Duax W L, Smith G D, Griffin J F, Portoghese P S
Science. 1983 Apr 22;220(4595):417-8. doi: 10.1126/science.6301007.
The inactive methadone analog threo-5-methylmethadone has a solid-state conformation in which the nitrogen is antiperiplanar to the tertiary carbon C(4). Since threo-5-methylmethadone exhibits no opioid agonism either in vivo or in vitro, methadone analogs probably do not have this conformation when bound to an opioid receptor. The potent agonist (-)-erythro-5-methylmethadone has a solid-state conformation in which the nitrogen atom is rotated back toward the phenyl rings on the quarternary carbon, suggesting that this unusual conformation is the active one.
无活性的美沙酮类似物苏式-5-甲基美沙酮具有一种固态构象，其中氮原子与叔碳C(4)呈反式共平面。由于苏式-5-甲基美沙酮在体内或体外均无阿片样激动作用，因此美沙酮类似物与阿片受体结合时可能不具有这种构象。强效激动剂(-)-赤式-5-甲基美沙酮具有一种固态构象，其中氮原子朝着季碳上的苯环向后旋转，这表明这种不寻常的构象是活性构象。
