Pharmacophore-based search, synthesis, and biological evaluation of anthranilic amides as novel blockers of the Kv1.5 channel

被引：44
|
作者：
Peukert, S [1 ]
Brendel, J [1 ]
Pirard, B [1 ]
Strübing, C [1 ]
Kleemann, HW [1 ]
Böhme, T [1 ]
Hemmerle, H [1 ]
机构：
[1] Aventis Pharma Deutschland GmbH, Med Chem & DG Cardiovasc, D-65926 Frankfurt, Germany
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2004年 / 14卷 / 11期
关键词：
Kv1.5; blockers; anthranilic amides; atrial fibrillation;
D O I：
10.1016/j.bmcl.2004.03.057
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
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.
引用
收藏
页码：2823 / 2827
页数：5
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