ICTM-Department of Chemistry, University of Belgrade, Njegoseva 12, 11000 Belgrade, Serbia.
Bioorg Med Chem Lett. 2012 Jun 15;22(12):3967-72. doi: 10.1016/j.bmcl.2012.04.098. Epub 2012 Apr 30.
It is suggested that the ratio of dopamine D(2) to 5-hydroxytryptamine 5-HT(1A) activity is an important parameter that determines the efficiency of antipsychotic drugs. Here we present the synthesis of N-{[2-(4-phenyl-piperazin-1-yl)-ethyl]-phenyl}-2-aryl-2-yl-acetamides and 1-{[2-(4-phenyl-piperazin-1-yl)-ethyl]-phenyl}-3-aryl-2-yl-ureas and their structure-activity relationship studies on dopamine D(2) and 5-hydrohytryptamine 5-HT(1A) receptors. It was shown that ligand selectivity and affinity strongly depends on their topology and the presence of a pyridyl group in the head of molecules. Molecular modeling studies using homology modeling and docking simulation revealed a rational explanation for the ligand behavior. The observed binding modes and receptor-ligand interactions provided us with a clue for optimizing the optimal selectivity towards 5-HT(1A) receptors.
有人提出，多巴胺 D（2）与 5-羟色胺 5-HT（1A）活性的比值是决定抗精神病药物效率的一个重要参数。在这里，我们介绍了 N-（[2-（4-苯基-哌嗪-1-基）-乙基]-苯基）-2-芳基-2-基-乙酰胺和 1-（[2-（4-苯基-哌嗪-1-基）-乙基]-苯基）-3-芳基-2-基-脲的合成及其对多巴胺 D（2）和 5-羟色胺 5-HT（1A）受体的构效关系研究。结果表明，配体的选择性和亲和力强烈依赖于它们的拓扑结构和分子头部吡啶基团的存在。使用同源建模和对接模拟进行的分子建模研究为配体行为提供了合理的解释。观察到的结合模式和受体-配体相互作用为我们提供了优化对 5-HT（1A）受体最佳选择性的线索。
