Cappelli A, Donati A, Anzini M, Vomero S, De Benedetti P G, Menziani M C, Langer T
Dipartimento Farmaco Chimico Tecnologico, Università di Siena, Italy.
Bioorg Med Chem. 1996 Aug;4(8):1255-69. doi: 10.1016/0968-0896(96)00122-8.
The molecular structure and the dynamic behaviour of some potent 5-HT3 antagonists structurally related to quipazine have been investigated by NMR spectroscopy and by computational methods in order to gain insight into the structure-activity relationships at a molecular level. The role of the different dynamic behaviour of these compounds in the binding to 5-HT3 receptors is discussed. A model of ligand-receptor interaction has been developed on the basis of molecular orbital calculations and on the reference ligands quipazine, ondansetron and LY278584. The interaction model proposed herein rationalizes the observed agonist-antagonist shift between quipazine and investigated compounds with the assumption of different but overlapping binding domains for antagonists and agonists at the 5-HT3 receptor.
为了在分子水平上深入了解构效关系，通过核磁共振光谱法和计算方法研究了一些与喹哌嗪结构相关的强效5-HT3拮抗剂的分子结构和动态行为。讨论了这些化合物不同动态行为在与5-HT3受体结合中的作用。基于分子轨道计算以及参考配体喹哌嗪、昂丹司琼和LY278584，建立了配体-受体相互作用模型。本文提出的相互作用模型通过假设拮抗剂和激动剂在5-HT3受体上具有不同但重叠的结合域，解释了喹哌嗪与所研究化合物之间观察到的激动剂-拮抗剂转变。
