Discovery of N-(2-hydroxy-2-aryl-cyclohexyl) substituted spiropiperidines as GlyT1 antagonists with improved pharmacological profile

被引：23

作者：

Ceccarelli, SM ^{[1
]}

Pinard, E ^{[1
]}

Stalder, H ^{[1
]}

Alberati, D ^{[1
]}

机构：

[1] F Hoffmann La Roche & Co Ltd, Pharmaceut Res, Discovery Chem, CH-4070 Basel, Switzerland

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2006年 / 16卷 / 02期

关键词：

GlyT1; GlyT2; NMDA; schizophrenia; transporter; spiropiperidine;

D O I：

10.1016/j.bmcl.2005.09.067

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

During SAR exploration of N-(2-aryl-cyclohexyl) substituted spiropiperidine as GlyT1 inhibitors, it was found that introduction of an hydroxy group in position 2 of the cyclohexyl residue considerably improves the pharmacological profile. In particular, reduction of the binding affinity at the nociceptin/orphanin FQ peptide and the mu opioid receptors was achieved. (c) 2005 Elsevier Ltd. All rights reserved.

引用

页码：354 / 357

页数：4

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