物理化学学报 >> 1989, Vol. 5 >> Issue (06): 681-687.doi: 10.3866/PKU.WHXB19890608

研究论文 上一篇    下一篇

芬太尼类化合物与阿片受体相互作用的构象分析

李玉林; 连洪寿; 胡建国; 陈常英; 陈冀胜; 徐筱杰; 关玥; 罗宇; 唐有祺   

  1. 中国人民解放军药物化学研究所; 北京大学物理化学研究所
  • 收稿日期:1988-04-04 修回日期:1988-12-14 发布日期:1989-12-15
  • 通讯作者: 李玉林

CONFORMATIONAL ANALYSIS OF THE μ-OPIATE RECEPTOR AGONIST FENTANYL DERIVATIVES

Li Yulin; Lian Hongshou; Hu Jianguo; Chen Changying; Chen Jisheng; Xu Xiaojie; Guan Yue; Luo Yu; Tang Youqi   

  1. Institute of Pharmaceutical Chemistry; PLA; Beijing; Institute of Physical Chemistry; Peking University
  • Received:1988-04-04 Revised:1988-12-14 Published:1989-12-15
  • Contact: Li Yulin

摘要: 本文用X光衍射结晶学, 计算机辅助构象分析和分子图形学方法, 对芬太尼类μ型阿片受体激动剂中七个典型代表物进行了研究。结果表明, 芬太尼类化合物哌啶环4位丙酰苯胺基位置与生物活性有关。4-取代和顺式3-甲基芬太尼类化合物的晶体结构是一个能量较为合理的体系, 在该体系下的构象有可能是生物活性构象, 即哌啶环1-位苯乙基为伸展构象, 哌啶环4-位扭角τ_4(C_(11)—C_(12)—N_(15)—C_(16))为100°左右时有利于与受体相互作用。并在构象分析和分子图形拟合的基础上, 提出了芬太尼类化合物与阿片受体之间相互作用的结构要求。

Abstract: X-ray crystallography and computer-assisted conformational analysis and computer graphics studies were performed for seven Fentanyl-type potent agonist of opiate receptor. The results obtained demonstrate that there is a good agreement between the experimentally determined (by X-ray) and the calculated (by DPCILO) conformation of Fentanyl derivatives. The orientation of the N-phenylpropanamide with respect to piperidine ring plays an important role in the binding of Fentanyl-type analgeties to the opiate receptor.
When the N-phenethyl substituent is the antiperiplanar conformation and torsion angle (C_(11)—C_(12)—N_(15)—C(16)) is about 100°, Fentanyl derivatives may interact equally well with the recetor. On the basis of conformational analysis and molecular graphics fit the model for the requirements of the receptor has also been discussed.