4-氨基哌啶类化合物的设计、合成及其对单胺递质再摄取的抑制活性  

Design,synthesis and monoamine reuptake inhibitors activities of 4-aminopiperidine derivatives

作　　者：郑永勇[1] 俞蕾平[2] 郭琳[2] 李建其[1] 

机构地区：[1]上海医药工业研究院,上海200040 [2]中国科学院上海药物研究所,上海201203

出　　处：《中国药物化学杂志》2010年第6期476-483,共8页Chinese Journal of Medicinal Chemistry

基　　金：国家自然科学基金项目(30772623);国家十一五"重大新药创制"项目(2009ZX09103-048)

摘　　要：目的设计合成4-氨基哌啶类化合物并研究其对中枢单胺递质（5-HT/NA/DA）的再摄取抑制活性。方法取代的4-氨基哌啶与氯代芳酮进行N-烷基化反应,经成盐制得目标产物Ⅰ1~Ⅰ9,再经硼氢化钠还原、成盐酸盐后制得目标产物Ⅰ10~Ⅰ17;经单胺递质再摄取抑制试验,对目标化合物的活性进行了初步测试。结果与结论共合成了17个未见文献报道的新化合物,经高分辨质谱及核磁共振氢谱确证结构。其中5个化合物对单胺递质再摄取具有一定的抑制活性。Aim To design and synthesize 4-aminopiperidine derivatives monoamine reuptake inhibitors.Methods The target compounds Ⅰ1-Ⅰ9 were prepared by N-alkylation of 4-aminopiperidine derivatives,and compounds Ⅰ10-Ⅰ17 were obtained by reduction of compounds Ⅰ1-Ⅰ9 with NaBH4.Results and conclusion Seventeen new target compounds were synthesized and their structures were confirmed by HR-MS and 1H-NMR.The results of preliminary pharmacological test showed that five of seventeen compounds possessed diverse monoamine reuptake inhibitors activities.

关 键 词：4-氨基哌啶 单胺递质再摄取抑制剂 合成 

分 类 号：R914[医药卫生—药物化学]