【作者】 卢律；

【导师】 李勤耕；

【作者基本信息】 重庆医科大学 ， 药物化学， 2007， 硕士

【摘要】 目的:进一步提高一种选择性5-HT重摄取抑制剂(SSRIs)的选择性和抗抑郁活性。方法:通过比较分子力场分析方法(CoMFA),建立有较高的预测能力的苯茚胺类似物抗抑郁活性的三维定量构效模型,研究其结构与活性间的关系,指导设计并优化合成出新的化合物,然后用小鼠悬尾实验进行初步的抗抑郁药理活性的筛选,得到具有抗抑郁活性的新的苯茚胺类似物。结果:该三维定量构效模型的交叉验证相关系数R2CV=0.660,非交叉验证相关系数R2=0.976,标准偏差SEE=0.196,F=181.916;合成新化合物的总收率分别为38%,44%,40%,并经过红外光谱、质谱、核磁共振氢谱对其结构进行了表征;小鼠悬尾实验结果显示化合物4b明显减少了悬尾小鼠的静止时间[(70±30)s,(73±48)s,(66±31)s],与实验对照组相比具有显著统计学意义(P<0.05)。结论:运用该模型指导设计、合成出了新的化合物,活性化合物4b可能是潜在的一种新的SSRIs,值得进一步研究。更多还原

【Abstract】 AIM To enhance the selectivity and potent anti-depression activity of one kind of selective serotonin reuptake inhibitors (SSRIs). METHODS To quantitively disclose the relationship between structure and actitivety of a series of selective serotonin reuptake inhibitors(SSRIs) for 3-Phenyl -1-indan-amines,and build a three dimensional Quantitative structure activity relationship(3D-QSAR) model for the design of novel potent drugs by the comparative molecular field analysis(CoMFA). then to design and synthesis a series of novel compounds by one of high efficiency routes. The last to obtain new active analogues from them by mouse tail suspension tests. RESULT About 3D-QSAR model ,the cross validation R2CV= 0.660 , non-crossvalidation R2=0.976,standard error of estimate SEE=0.196, F=181.916. The structure of the target compounds were verified by IR,1H-NHR and MS spectra ,and obtained respectively with overall yields of 38%,44% and 40%.The mice that were administered with the compound 4b(40mg/kg) had obviously shorter immobility time than the blank control mice (P<0.05) in mouse tail suspension tests. CONCLUSION The model possesses a high predicta- -bility and offers an approach to design the potent SSRIs, and the compound 4b is worthy to be further investigated in antidepressant activity as SSRIs.更多还原