【摘要】 目的寻找具有更强镇咳活性的化合物。方法以苯胺和二乙醇胺为原料,通过环合反应制得苯基哌嗪(2 ) ,2与环氧氯丙烷发生N 烷基化反应,所得产物和胺直接开环制得羟丙哌嗪衍生物;用“序贯法”测试目标化合物对小鼠的镇咳活性。结果与结论合成了15个未见报道的新化合物,并通过核磁共振氢谱、质谱确证结构;小鼠试验表明,所有新化合物均具有显著的镇咳效果,与阳性对照———左羟丙哌嗪(LD)的镇咳活性相当。更多还原

【Abstract】 Aim To search for novel potent compounds with antitussive activity for the treatment of respiratory system disease.Methods According to the mechanism of cough reflex,the role of c-fiber in the respiratory system and the principle of isosterism,a peripheral antitussive levodropropizine(LD)was regarded as a lead compound.Amino functional groups,as substituents at the 1-hydroxy group of the racemate of LD,were introduced into the structure of the molecule.A cyclization between aniline and diethanolamine form the ring of phenylpyperazine(2)directly.Compound 2 reacted with epoxy chloropropane to give compound 3 by N-alkylation.The title compound 4 was synthesized from compound 3 via ring-opening reaction directly.Their antitussive activities were studied on mice.Results and conclusion Fifteen compounds were synthesized and confirmed by ()~1H-NMR,MS.The results of preliminary pharmacological test show that all the novel compounds have antitussive activity comparable to that of the control LD.更多还原