Synthesis, structure and quantitative structure-activity relationships of sigma receptor ligands, 1-[2-(3,4-dimethoxyphenyl)ethyl]-4-(3-phenylpropyl)piperazines
Synthesis, structure and quantitative structure-activity relationships of sigma receptor ligands, 1-[2-(3,4-dimethoxyphenyl)ethyl]-4-(3-phenylpropyl)piperazines
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DOI：
10.1016/s0968-0896(97)00093-x
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发表时间：
1997-08-01
影响因子：
3.5
通讯作者：
Ishida, T
中科院分区：
文献类型：
--
作者：
Fujimura, K;Matsumoto, J;Ishida, T
合成了一组在其苯基上具有不同取代基（R-1，R-2）的标题化合物，以发现σ受体结合亲和力。在这些化合物中，2b（R-1=R-2=Cl）具有最强的sigma（1）-结合活性，而2a（R-1=R-2= HSA 4503）对sigma（1）的选择性高于sigma（2）受体。通过X射线晶体学显示，2a和2b的晶体结构相似，除了它们的丙烯部分的一个扭转角。定量构效关系研究表明，化合物对sigma（1）受体的亲和力依赖于R-1和R-2的电子结构特征，即由分子轨道方法推导出的Swain-Lupton's R或S-pi。(C)1997 Elsevier Science Ltd.
A set of the title compounds having different substituents (R-1, R-2) on their phenyl groups was synthesized to find sigma receptor binding affinity. Among the compounds, 2b (R-1=R-2=Cl) has the most potent sigma(1)-binding activity, while 2a (R-1=R-2=H SA4503) was most selective to sigma(1) over sigma(2) receptor. The crystal structures of 2a and 2b were shown, by X-ray crystallography, to be similar except for the one torsional angle of their propylene parts. Quantitative structure-activity relationship study suggested the affinity of the compounds to the sigma(1) receptor was dependent on the electronic feature, Swain-Lupton's R or S-pi that was derived by molecular orbital method, of R-1 and R-2. (C) 1997 Elsevier Science Ltd.