6-苄基氨基-3-羟基六环[6.5.0.0(3,7).0(4,12).0(5,10).0(9,13)]十三烷的结构与离子通道活性

The structure and ion channel activity of 6-benzylamino-3-hydroxyhexa-cyclo[6.5.0.0(3,7).0(4,12).0(5,10).0(9,13]tridecane.

作者信息

Malan Sarel F, Dyason Karin, Wagenaar Bianca, Van Der Walt J Jurgens, Van Der Schyf Cornelis J

机构信息

Pharmaceutical Chemistry, Potchefstroom University for Christian Higher Education, Potchefstroom, South Africa.

出版信息

Arch Pharm (Weinheim). 2003 Apr;336(2):127-33. doi: 10.1002/ardp.200390009.

DOI:10.1002/ardp.200390009

PMID:12761766

Abstract

A novel compound, 6-benzylamino-3-hydroxyhexacyclo [6.5.0.0(3, 7).0(4, 12).0(5, 10).0(9, 13)]-tridecane, was synthesized as part of an ongoing study to explore the ion channel activity of polycyclic cage amines. The known polycyclic calcium channel antagonist, 8-benzylamino-8, 11-oxapentacyclo [5.4.0.0(2, 6).0(3, 10).0(5, 9)]undecane (NGP 1-01) served as the lead compound and as a positive control for channel activity. The title compound inhibited calcium currents at test concentrations of 10 microM at depolarized membrane potentials (in the potential range where the L-type calcium channel inactivates). At the test concentrations modulating effects were also observed for sodium and the delayed rectifier potassium currents. Due to its activity at both Ca(2+) and Na(+) channels, this compound may offer utility as a cardiovascular and/or neuroprotecting agent.

摘要

作为正在进行的探索多环笼状胺离子通道活性研究的一部分，合成了一种新型化合物6-苄基氨基-3-羟基六环[6.5.0.0(3,7).0(4,12).0(5,10).0(9,13)]十三烷。已知的多环钙通道拮抗剂8-苄基氨基-8,11-氧杂五环[5.4.0.0(2,6).0(3,10).0(5,9)]十一烷（NGP 1-01）用作先导化合物和通道活性的阳性对照。在去极化膜电位（L型钙通道失活的电位范围内），标题化合物在10微摩尔的测试浓度下抑制钙电流。在测试浓度下，还观察到对钠电流和延迟整流钾电流的调节作用。由于其对Ca(2+)和Na(+)通道均有活性，该化合物可能具有作为心血管和/或神经保护剂的效用。