O'Boyle K M, Waddington J L
Eur J Pharmacol. 1985 Sep 24;115(2-3):291-5. doi: 10.1016/0014-2999(85)90702-2.
A series of 1-phenyl-1H-3 benzazepine analogues of the D-1 agonist SK&F 38393 and of the D-1 antagonist SCH 23390 were compared for their relative abilities to displace the binding of [3H]piflutixol and [3H]spiperone to striatal D-1 and D-2 receptors respectively. The benzazepine analogues varied in substitutions at the 3- and 7-positions which distinguish SK & 38393 from SCH 23390. Substitutions at these positions critically influenced affinity for D-1 receptors over a 2000-fold range but influenced affinity for D-2 receptors over only a 30-fold range. 7-Substituents prominently increased affinity and selectivity for D-1 receptors with a rank order of Br = Cl much greater than CH3 greater than H greater than OH. 3-Methylation had a less marked and less selective action to increase affinity for D-1 receptors. Such structural relationships may aid the definition of the topography of brain D-1 receptors and the development of improved selective agents.
对一系列1-苯基-1H-3-苯并氮杂卓类似物进行了比较，这些类似物分别是D-1激动剂SK&F 38393和D-1拮抗剂SCH 23390的类似物，比较它们置换[3H]匹氟噻醇和[3H]螺哌隆与纹状体D-1和D-2受体结合的相对能力。苯并氮杂卓类似物在3位和7位的取代基有所不同，正是这些取代基区分了SK&38393和SCH 23390。这些位置的取代在超过2000倍的范围内对D-1受体的亲和力有至关重要的影响，但对D-2受体亲和力的影响范围仅为30倍。7位取代基显著增加了对D-1受体的亲和力和选择性，其顺序为Br = Cl远大于CH3大于H大于OH。3位甲基化对增加D-1受体亲和力的作用不太显著且选择性较低。这种结构关系可能有助于明确脑D-1受体的拓扑结构以及开发改进的选择性药物。
