N-取代苄基氟哌啶醇氯化物的合成及扩血管活性

Synthesis and vasodilative activities of N-substituted benzyl haloperidol chlorides

目的:合成N-取代苄基氟哌啶醇氯化物及其还原物并研究它们的扩血管活性。方法:氟哌啶醇、氢化氟哌啶醇在回流的情况下分别与取代氯苄反应依次得到N-苄基氟哌啶醇氯化物和N-苄基氢化氟哌啶醇氯化物;并测定其对KCl诱导的大鼠胸主动脉条收缩抑制作用。结果:合成了11个新化合物(IF_8～F_(13),ⅡFB_8～FB_(11),FB_(13))。离体扩血管活性实验表明,多数目标化合物表现为不同程度地阻滞KCl所致鼠胸主动脉条收缩血管的活性。结论:初步构效关系表明,N-取代苄基氟哌啶醇氯化物中苄基苯环上取代基的电性效应和取代位置可能为影响此类化合物扩血管活性的重要因素。氟哌啶醇母体上羰基被还原为羟基一般对其扩血管活性影响不大。

Objective:To evaluate the vasodilative effects of the synthetic N-substituted benzyl haloperidol chlorides and their hydrides. Methods: Haloperidol and hydrohaloperidol were reacted with substituted benzyl chlorides, respectively, to obtain 11 target products (6 N-substituted benzyl haloperidol chlorides and 5 N-substituted benzyl hydrohaloperidol chlorides). The vasodilative effects of the target products on spiral strips of isolated rat aorta in vitro were bioassayed. Results:Most of the target products moderately antagonized the contraction of the spiral strips of isolated rat aorta. Conclusion: The preliminary data suggested that the electron orientation and position of substitution in the aromatic group of N-benzyl haloperidol chlorides might play major roles in the vasodilative activities of the target products. The vasodilative activities were retained when the carbonyl group in haloperidol was reduced to the hydroxyl group.