N-酰基-1-苄基四氢异喹啉衍生物的合成和GABA转运蛋白抑制作用

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

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。

Aim To design and synthesize a series of new N-acyl-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 IC50 values of the synthetic compounds 1a- 1d in vitro test for[3H]-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 lc and ld have more potent GABA transporter inhibitory activities than（R ）-nipecotic acid.