N-(2-羟基-2-芳基环己基)取代的螺哌啶类化合物作为具有改善药理特性的甘氨酸转运体1拮抗剂的发现。
Discovery of N-(2-hydroxy-2-aryl-cyclohexyl) substituted spiropiperidines as GlyT1 antagonists with improved pharmacological profile.
作者信息
Ceccarelli Simona M, Pinard Emmanuel, Stalder Henri, Alberati Daniela
机构信息
F. Hoffmann-La Roche Ltd, Pharmaceutical Division Basel, Discovery Chemistry, CH-4070 Basel, Switzerland.
出版信息
Bioorg Med Chem Lett. 2006 Jan 15;16(2):354-7. doi: 10.1016/j.bmcl.2005.09.067. Epub 2005 Oct 21.
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.
在探索 N-(2-芳基环己基)取代的螺哌啶作为甘氨酸转运体 1（GlyT1）抑制剂的构效关系（SAR）过程中，发现环己基残基的 2 位引入羟基可显著改善其药理特性。特别是，实现了对孤啡肽/孤啡肽 FQ 肽和μ阿片受体结合亲和力的降低。
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