Design and synthesis of isoform-selective phospholipase D (PLD) inhibitors. Part I: Impact of alternative halogenated privileged structures for PLD1 specificity

被引：80

作者：

Lewis, Jana A. ^{[1
]}

Scott, Sarah A. ^{[1
]}

Lavieri, Robert ^{[1
]}

Buck, Jason R. ^{[1
]}

Selvy, Paige E. ^{[1
]}

Stoops, Sydney L. ^{[1
]}

Armstrong, Michelle D. ^{[1
]}

Brown, H. Alex ^{[1
,2
]}

Lindsley, Craig W. ^{[1
,2
,3
]}

机构：

[1] Vanderbilt Univ, Med Ctr, Dept Pharmacol, Nashville, TN 37232 USA

[2] Vanderbilt Univ, Med Ctr, Dept Chem, Nashville, TN 37232 USA

[3] Vanderbilt Univ, Med Ctr, Vanderbilt Inst Chem Biol, Vanderbilt Program Drug Discovery, Nashville, TN 37232 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2009年 / 19卷 / 07期

关键词：

Phospholipase D; Cancer; Isoform; PLD1; PLD2; OVEREXPRESSION;

D O I：

10.1016/j.bmcl.2009.02.057

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

This Letter describes the synthesis and structure-activity-relationships (SAR) of isoform-selective PLD inhibitors. By virtue of the installation of alternative halogenated piperidinyl benzimidazolone privileged structures, in combination with a key ( S)-methyl group, novel PLD inhibitors with low nM potency and unprecedented levels of PLD1 isoform selectivity (similar to 1700-fold) over PLD2 were developed. (C) 2009 Elsevier Ltd. All rights reserved.

引用

页码：1916 / 1920

页数：5

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