3-甲基芬太尼衍生物与μ阿片受体的相互作用模型

Interaction models of 3-methylfentanyl derivatives with mu opioid receptors.

作者信息

Rong S B, Zhu Y C, Jiang H L, Wang Q M, Zhao S R, Chen K X, Ji R Y

机构信息

Shanghai Institute of Materia Medica, Chinese Academy of Sciences, China.

出版信息

Zhongguo Yao Li Xue Bao. 1997 Mar;18(2):128-32.

PMID:10072963

Abstract

AIM

To study the interaction model of 3-methylfentanyl derivatives with mu opioid receptor.

METHODS

After a systematic conformational search, a three-dimensional quantitative structure-activity relationship study was carried out with comparative molecular field analysis (CoMFA).

RESULTS

The 6 CoMFA models had good predictive values and each model corresponded to the minimum-energy conformations of 13 compounds studied; 2) The important geometric parameters of mu pharmacophore d1 (A), d2 (A), d3 (A), d4 (A), d5 (A), and d6 (A) were 5.2, 5.4, 4.9, 10.6, 10.2, and 5.8 in Model A; 5.2, 6.5, 3.6, 10.6, 11.6, and 5.8 in Model B; 5.2, 4.6, 4.9, 11.6, 9.2, and 6.5 in Model C; 5.2, 5.4, 4.9, 10.5, 10.3, and 5.8 in Model D; 3.6, 5.4, 4.9, 5.7, 7.5, and 5.7 in Model E; 5.2, 4.7, 4.9, 11.2, 9.5, and 6.4 in Model F, respectively.

CONCLUSIONS

The several bioactive conformations of fentanyl analogs possibly existed and did not need to be the absolute minimum-energy conformation, each of which was involved in the interaction with mu opioid receptor.

摘要

目的

研究3-甲基芬太尼衍生物与μ阿片受体的相互作用模式。

方法

在进行系统的构象搜索后，采用比较分子场分析（CoMFA）进行三维定量构效关系研究。

结果

1）6个CoMFA模型具有良好的预测值，每个模型对应所研究的13种化合物的最低能量构象；2）模型A中μ药效基团d1（Å）、d2（Å）、d3（Å）、d4（Å）、d5（Å）和d6（Å）的重要几何参数分别为5.2、5.4、4.9、10.6、10.2和5.8；模型B中分别为5.2、6.5、3.6、10.6、11.6和5.8；模型C中分别为5.2、4.6、4.9、11.6、9.2和6.5；模型D中分别为5.2、5.4、4.9、10.5、10.3和5.8；模型E中分别为3.6、5.4、4.9、5.7、7.5和5.7；模型F中分别为5.2、4.7、4.9、11.2、9.5和6.4。