Novel bis-, tris-, and tetrakis-tertiary amino analogs as antagonists at neuronal nicotinic receptors that mediate nicotine-evoked dopamine release.
Novel bis-, tris-, and tetrakis-tertiary amino analogs as antagonists at neuronal nicotinic receptors that mediate nicotine-evoked dopamine release.
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新型双、三和四叔氨基类似物作为神经元烟碱受体的拮抗剂，介导尼古丁诱发的多巴胺释放。
DOI：
10.1016/j.bmcl.2010.11.070
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发表时间：
2011
影响因子：
2.7
通讯作者：
Crooks,PeterA
中科院分区：
文献类型：
--
作者：
Zhang,Zhenfa;Zheng,Guangrong;Pivavarchyk,Marharyta;Deaciuc,AGabriela;Dwoskin,LindaP;Crooks,PeterA
设计并合成了一系列氮杂芳族铅季铵盐衍生的叔胺类似物。这些新类似物的初步构效关系表明，这些叔胺类似物能有效地抑制尼古丁引起的大鼠纹状体多巴胺释放，是含有α6的烟碱型乙酰胆碱受体的类药物抑制剂。双叔胺类似物7的IC50为0.95 nM，而三叔胺类似物19在nAChRs介导尼古丁诱发的多巴胺释放时的IC50为0.35 nM。
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 IC50of 0.95nM, while the tris-tertiary amine analog 19 had an IC50of 0.35nM at nAChRs mediating nicotine-evoked dopamine release.