羟丙哌嗪衍生物的合成及其镇咳活性

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.

Study on synthesis and antitussive activity of dropropizine derivatives

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.