N-酰基-1-苄基四氢异喳啉衍生物的合成和GABA转运蛋白抑制作用

目的设计合成N-酰基-1-(3,4-二甲氧基)苄基-6,7-二甲氧基-1,2,3,4-四氢异喹啉类化合物,评价其抑制GABA转运蛋白对GABA的摄取作用.方法经核磁共振氢谱、质谱、高分辨质谱和红外光谱确证目标物的结构,并经体外GAT-1竞争抑制性结合试验进行活性筛选.结果与结论合成了4个目标化合物,初步活性试验表明,化合物1c和1d对GAT-1的抑制作用要大于阳性对照药(R)-3-哌啶甲酸,显示较强的GAT-1抑制作用.

Synthesis and GABA transporter inhibitory activities of N-acyl-1-benzyl tetrahydroisoquinoline derivatives

Aim To design and synthesize a series of new Nacyl-l-benzyl tetrahydroisoquinoline derivatives and evaluate their GABA transporter inhibitory activities in vitro.Method Four new compounds were synthesized and their structures were confirmed by()~1H-NMR,MS,HRMS and IR.The IC_(50) values of the synthetic compounds la-1d in vitro test for-GABA uptake inhibitors were determined using cultured cell lines expressing mouse GAT-1.Results and conclusion All the target compounds show definite GABA transporter inhibitory activities in vitro.Some of them,such as compounds 1c and 1d have more potent GABA transporter inhibitory activities than(R)-nipecotic acid.