Zhang Y, Williams W, Bowen W D, Rice K C
Laboratory of Medicinal Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-0815, USA.
J Med Chem. 1996 Aug 30;39(18):3564-8. doi: 10.1021/jm9600813.
A series of aryl-monosubstituted arylacetamides (4-9) and arylethylenediamine (10-18) compounds were synthesized based on the structure of the high-affinity sigma ligand N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(1-pyrrolidinyl)ethylamine (2). These compounds were prepared to evaluate the effect of aromatic substitution patterns on sigma-1 and sigma-2 receptor binding affinity and selectivity. The data indicate that 10-18 possessed higher affinity than 4-9 for both sigma sites, especially when substituted with an electron-withdrawing group. The diamine compounds 10-18 were selective for sigma-1 binding sites, whereas the arylacetamide compounds 4-9 generally exhibited an increased selectivity for sigma-2 sites compared to sigma-1. No clear pattern between the orientation of aromatic substituents and the sigma binding activity was observed.
基于高亲和力σ配体N-[2-(3,4-二氯苯基)乙基]-N-甲基-2-(1-吡咯烷基)乙胺(2)的结构，合成了一系列芳基单取代芳基乙酰胺(4-9)和芳基乙二胺(10-18)化合物。制备这些化合物是为了评估芳环取代模式对σ-1和σ-2受体结合亲和力和选择性的影响。数据表明，10-18对两个σ位点的亲和力均高于4-9，尤其是当被吸电子基团取代时。二胺化合物10-18对σ-1结合位点具有选择性，而芳基乙酰胺化合物4-9与σ-1相比，通常对σ-2位点表现出更高的选择性。未观察到芳环取代基的取向与σ结合活性之间的明确规律。
