Słowiński Tomasz, Stefanowicz Jacek, Wróbel Martyna Z, Herold Franciszek, Mazurek Andrzej, Pluciński Franciszek, Mazurek Aleksander P, Wolska Irena
Department of Drug Technology and Pharmaceutical Biotechnology, Medical University of Warsaw, 1 Banacha Str., 02-097 Warsaw, Poland.
Med Chem Res. 2013 Jul;22(7):3148-3153. doi: 10.1007/s00044-012-0305-6. Epub 2012 Nov 11.
The two-stages studies of structure-activity relationship for model ligands of 5HT, 5HT, and D receptors were performed. On the first stage, the pharmacophores of two potential ligands of known in vitro binding to 5HT, 5HT, D receptors and model pharmacophore of strongly interacting D receptor ligands were found and their parameters were related to affinity data. The analyzed parameters were hydrophobic, hydrophilic, aromatic, donor and acceptor of proton centers. The geometry of spatial distribution of these properties was also investigated in comparative analysis. The studied, model compounds were two 3β-acylamine derivatives of tropane. The second stage includes docking of studied compounds to D receptor model and the comparison of its quality with in vivo binding data. The obtained results are consistent with in vitro binding data and applied procedure accurate estimates the affinity of potential ligands to D receptors.
对5-羟色胺（5HT）、5HT和多巴胺（D）受体的模型配体进行了两阶段的构效关系研究。在第一阶段，发现了两种已知体外与5HT、5HT、D受体结合的潜在配体的药效基团以及与D受体配体强相互作用的模型药效基团，并将它们的参数与亲和力数据相关联。分析的参数有疏水、亲水、芳香、质子中心的供体和受体。在比较分析中还研究了这些性质的空间分布几何结构。所研究的模型化合物是两种托烷的3β-酰胺衍生物。第二阶段包括将所研究的化合物与D受体模型对接，并将其质量与体内结合数据进行比较。所得结果与体外结合数据一致，所应用的程序准确地估计了潜在配体对D受体的亲和力。
