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

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。

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

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.