新型双、三、四取代叔氨基类似物作为神经元烟碱型受体拮抗剂，可介导尼古丁诱导的多巴胺释放。
Novel bis-, tris-, and tetrakis-tertiary amino analogs as antagonists at neuronal nicotinic receptors that mediate nicotine-evoked dopamine release.
机构信息
Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536-0082, USA.
出版信息
Bioorg Med Chem Lett. 2011 Jan 1;21(1):88-91. doi: 10.1016/j.bmcl.2010.11.070. Epub 2010 Nov 24.
Abstract
A series of tertiary amine analogs derived from lead azaaromatic quaternary ammonium salts has been designed and synthesized. The preliminary structure-activity relationships of these new analogs suggest that such tertiary amine analogs, which potently inhibit nicotine-evoked dopamine release from rat striatum, represent drug-like inhibitors of α6-containing nicotinic acetylcholine receptors. The bis-tertiary amine analog 7 exhibited an IC(50) of 0.95 nM, while the tris-tertiary amine analog 19 had an IC(50) of 0.35 nM at nAChRs mediating nicotine-evoked dopamine release.
摘要
设计并合成了一系列衍生自先导氮杂芳基季铵盐的三级胺类似物。这些新类似物的初步结构-活性关系表明，这些强效抑制大鼠纹状体烟碱诱发多巴胺释放的三级胺类似物，是含有α6 的烟碱型乙酰胆碱受体的类药性抑制剂。双三级胺类似物 7 的 IC50 为 0.95 nM，而三三级胺类似物 19 在介导烟碱诱发多巴胺释放的 nAChRs 上的 IC50 为 0.35 nM。
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