Bøgesø K P, Arnt J, Lundmark M, Sundell S
J Med Chem. 1987 Jan;30(1):142-50. doi: 10.1021/jm00384a024.
Eight indolizidine and quinolizidine derivatives of 3-PPP were synthesized and tested for possible dopamine (DA) autoreceptor activity. The equatorial indolizidine derivative 19e had the profile of a selective autoreceptor agonist and was half as active as 3-PPP. However, resolution of the compound revealed that the 8R enantiomer was an unselective DA agonist with a profile similar to (+)-3-PPP, while the 8S enantiomer was a weak DA antagonist without any DA agonist activity. The unsaturated quinolizidine derivative 21 also had the profile of a DA antagonist while the axial quinolizidine derivative 18a had an amphetamine-like profile in 6-OHDA-lesioned rats. All other derivatives were inactive. The observed structure-activity relationships were in agreement with existing DA receptor models, although these models are not apparently detailed enough to explain why the 8S enantiomer of 19e is inactive as a DA agonist.
合成了8种3-PPP的中氮茚和喹嗪衍生物，并对其潜在的多巴胺（DA）自身受体活性进行了测试。赤道型中氮茚衍生物19e具有选择性自身受体激动剂的特征，活性为3-PPP的一半。然而，该化合物的拆分显示，8R对映体是一种非选择性DA激动剂，其特征与（+）-3-PPP相似，而8S对映体是一种弱DA拮抗剂，没有任何DA激动剂活性。不饱和喹嗪衍生物21也具有DA拮抗剂的特征，而轴向喹嗪衍生物18a在6-OHDA损伤的大鼠中具有类似苯丙胺的特征。所有其他衍生物均无活性。观察到的构效关系与现有的DA受体模型一致，尽管这些模型显然不够详细，无法解释为什么19e的8S对映体作为DA激动剂无活性。
