Design and synthesis of 4-substituted-8-(2-phenyl-cyclohexyl)-2,8-diaza-spiro[4.5]decan-1-one as a novel class of GlyT1 inhibitors:: Achieving selectivity against the μ opioid and nociceptin/orphanin FQ peptide (NOP) receptors

被引：13
作者：
Alberati, Daniela
Ceccarelli, Simona M.
Jolidon, Synese
Krafft, Eva A.
Kurt, Anke
Maier, Axel
Pinard, Emmanuel
Stalder, Henri
Studer, Deborah
Thomas, Andrew W. [1 ]
Zimmerli, Daniel
机构：
[1] F Hoffmann La Roche Ltd, Discovery Chem, Div Pharmaceut, CH-4070 Basel, Switzerland
[2] F Hoffmann La Roche Ltd, Discovery Biol, Div Pharmaceut, CH-4070 Basel, Switzerland
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2006年 / 16卷 / 16期
关键词：
GlyT1; GlyT2; NMDA; schizophrenia; transporter; glycine; spiropiperidine;
D O I：
10.1016/j.bmcl.2006.05.064
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
A novel class of 4-substituted-8-(2-phenyl-cyclohexyl)-2,8-diaza-spiro[4.5]decan-1-ones have been discovered and developed as potent and selective GlyT1 inhibitors. The molecules are devoid of activity at the GlyT2 isoform and display excellent selectivities against the mu opioid receptor as well as the nociceptin/orphanin FQ peptide (NOP) receptor. A novel, straightforward and efficient synthetic strategy for the assembly of the target molecules is also presented. (c) 2006 Elsevier Ltd. All rights reserved.
引用
收藏
页码：4305 / 4310
页数：6
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