论文部分内容阅读
本文用X光衍射结晶学,计算机辅助构象分析和分子图形学方法,对芬太尼类μ型阿片受体激动剂中七个典型代表物进行了研究。结果表明,芬太尼类化合物哌啶环4位丙酰苯胺基位置与生物活性有关。4-取代和顺式3-甲基芬太尼类化合物的晶体结构是一个能量较为合理的体系,在该体系下的构象有可能是生物活性构象,即哌啶环1-位苯乙基为伸展构象,哌啶环4-位扭角τ_4(C_(11)—C_(12)—N_(15)—C_(16))为100°左右时有利于与受体相互作用。并在构象分析和分子图形拟合的基础上,提出了芬太尼类化合物与阿片受体之间相互作用的结构要求。
In this paper, seven representative representatives of fentanyl μ-type opioid receptor agonists were studied by X-ray diffraction crystallography, computer-assisted conformational analysis and molecular graphic method. The results showed that the position of 4-position propionanilide of piperidine ring of fentanyl was related to biological activity. The crystal structure of 4-substituted and cis-3-methylfentanyl compounds is a more energy-efficient system. The conformation in this system may be the biologically active conformation, that is, the 1-position phenethyl group of piperidine ring is stretched Conformation and the 4-position torsion angle τ_4 (C_ (11) -C_ (12) -N_ (15) -C_ (16)) of piperidine ring is about 100 °. On the basis of conformational analysis and molecular graph fitting, the structural requirements of the interaction between fentanyl compounds and opioid receptors were proposed.