【摘要】 用量子力学方法对非极性取代的4-正丙基芬太尼和极性取代的4-甲氧甲基芬太尼及4-甲氧羰基芬太尼的电子结构和构象进行了研究.结果表明,4-取代基对提高活性的贡献表现在电性因素方面,构象变化不是主要因素.4-非极性取代基对提高活性没有贡献.4-极性取代基增加了新的负电荷集中部位,这新的负电势区域可能是同受体相互作用的一个重要辅助部位,该区域既可与受体的另一部位作用,也可能同酰胺氧原子作用于同一受体部位,无论是哪一种情况均有利于提高活性。更多还原

【Abstract】 The electronic structures and conformations of non-polar-substituted 4-n-propyl-fentanyl and polar substituted 4-methoxymethyl-fentanyl and 4-methoxycarbonyl-fentanyl were investigated by the method of quantum mechanics. The results showedthat the cause of effect of 4-substituent on biological activity not that change ofconformations but that electronic factors. The 4-non-polar-substituents have not con-tribution upon increase of activity. The 4-polar-substituents form new additionalnegative electronic region, which may be the main assistant site interacting withreceptor,the additional negative electrostatic potential region may interact with recep-tor at a new site or the site in common with amide oxygen. It is no doubt that theadditional negative electrostatic potential field generated by the 4-polar-substituentdramatically increases the analgesic activity of the fentanyl derivatives.更多还原