芳杂基哌嗪基脒类化合物的设计合成及HT和NE重摄取-药学学报.PDF

药学学报 Acta Pharmaceutica Sinica 2009, 44 (3) : 303308 ·303 · 芳杂基哌嗪基脒类化合物的设计、合成及 5-HT 和NE 重摄取双重抑制活性 辉, 杨 静, 张建军, 王亚芳, 冀呈雪, 杨光中* ( 中国医学科学院、北京协和医学院 物研究所, 北京 100050) 摘要: 本文基于药效团模型的指导和课题组前期的研究结果，设计合成了一类全新结构类型的芳杂基哌嗪基 1 脒类化合物，通过 H NMR、HRMS 对化合物结构进行了确证，并完成了初步的体外 理活性评价。结果表明 这些化合物显示不同程度的5-HT 和NE 重摄取抑制活性，值得进一步研究。 关键词: 5-羟色胺; 去甲肾上腺素; 药效团模型; 双重重摄取抑制剂 中图分类号: R916.2 文献标识码:A 文章编号: 0513-4870 (2009) 03-0303-06 Design, synthesis and 5-HT/NE dual reuptake inhibitory activity of aromatic heterocyclic arylamidine derivatives * WEN Hui, YANG Jing, ZHANG Jian-jun, WANG Ya-fang, JI Cheng-xue, YANG Guang-zhong (Institute of Materia Medica, Chinese Academy of M edical Sciences Peking Union M edical College, Beij ing 100050, China) Abstract: Based on the pharmacophore information and the analysis of structure activity relationship of SSRIs and SNRIs, a series of substituted aromatic heterocyclic arylamidine derivatives were designed and synthesized in order to search for lead compounds with dual activity. All of them were new compounds, and their structures were confirmed by 1H NMR and HRMS. Preliminary in vitro pharmacological tests showed that all target compounds exhibited 5-HT reuptake inhibitory activity and some compounds exhibited NE reuptake inhibitory activity. These aromatic heterocyclic arylamidine designed can be further optimized for finding more potent 5-HT/NE dual reuptake inhibitors and antidepressant candidates as well. Key words: serotonin ; norepinephrine; pharmacophore model; dual reuptake inhib