摘要
对芬太尼、３－甲基芬太尼的４个以及羟甲芬太尼的８个立体异构体进行了系统构象搜寻，并用比较分子力场分析（ＣｏＭＦＡ）方法研究其三维定量构效关系（３Ｄ－ＱＳＡＲ），从中得到６组与预测能力极高的ＣｏＭＦＡ模型相对应的可能活性构象．将上述６组可能活性构象分别对接到事先构建的μ阿片受体模型中，得到１组可能性最大的活性构象；且不是最低能量构象．
Systematic conformational searches were performed for the 13 studied compounds(including fentanyl,4 stereoisomers of 3 methylfentanyl and 8 stereoisomers of ohmefentanyl),which led to 55 series of minimum energy conformations.The 6 groups of possible bioactive conformations,corresponding to the 6 CoMFA models with good predictive ability,were derived from three dimensional quantitative structure activity relationship(3D QSAR)studies on the above 55 series of conformations with comparative molecular field analysis(CoMFA).Through docking the above possible bioactive conformations into the 3D structural model of μ opioid receptor constructed by us,the most possible bioactive conformations were derived for the 13 studied compounds,which are not their global minimum energy conformations.The results are helpful for the investigating the ligand receptor interaction and designing the higher selective ligands for the μ opioid receptor.
出处
《中国药物化学杂志》
CAS
CSCD
1997年第2期115-120,共6页
Chinese Journal of Medicinal Chemistry
基金
国家自然科学基金
关键词
3-甲基芬太尼
衍生物
构象分析
药理学
methylfentanyl derivatives
conformational analysis
comparative molecular field analysis
moleculardocking
μ opioid receptor
bioactive conformation
