新的二芳基哌嗪基脒类化合物——化学合成和5-HT重摄取抑制活性  

Synthesis and 5-HT reuptake inhibition activity of biarylbenzamidine derivatives

作　　者：秦芳[1] 王娜沙[1] 杨静[1] 张建军[1] 王亚芳[1] 杨光中[1] 

机构地区：[1]中国医学科学院北京协和医学院药物研究所,北京100050

出　　处：《药学学报》2008年第6期619-625,共7页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(30572233);北京市自然科学基金资助项目(7062045).

摘　　要：为了寻找新的5-HT重摄取抑制活性的抗抑郁药,设计合成了31个哌嗪取代的二苯脒类化合物,通过1H NMR,HRMS对化合物结构进行了确证,并测定了化合物的体外5-HT重摄取抑制活性。结果表明所有化合物都有一定程度的5-HT重摄取抑制活性。其中化合物5 i、4a和5m具有较强的5-HT重摄取抑制活性,其活性与阳性对照品丙咪嗪相当或稍强,值得进一步研究。A series of biarylbenzamidine analogs were synthesized and tested for their biological activities of inhibiting the reuptake of 5-HT. All of them were new compounds, and their structures were confirmed by 1^H NMR and HRMS. Preliminary in vitro pharmacological tests showed that all target compounds exhibited 5-HT reuptake inhibition activity. Among the tested compounds, 5i, 4a and 5m exhibited potent inhibitory activity against 5-HT reuptake in vitro. It is a chance to find a better precursor of SSRIs （ selective serotonin reuptake inhibitors） for further optimization of compounds.

关 键 词：合成 哌嗪取代的二苯脒类化合物 5-HT重摄取抑制活性 抗抑郁 

分 类 号：R916.2[医药卫生—药学]