevier Ltd. All rights reserved.

引用

页码：4231 / 4235

页数：5

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