3-甲基芬太尼和羟甲芬太尼光学异构体的量子化学和QSAR研究

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3-甲基芬太尼和羟甲芬太尼光学异构体的量子化学和QSAR研究

王红武, 王智贤, 陈凯先, 嵇汝运

中国科学院上海药物研究所, 上海 200031

收稿日期:1994-10-30 修回日期:1996-05-28 出版日期:1996-09-15 发布日期:1996-09-15

Quantum Chemistry and QSAR Studies of Optical Isomers of 3-Methylfentanyl and Ohmefentanyl

Hong-Wu Wang, Zhi-Xian Wang, Kai-Xian Chen, Ru-Yun Ji

Shanghai Institute of Materia Medica; Academia Sinica; Shanghai 200031

Received:1994-10-30 Revised:1996-05-28 Online:1996-09-15 Published:1996-09-15

摘要/Abstract

摘要： 本文利用量子化学半经验MNDO方法研究了一系列3-甲基芬太尼和羟甲芬太尼衍生物, 发现由N1和O16构成的负电中心对与受体结合十分重要, 而其3位甲基可能与受体上疏水小穴结合, 同时影响苯丙酰胺(phA)的位置和空间取向, 在此基础上使用偏最小二乘法(PLS)方法进行定量构效关系研究, 建立了良好的QSAR模型。证实主要影响活性的因素为phA的空间位置和取向、O16与受体的结合能力以及3位甲基与phA的相对位置。

关键词: 3-甲基芬太尼, 羟甲芬太尼, 光学异构体, 量子化学, QSAR

Abstract: The analgesic activities of four 3-methylfentanyl and eight ohmefentanyl optical isomers are very different. In seeking for the reason why a small change in structure leads to such a great difference in activity, we carried out quantum chemistry and QSAR investigations on these compounds. It was found that the spatial relationship between 3-methyl group and the anilidophenyl was most important. Other factors such as the net atomic charge on carbonyl oxygen and the configuration of 1-(-hydroxy also influenced the activities. PLS method was used for the construction of QSAR model. Using only 3 latent variables the correlation and predictive ability were quite satisfactory.

Key words: MNDO, QSAR, 3-Methylfentanyl derivatives, PLS

Supporting:

王红武, 王智贤, 陈凯先, 嵇汝运. 3-甲基芬太尼和羟甲芬太尼光学异构体的量子化学和QSAR研究[J]. .

Hong-Wu Wang, Zhi-Xian Wang, Kai-Xian Chen, Ru-Yun Ji. Quantum Chemistry and QSAR Studies of Optical Isomers of 3-Methylfentanyl and Ohmefentanyl[J]. .

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