Synthesis and SAR of novel, 4-(phenylsulfamoyl)phenylacetamide mGlu4 positive allosteric modulators (PAMs) identified by functional high-throughput screening (HTS)

被引：26
|
作者：
Engers, Darren W. [1 ,2 ]
Gentry, Patrick R. [1 ,2 ]
Williams, Richard [1 ,2 ]
Bolinger, Julie D. [1 ]
Weaver, C. David [1 ,2 ]
Menon, Usha N. [1 ]
Conn, P. Jeffrey [1 ,2 ]
Lindsley, Craig W. [1 ,2 ,3 ]
Niswender, Colleen M. [1 ,2 ]
Hopkins, Corey R. [1 ,2 ]
机构：
[1] Vanderbilt Univ, Med Ctr, Dept Pharmacol, Nashville, TN 37232 USA
[2] Vanderbilt Program Drug Discovery, Nashville, TN 37232 USA
[3] Vanderbilt Univ, Dept Chem, Nashville, TN 37232 USA
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2010年 / 20卷 / 17期
关键词：
mGlu; Metabotropic glutamate receptor 4; Functional high-throughput screen (HTS); GLUTAMATE-RECEPTOR; 4; PARKINSONS-DISEASE; MGLUR4; PHARMACOLOGY; DISCOVERY;
D O I：
10.1016/j.bmcl.2010.07.007
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
Herein we disclose the synthesis and SAR of a series of 4-(phenylsulfamoyl)phenylacetamide compounds as mGlu(4) positive allosteric modulators (PAMs) that were identified via a functional HTS. An iterative parallel approach to these compounds culminated in the discovery of VU0364439 (11) which represents the most potent (19.8 nM) mGlu(4) PAM reported to date. (C) 2010 Elsevier Ltd. All rights reserved.
引用
收藏
页码：5175 / 5178
页数：4
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