物理化学学报 >> 1990, Vol. 6 >> Issue (01): 17-22.doi: 10.3866/PKU.WHXB19900104

研究论文 上一篇    下一篇

芬太尼类化合物中4-取代基作用的研究

陈常英;李玉林;连洪寿;陈冀胜   

  1. 中国人民解放军药物化学研究所,北京
  • 收稿日期:1988-03-28 修回日期:1988-12-14 发布日期:1990-02-15
  • 通讯作者: 陈常英

Studies on Action of 4-Substituent in Fentanyl Derivatives

Chen Chang-Ying;Li Yu-Lin;Lian Hong-Shou;Chen Ji-Sheng   

  1. Institute of Pharmaceutical Chemistry,PLA,Beijing
  • Received:1988-03-28 Revised:1988-12-14 Published:1990-02-15
  • Contact: Chen Chang-Ying

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。

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 showed that the cause of effect of 4-substituent on biological activity not that change of conformations but that electronic factors. The 4-non-polar-substituents have not con-tribution upon increase of activity. The 4-polar-substituents form new additional negative electronic region, which may be the main assistant site interacting with receptor, the additional negative electrostatic potential region may interact with receptor at a new site or the site in common with amide oxygen. It is no doubt that the additional negative electrostatic potential field generated by the 4-polar-substituent dramatically increases the analgesic activity of the fentanyl derivatives.