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

页码：2823 / 2827

页数：5

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