色氨醇衍生的恶唑并哌啶酮内酰胺：一种作为NMDA受体拮抗剂的活性化合物的鉴定。
Tryptophanol-derived oxazolopiperidone lactams: identification of a hit compound as NMDA receptor antagonist.
作者信息
Pereira Nuno A L, Sureda Francesc X, Esplugas Roser, Pérez Maria, Amat Mercedes, Santos Maria M M
机构信息
Instituto de Investigação do Medicamento (iMed.ULisboa), Faculdade de Farmácia, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal.
Pharmacology Unit, Faculty of Medicine and Health Sciences, Universitat Rovira i Virgili, c./St. Llorenç 21, 43201 Reus (Tarragona), Spain.
出版信息
Bioorg Med Chem Lett. 2014 Aug 1;24(15):3333-6. doi: 10.1016/j.bmcl.2014.05.105. Epub 2014 Jun 11.
N-Methyl-D-aspartate receptors (NMDAR) exacerbated activation leads to neuron death through a phenomenon called excitotoxicity. These receptors are implicated in several neurological diseases (e.g., Alzheimer and Parkinson) and thus represent an important therapeutic target. We herein describe the study of enantiopure tryptophanol-derived oxazolopiperidone lactams as NMDA receptor antagonists. The most active hit exhibited an IC50 of 63.4 μM in cultured rat cerebellar granule neurons thus being 1.5 fold more active than clinically approved NMDA antagonist amantadine (IC50=92 μM).
N-甲基-D-天冬氨酸受体（NMDAR）的过度激活会通过一种称为兴奋毒性的现象导致神经元死亡。这些受体与多种神经疾病（如阿尔茨海默病和帕金森病）有关，因此是一个重要的治疗靶点。我们在此描述了对映体纯的色醇衍生的恶唑并哌啶酮内酰胺作为NMDA受体拮抗剂的研究。最具活性的化合物在培养的大鼠小脑颗粒神经元中表现出63.4 μM的IC50，因此比临床批准的NMDA拮抗剂金刚烷胺（IC50 = 92 μM）活性高1.5倍。
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