Böttcher H, Barnickel G, Hausberg H H, Haase A F, Seyfried C A, Eiermann V
E. Merck Darmstadt, Preclinical Pharmaceutical Research and Central Analytical Laboratory, Germany.
J Med Chem. 1992 Oct 30;35(22):4020-6. doi: 10.1021/jm00100a006.
The synthesis and dopaminergic properties of a novel type of dopamine agonist is described. The number and kind of essential structural elements differ significantly from that of the rigid apomorphine-type dopamine agonists. Using standard molecular modeling techniques, a conformational model is developed proposing a U-shaped conformation which might be energetically preferred through aromatic pi-pi-interactions between both of the electron rich aromatic structural elements of this class of compounds. Superimposition of conformations of the lead compound 28 with apomorphine yields a novel model explaining the atypical structure-activity relationships found in this class of indolealkylamines.
描述了一种新型多巴胺激动剂的合成及其多巴胺能特性。其必需结构元件的数量和种类与刚性阿扑吗啡型多巴胺激动剂有显著差异。使用标准分子建模技术，构建了一个构象模型，该模型提出了一种U形构象，通过这类化合物的两个富电子芳香结构元件之间的芳香π-π相互作用，这种构象在能量上可能更有利。先导化合物28与阿扑吗啡的构象叠加产生了一个新模型，解释了这类吲哚烷基胺中发现的非典型构效关系。
