新的异苯骈呋喃胺类化合物的合成和抗抑郁活性初步研究  

Study on Synthesis and Anti-Depression Activity of Novel Analogues of Isobenzofuran Amine

作　　者：卢律达 申晓辉 叶继东 王以武[3] 

机构地区：[1]湖南省湘潭市中心医院,湖南湘潭411100 [2]河南豫辰精细化工有限公司,河南许昌461100 [3]重庆医科大学药学院,重庆400016

出　　处：《中国药业》2010年第23期14-16,共3页China Pharmaceuticals

摘　　要：目的为进一步提高选择性5-羟色胺再摄取抑制剂(SSRIs)的选择性和抗抑郁活性,合成具有抗抑郁活性的新的异苯骈呋喃胺类化合物。方法通过三维定量构效模型成果,指导设计并合成出新的化合物,用经典抗抑郁药理试验筛选,得到新的异苯骈呋喃胺类化合物。结果新化合物合成的总收率分别为44%,51%,40%,36%,47%;药理试验结果显示,化合物4b明显减少了小鼠的静止时间,具有显著统计学意义(P<0.05)。结论化合物4b是一种潜在的具有更高抗抑郁活性的SSRIs。Objective To enhance the selectivity and potent anti-depression activity of selective serotonin reuptake inhibitors（SSRIs） for synthetizing novel analogues of isobenzofuran amine possessing the anti-depression activity.Methods On the basis of three dimensional quantitative structure activity relationship（3D-QSAR） model by the comparative molecular field analysis（CoMFA）,to design and synthetize series of novel compounds by one of high efficiency routes,then to obtain the new active analogues from them by classic tests.Results The new compounds were obtained respectively with the overall yields of 44%,51%,40%,36% and 47%.The mice administered with the compound 4b（40 mg /kg） had obviously shorter immobility time than the blank control mice（P〈 0.05）.Conclusion The compound 4b is worthy to be further investigated in antidepressant activity as the potent SSRIs.

关 键 词：异苯骈呋喃胺 选择性5-羟色胺再摄取抑制剂 合成 小鼠悬尾试验 小鼠强迫游泳试验 

分 类 号：TQ460.3[化学工程—制药化工] R965[医药卫生—药理学]