α-胺基苄基膦酸酯的合成及其生物活性  

Synthesis and bioactivity of substituted α-aminobenzylphosphonate

作　　者：赵利枝[1] 杨日芳[1] 赵如胜[1] 张雁芳[1] 陈冬梅[1] 汪海[1] 

机构地区：[1]军事医学科学院毒物药物研究所,北京100850

出　　处：《药学学报》2006年第4期342-345,共4页Acta Pharmaceutica Sinica

基　　金：国家重点基础研究发展计划(国家973计划)资助项目(G199805112).

摘　　要：目的寻找具有内皮依赖性舒张血管活性的新结构胺基膦酸酯类化合物。方法运用一种新型的类M ann ich反应,以生物电子等排体原理设计合成了一系列α-胺基苄基膦酸酯类化合物,并运用离体大鼠血管环和离体豚鼠回肠收缩实验观察其舒张血管活性及其对M受体的激动作用。结果共合成了7个新的α-胺基苄基膦酸酯类目标化合物,其结构经IR,1H NMR和元素分析确定。初步离体血管环实验和离体豚鼠回肠收缩实验结果显示,化合物2a,2b和2 c有一定的舒张血管活性且不激活平滑肌M受体。结论在浓度为1×10-5mol.L-1时,化合物2b和2 c有较强的舒张血管活性,其舒张率分别为(67±21)%,(82±18)%,而且不激动M受体,其中,化合物2b有内皮依赖性的舒张血管反应。Aim To search for some substituted α-amino phosphonates as leading compounds with the vasodilator effects. Methods Target compounds were prepared from benzyl aldehyde, piperazine and diethyl phosphite using alcohol as solvent via Mannich-type reaction. In isolated rat aorta and in isolated guinea pig ileum, the vasodilator effects of compounds were investigated and evaluated whether they activated muscarine receptor. Results Seven compounds of substituted α-amino phosphonates have been synthesized and identified by IR, ^1H NMR and elemental analysis. Three of them, compound 2a, 2b and 2c have vasodilator activity and do not activate M receptor. Conclusion Two （2b and 2c） of them were found to have the notable vasodilator effect, and the rates of relaxing are （67 ±21 ）% and （82 ±18）% , separately. But they did not activate M receptors on ileum.

关 键 词：α-胺基膦酸酯 类Mannich反应 内皮细胞 舒张血管活性 M受体 

分 类 号：R916.41[医药卫生—药学]