摘要
目的寻找抗心律失常活性化合物。方法以抗心律失常药物sotalol(索他洛尔)为先导化合物,拼合具有抗室性心律失常活性的四氢异喹啉类化合物的药效基团,设计合成了9个N-2-(1-羟基-对甲磺酰基苯乙基)-1,2,3,4-四氢异喹啉类化合物,其结构经质谱和核磁共振波谱确证。并经离体豚鼠心肌功能不应期测定进行抗心律失常活性的筛选。结果合成9个未见文献报道的新化合物。化合物Ⅰ3和Ⅰ7具有一定抗Ⅲ类心律失常活性。结论可用某些基团取代的四氢异喹啉替代sotalol结构中的异丙胺基。
Aim To search more effective antiarrhythmic agents. Methods Taking sotalol, an effective antiarrhythmic drug, as lead compound, nine target compounds of N-2-hydroxyl-2-（4-methansulfonamidophenyl）- ethyl-1, 2, 3, 4-tetrahydroisoquinolines were designed and synthesized by incorporating tetrahydroisoquinoline pharmacophore. All of their structures were confirmed by MS and ^1H-NMR spectra, and their preliminary antiarrhythmic activities were recorded as changing of functional refractory period（FRP） of isolated Guinea pig left atrial myocardium under electrical stimulation. Results The screening results showed that compounds Ⅰ 3 and Ⅰ 7 exhibited potential antiarrihythmic activity. The effect of Ⅰ 7 was similar to that of sotalol at 3 × 10^-5 mol·L^-1. Conclusion The isopropylamine group in sotalol can be substituted by tetrahydroisoquinoline moiety.
出处
《中国药物化学杂志》
CAS
CSCD
2006年第3期140-143,共4页
Chinese Journal of Medicinal Chemistry
关键词
药物化学
化合物制备
化学合成
四氢异喹啉
索他洛尔
抗心律失常
medicinal chemistry
compound preparation
chemical synthesis
tetrahydroisoquinoline
sotalol
antiarrhythmia
