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T型钙通道阻滞剂的首个药效团假说。

First pharmacophoric hypothesis for T-type calcium channel blockers.

作者信息

Doddareddy Munikumar Reddy, Jung Hee Kyung, Lee Jae Yeol, Lee Yong Sup, Cho Yong Seo, Koh Hun Yeong, Pae Ae Nim

机构信息

Biochemicals Research Center, Korea Institute of Science and Technology, PO Box 131, Cheongryang, Seoul, 130-650, South Korea.

出版信息

Bioorg Med Chem. 2004 Apr 1;12(7):1605-11. doi: 10.1016/j.bmc.2004.01.034.

Abstract

A three-dimensional pharmacophore model was developed for T-type calcium channel blockers in order to map common structural features of highly active compounds by using CATALYST program. In the absence of three dimensional structure based information like binding mode and unavailability of more number of specific T-type calcium channel blockers, this hypothesis which consists of three hydrophobic regions, one hydrogen bond acceptor and one positive ionizable regions will act as a valuable tool in designing new ligands. Further more after the withdrawal of mibefradil, the first marketed T-type calcium channel blocker, due to the drug-drug interactions, there is an urgent need for more work in this interest.

摘要

为了通过使用CATALYST程序描绘高活性化合物的共同结构特征,开发了一种针对T型钙通道阻滞剂的三维药效团模型。由于缺乏基于三维结构的信息,如结合模式,且可获得的特定T型钙通道阻滞剂数量有限,这个由三个疏水区域、一个氢键受体和一个正离子化区域组成的假设,将成为设计新配体的有价值工具。此外,在首个上市的T型钙通道阻滞剂米贝地尔因药物相互作用撤市后,迫切需要在这方面开展更多工作。

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