A New Synthesis Method and GABA Transporters Inhibitory Activities of Tiagabine and Its Analogues  

作　　者：ZHANG Jian-ge JIANG Chang-sheng ZHENG Jian-bin WEN Ren LIN Guo-qiang 

机构地区：[1]Department of Medicinal Chemistry, School of Pharmacy, Fudan University, Shanghai 200032, P. R. China [2]Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 201203, P. R. China

出　　处：《Chemical Research in Chinese Universities》2006年第3期351-355,共5页高等学校化学研究（英文版）

基　　金：SupportedbytheScienceandTechnologyCommissionofShanghaiMunicipality(No.03DZ19201).

摘　　要：A new synthetic method and GABA transporter inhibitory activities of Tiagabine and its analogues are described. The key intermediates 4-tosyl-1,1-diaryl/heteroaryl-l-butene 10a-10e were synthesized by Wittig reaction, and followed by N-alkylation with （R）-3-piperidinecarboxylate. The resulting N-diheterocyclylalkenylpiperidine-3-carboxylic acid ester 11a-11e were saponified and then acidified to.get the target compounds 1a-1e. The preliminary bioassays show that compound 1a-1e exhibited excellent inhibition of [ 3H ]-GABA uptake in vitro of culture ceils.A new synthetic method and GABA transporter inhibitory activities of Tiagabine and its analogues are described. The key intermediates 4-tosyl-1,1-diaryl/heteroaryl-l-butene 10a-10e were synthesized by Wittig reaction, and followed by N-alkylation with （R）-3-piperidinecarboxylate. The resulting N-diheterocyclylalkenylpiperidine-3-carboxylic acid ester 11a-11e were saponified and then acidified to.get the target compounds 1a-1e. The preliminary bioassays show that compound 1a-1e exhibited excellent inhibition of [ 3H ]-GABA uptake in vitro of culture ceils.

关 键 词：Tiagabine ANALOGUE SYNTHESIS GABA transporter inhibitor 

分 类 号：O623.736[理学—有机化学]