4-取代Fentanyl类化合物电子结构及构效关系研究

Studies on Electronic Structure and Structure-Activity Relationships of 4-Substituted-Fentanyl Derivatives

本文对十一个4-取代Fentanyl类化合物进行了量子化学(INDO)计算,研究了它们的电子结构及构效关系.结果表明,这些化合物同其他Fentanyl类化合物在主要活性部位和电子结构趋势上基本相同.酰胺氧原子是最重要的负电中心,哌啶氮原子在季铵化后发挥正电中心作用.4-取代基的极性基团可能以电荷转移作用或氢键接受体形式与受体极性部位结合,并能影响其他活性部位电子密度,另外,4-取代基的立体因素与疏水因素同生物活性相关.

The semiempirical self-consistent field MO(INDO)calculations have been undertakenfor 114-substituted-fentanyl derivatives.Electronic structure and structure-activityrelationships of these compounds were investigated.Study of the results showed thatmain active site and trend of electronic structure of these compounds are about the sameas that of another type of fentanyl compounds.Some important quantum chemical indicessuch as electron density on piperidyl nitrogen and amide oxygen correlates with biologicalactivity.Electric,steric and hydrophobic factors of 4-substituents of these compoundscorrelates with biological activity too.Polar group of 4-substituent not only can interactwith polar site of receptor by charge transfer and/or hydrogen bond formation but alsocan increase negative charge on amide oxygen.