Synthesis and structure-activity relationships of a series of 4-methoxy-3-(piperidin-4-yl)oxy benzamides as novel inhibitors of the presynaptic choline transporter

被引：3
作者：
Bollinger, Sean R. [1 ,3 ,4 ]
Engers, Darren W. [1 ,3 ,4 ]
Ennis, Elizabeth A. [1 ]
Wright, Jane [1 ]
Locuson, Charles W. [1 ,3 ,4 ]
Lindsley, Craig W. [1 ,2 ,3 ,4 ]
Blakely, Randy D. [1 ,5 ]
Hopkins, Corey R. [1 ,2 ,3 ,4 ]
机构：
[1] Vanderbilt Univ, Med Ctr, Dept Pharmacol, Nashville, TN 37232 USA
[2] Vanderbilt Univ, Dept Chem, Nashville, TN 37232 USA
[3] Vanderbilt Univ, Med Ctr, Vanderbilt Ctr Neurosci Drug Discovery, Nashville, TN 37232 USA
[4] Vanderbilt Specialized Chem Ctr Probe Dev MLPCN, Nashville, TN 37232 USA
[5] Vanderbilt Univ, Med Ctr, Dept Psychiat, Nashville, TN 37232 USA
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2015年 / 25卷 / 08期
关键词：
MLPCN; ML352; Choline transporter; CHT; Structure-activity relationship; HIGH-AFFINITY UPTAKE; ACETYLCHOLINE SYNTHESIS;
D O I：
10.1016/j.bmcl.2015.02.058
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
The synthesis and SAR of 4-methoxy-3-(piperidin-4-yl) benzamides identified after a high-throughput screen of the MLPCN library is reported. SAR was explored around the 3-piperidine substituent as well as the amide functionality of the reported compounds. Starting from the initial lead compounds, 1-7, iterative medicinal chemistry efforts led to the identification of ML352 (10m). ML352 represents a potent and selective inhibitor of CHT based on a drug-like scaffold. (C) 2015 Elsevier Ltd. All rights reserved.
引用
收藏
页码：1757 / 1760
页数：4
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