N-(3-苯丙基)哌嗪类σ_1受体配体的3D-QSAR研究

3D-QSAR STUDY OF N-(3-PHENYLPROPYL) PIPERAZINE TYPE OF σ1 RECEPTOR LIGANDS

采用比较分子力场(CoMFA)分析法和比较分子相似性指数(CoMSIA)分析法,对34个N-(3-苯丙基)哌嗪类σ1受体配体进行三维定量构效关系(3D-QSAR)研究,建立了具有较强预测能力的3D-QSAR模型.并利用Gaussian 03程序,采用B3LYP/6-31G(d)方法,探索了化合物分子的前线轨道与分子结构的关系.新设计的化合物的体外受体结合分析结果与该模型预测的数据一致,此结果为进一步研究σ1受体-配体的相互作用模型以及设计高亲和力的哌嗪类σ1受体配体提供了参考.

3D-QSAR of 34 N-（3-phenylpropyl） piperazine type of σ1 receptor ligands was performed with comparative molecular fields analysis （CoMFA） and comparative molecular similarity index analysis （CoMSIA）. 3D-QSAR models with different conformations were established. The frontier orbits of the above ligands were investigated with B3LYP/6-31G（d） using Gaussian 03 software. The in vitro Ki values of two newly designed compounds showed good agreements with predictions. These data indicate that established models show strong predictability. This will be useful in further investigation of σ1 receptor-ligand interactions and in designing new piperazine ligands with high affinity for σ1 receptors.