选择性5-羟色胺再摄取抑制剂3-苯基-1-茚胺类似物的三维定量构效关系研究  

3-DQSAR Study on the Analogues of 3-phenyl-1-indan-amines as SSRIs by the Comparative Molecular Field Analysis(CoMFA)

作　　者：卢律[1] 邓萍[1] 李勤耕[1] 

机构地区：[1]重庆医科大学药学院,重庆400016

出　　处：《中国药业》2007年第5期9-11,共3页China Pharmaceuticals

摘　　要：目的建立可以提示高活性的选择性5-羟色胺再摄取抑制剂(SSRIs)3-苯基-1-茚胺类化合物分子结构信息的三维定量构效关系模型,研究结构与活性间的关系,为进一步提高药物的选择性、指导新化合物的设计提供理论依据。方法通过确定34个茚胺类化合物分子的药效构象,与模板分子进行分子叠加,利用比较分子力场分析方法(CoMFA),建立了一个选择性SSRIs的三维定量构效模型。结果该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。用此模型预测了4个SSRIs的活性,结果与试验值相符。结论该模型解释了已有的构效关系,且有较高的预测能力,系数等势图映射的受体结合部位的性质对进一步提高该类药物活性的设计具有一定的指导意义。Objective To quantitively disclose the relationship between structure and activity of a series of selective serotonin reuptake inhibitors （SSRIs） for 3-phenyl-1-indan-amines, then to build a three dimensional quantitively structure activity relationship （3- DQSAR） model for the design of novel potent drugs. Methods A 3D- QSAR model of thirty- four SSRIs was established by the comparative molecular field analysis （CoMFA）. Results The cross validation R^2 cv = 0. 660, non - cross validation R^2 = 0. 976, standard error of estimate SEE=0. 196, F= 181. 916. The activities of the four compounds were predicted by this mode and the results were compatible to actual values. Conclusion The model explains the dependence of the structures of these compounds, and possesses a high predictability and offers an approach to design the potent SSRIs.

关 键 词：药物化学 三维定量构效关系 比较分子力场分析方法 选择性5-HT再摄取抑制剂 茚胺 

分 类 号：R914.2[医药卫生—药物化学] R971.43[医药卫生—药学]