1-取代芳基-4-取代芳氧基丙基哌嗪的设计合成和生物活性研究  

Design,synthesis and biological activity of 1-substituted aryl-4-substituted aryloxypropyl piperazine

作　　者：季红[1] 李国荣[1] 吴丽阳[1] 蔡江红[1] 刘玉荣[2] 

机构地区：[1]广州医科大学药学院,广东广州510182 [2]广州医科大学基础学院,广东广州510182

出　　处：《化学研究与应用》2017年第4期499-504,共6页Chemical Research and Application

基　　金：广东省科技计划项目(2015A020211039)资助;广州市珠江科技新星专项项目(2011J2200011)资助;广州市教育局科研项目(10A257)资助

摘　　要：以4-取代苯酚或2-氟-3-羟基吡啶为原料,在碱性条件下与对甲苯磺酸缩水甘油酯通过亲核取代反应制备3-取代芳氧基-1,2-环氧丙烷(2)。取代芳胺与二氯二乙基胺盐酸盐反应生成1-取代芳基哌嗪(3)。2与3通过环氧开环反应得到1-取代芳基-4-取代芳氧基丙基哌嗪(4)。采用NMR和MS谱确定了合成化合物的结构。通过大鼠离体肛尾肌张力实验对合成化合物进行了α_1-受体拮抗活性研究,发现这些化合物的pA_2>6,显示较好的α_1-受体拮抗活性。化合物(4a)的pA_2=8.39±0.31,活性最突出。3-Substituted aryloxy-1 ,2-epoxypropane（2 ） was obtained through substitution reaction of starting material 4-substituted phenol or 2-fluoro-3-hydroxypyridine with glycidyl tosylate in alkaline condition. Ring opening reaction of 2 with 1 -substituted arylpiperazine（3 ） which was prepared by the reaction of substituted aromatic amine and 2 ,2 ＇-dichlorodiethylamine h y drochloride of-fered 1-substituted aryW-substituted aryloxypropyl piperazine（4）. The structure of the target compounds were characterized by their NMR and MS spectra. Their antagonistic activity against a l -receptor was studied in vitro by the response test of rat anococcygeus muscle to the synthesized compounds. All the compounds showed potent antagonistic activity against -receptor（ pA 2 〉6 ） , and com - pound（ 5a） inhibited the best potency（ pA 2 = 8 . 39±0. 3 1 ） .

关 键 词：哌嗪 设计与合成 α1-受体拮抗活性 

分 类 号：O626[理学—有机化学]