Pharmacophore-based search, synthesis, and biological evaluation of anthranilic amides as novel blockers of the Kv1.5 channel
Pharmacophore-based search, synthesis, and biological evaluation of anthranilic amides as novel blockers of the Kv1.5 channel
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DOI：
10.1016/j.bmcl.2004.03.057
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发表时间：
2004-06-07
影响因子：
2.7
通讯作者：
Hemmerle, H
中科院分区：
文献类型：
--
作者：
Peukert, S;Brendel, J;Hemmerle, H
搜索新的，有效的Kv1.5阻滞剂的基础上，采用基于药效团的虚拟筛选方法的邻氨基苯甲酰胺支架。的合成和结构活性关系（SAR）相对于抑制Kv1.5通道进行了讨论。最有效的化合物显示Kv1.5的亚微摩尔抑制，对HERG通道无显著影响。此外，证明化合物X在大鼠中具有良好的口服生物利用度。(C)2004 Elsevier Ltd.保留所有权利。
The search for novel, potent Kv1.5 blockers based on an anthranilic amide scaffold employing a pharmacophore-based virtual screening approach is described. The synthesis and structure-activity relationships (SAR) with respect to inhibition of the Kv1.5 channel are discussed. The most potent compounds display sub-micromolar inhibition of Kv1.5 and no significant effect on the HERG channel. In addition, good oral bioavailability is demonstrated for compound X in rats. (C) 2004 Elsevier Ltd. All rights reserved.