关键词: 解热镇痛药, 量子化学, 芬太尼, 阿片, 构效关系, 能级, 电子密度, 波函数, 电子结构, 分子轨道理论

The semiempirical SCF MO (INDO) calcns. have been undertaken for 11 4-substituted fentanyl derivatives I (R = CO2Me, COMe, CH2OMe, COEt, CO2Et, CH2OH, CO2CH2CH:CH2, CO2CHMe2, CH2OEt, CO2Pr, CO2CH2Ph). Electronic structure and structure-activity relationships of these compounds were investigated. The results showed that the active sites and electronic structures of these compounds were similar to those of other fentanyl compounds Some important quantum chem. indexes, such as electron d. of the piperidyl nitrogen and of the amide oxygen, were correlated with biol. activity. Elec., steric and hydrophobic factors of the 4-substituents of these compounds were also correlated with biol. activity. Polar groups on the 4-substituents not only can interact with polar sites of the receptor by charge transfer and/or hydrogen bond formation, but also can increase the neg. charge on the amide oxygen.

Key words: ANTIPYRETICS AND ANALGESICS, QUANTUM CHEMISTRY, FENTANYLUM, OPIUM, STRUCTURE ACTIVITY RELATIONSHIP, ENERGY LEVELS, ELECTRON DENSITY, WAVE FUNCTIONS, ELECTRONIC STRUCTURE, MOLECULAR ORBITAL THEORY