N，N-二取代哌嗪：α4β2*和α7*神经元烟碱型乙酰胆碱受体的合成及亲和力
N,N-disubstituted piperazines: synthesis and affinities at alpha4beta2(*) and alpha7(*) neuronal nicotinic acetylcholine receptors.
作者信息
Chen Jianhong, Norrholm Seth, Dwoskin Linda P, Crooks Peter A, Bai Donglu
机构信息
Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 294 Tai-yuan Road, China.
出版信息
Bioorg Med Chem Lett. 2003 Jan 6;13(1):97-100. doi: 10.1016/s0960-894x(02)00849-1.
Abstract
A series of N,N-disubstituted piperazines were prepared and evaluated for binding to alpha4beta2() and alpha7() neuronal nicotinic acetylcholine receptors using rat striatum and whole brain membrane preparations, respectively. This series of compounds exhibited selectivity for alpha4beta2() nAChRs and did not interact with the alpha7() nAChRs subtype. The most potent analogues were compounds 8b and 8f (K(i)=32 microM). Thus, linking together a pyridine pi-system and a cyclic amine moiety via a piperazine ring affords compounds with low affinity, but good selectivity for alpha4beta2(*) nicotinic receptors.
摘要
制备了一系列N,N-二取代哌嗪，并分别使用大鼠纹状体和全脑膜制剂评估它们与α4β2和α7神经元烟碱型乙酰胆碱受体的结合情况。该系列化合物对α4β2烟碱型乙酰胆碱受体具有选择性，且不与α7烟碱型乙酰胆碱受体亚型相互作用。最有效的类似物是化合物8b和8f（抑制常数=32微摩尔）。因此，通过哌嗪环将吡啶π体系和环状胺部分连接在一起，可得到对α4β2*烟碱型受体具有低亲和力但良好选择性的化合物。
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