N-取代苄基氟哌啶醇氯化物及其还原物的合成与扩张血管活性  

Synthesis of N-substituted benzyl haloperidol chlorides and their vasodilating activities

作　　者：郑锦鸿[1] 王锦芝[1] 盘鹰[1] 石刚刚[2] 

机构地区：[1]汕头大学医学院化学教研室,广东汕头515041 [2]汕头大学医学院药理教研室,广东汕头515041

出　　处：《广东药学院学报》2004年第5期453-457,共5页Academic Journal of Guangdong College of Pharmacy

基　　金：20 0 1年度教育部留学回国人员科研启动基金课题 ;2 0 0 2年度广东省教育省"千百十工程"优秀人才培养基金;2 0 0 3年度广东省自然科学基金 (0 346 14 )项目

摘　　要：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张血管活性。方法以氟哌啶醇为原料 ,通过与取代氯苄化合物在回流下反应得到N 取代苄基氟哌啶醇氯化物 ;用氢化硼钠将氟哌啶醇还原为氢化氟哌啶醇 ,再与取代氯苄化合物在回流下反应得到N 取代苄基氢化氟哌啶醇氯化物 ;以兔胸主动脉螺旋条生物测定法研究其抑制血管收缩的活性。结果合成了 6个N 取代苄基氟哌啶醇氯化物F8-13 和 5个N 取代苄基氢化氟哌啶醇氯化物FB8-11,FB13 ;初步生物活性实验结果表明 ,F8-13 表现出不同程度的拮抗KCl所致兔胸主动脉螺旋条收缩血管活性 ,其中化合物F11的血管收缩抑制活性最强 ;但FB8-11,FB13 的活性均较低。结论化合物F11扩张血管活性强于先导化合物 ,初步构效关系表明 ,NObjective To study the synthesis of N-substituted benzyl haloperidol chlorides, N-substituted benzyl hydrohaloperidol chlorides and their vasodilating activities. Methods Haloperidol was reacted with different substituted benzyl chloride in reflux condition to synthesize the title compounds F 8-13. Haloperidol was reacted with sodium borohydride to form hydrohaloperidol, then reacted with different substituted benzyl chloride in reflux condition to synthesize the FB 8-11,FB 13. Using bioassay of spiral strips of isolated rabbit aorta, the vasodilating activities of these compounds were tested. Results 6 N-substituted benzyl haloperidol chlorides and 5 N-substituted benzyl hydrohaloperidol chlorides were synthesized. All of the 6 N-substituted benzyl haloperidol chlorides partially inhibited the KCl-induced contractions on spiral strips of isolated rabbit aorta. Compound F 11 indicated stronger and potential effect. However N-substituted benzyl hydrohaloperidol chlorides show lower vasodilating activities. Conclusion F 11 demonstrated superior cardiovascular activity to the lead compound. Primary structure-activity relationship indicated that electrical property and site of substitute on benzyl affects the inhibition of contraction on spiral strips of isolated rabbit aorta.

关 键 词：N-取代苄基氟哌啶醇氯化物 合成 扩血管活性 构效关系 

分 类 号：R914[医药卫生—药物化学] R96[医药卫生—药学]