光学活性甲苯喹哌的合成及其抗心律失常作用  

SYNTHESIS OF OPTICAL ACTIVE TOQUIPIDINES AND THEIR ANTIARRHYTHMIC EFFECTS

作　　者：周智善[1] 沈筱同[2] 屠传廉 林加宝 

机构地区：[1]上海医科大学药学院合成药物化学教研室 [2]上海医科大学药学院基础医学部药理教研室

出　　处：《中国药物化学杂志》1990年第1期21-25,共5页Chinese Journal of Medicinal Chemistry

基　　金：卫生部85-120-1号科研基金

摘　　要：(±)-1-对甲苯基-1,2,3,4-四氢异喹啉(4)经用二苯甲酰基-d-酒石酸拆分得(-)物体(8)和(+)物体(9),将(4),(8),(9)分别先后与氯乙酰氯及六氢吡啶反应,制得(±)、(-)和(+)-甲苯喹哌。后两者初步推定为S和R构型。三种甲苯喹哌经北草乌头碱致大鼠心律失常的治疗作用和毒性初步观察结果,右旋体的抗心律失常活性为左旋体的4.8倍,为消旋体的3.6倍,但其毒性分别为后二者的2.4和5.1倍。治疗指数仍为外消旋体较高。In order to obtain the optical isomers of Toquipidine, 1-p-methylphenyl-2-(α-piperidinoacetyl)-1,2,3,4-tetrahydroisoquinolide hydrochloride, for pharmacological evaluation, (+)-and (+)-toquipidines were prepared by optical resolution of racemic 1-p-methylphenyl-1,2,3,4-tetrahydroisoquinoline with dibenzoyl-d-tartaric acid, chloroacetylation and amination. Their configuration was inferred from the relationship between configuration of some tetrahydroisoquinoline analogues and their optical rotatins. The (-)-compound is a S-form and (+)-compound R-form. Their antiarrhythmic effects against aconitine arrhythmia in rats and acute toxicity were determined. The activity of (+)-form was 4.5 times that of (-)-form and 3.6 times that of (±)-form in antiarrhythmic effects, but 2.4 times and 5.1 times in toxicity respectively. The curative ratio of racemic toquipidine is better than those of others.

关 键 词：甲苯喹哌 四氢异喹啉衍生物 心律失常治疗药物 

分 类 号：R914[医药卫生—药物化学]