一系列4-甲氧基-3-(哌啶-4-基)氧基苯甲酰胺作为突触前胆碱转运体新型抑制剂的合成及其构效关系
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.
作者信息
Bollinger Sean R, Engers Darren W, Ennis Elizabeth A, Wright Jane, Locuson Charles W, Lindsley Craig W, Blakely Randy D, Hopkins Corey R
机构信息
Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Vanderbilt Specialized Chemistry Center for Probe Development (MLPCN), Nashville, TN 37232, USA.
Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
出版信息
Bioorg Med Chem Lett. 2015 Apr 15;25(8):1757-1760. doi: 10.1016/j.bmcl.2015.02.058. Epub 2015 Feb 28.
Abstract
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.
摘要
报道了在对MLPCN文库进行高通量筛选后鉴定出的4-甲氧基-3-(哌啶-4-基)苯甲酰胺的合成及构效关系。围绕所报道化合物的3-哌啶取代基以及酰胺官能团对构效关系进行了探索。从最初的先导化合物1-7开始，经过反复的药物化学研究，确定了ML352（10m）。基于类药物骨架，ML352是一种有效的、选择性的胆碱转运体（CHT）抑制剂。
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