摘要
目的寻找具有Ⅲ/Ⅱ复合作用的新型抗心律失常药物。方法拼合1-苄基-1,2,3,4-四氢异喹啉与具有Ⅲ/Ⅱ复合作用的sotalol结构片段,设计合成1-苄基-2-(4′-甲磺酰基-1-羟基-苯乙基)-1,2,3,4-四氢异喹啉类化合物,通过离体豚鼠心肌标本不应期测定法对所合成的目标化合物进行筛选。结果合成了18个未见文献报道的新化合物(1a-1r)。体外结果表明化合物1d、1e、1i、1j具有较好的延长动作电位时程的作用。结论化合物1d、1e、1i、1j表现出Ⅲ类抗心律失常药物延长动作电位时程的特征,有关Ⅲ/Ⅱ复合作用的药理实验有待进行。
Aim To seek class Ⅲ antiarrhythmic agents with combinational inhibiting effect on potassium channel and β-receptor. Methods 1-Benzyl-2-（ 1-hydroxy-4＇-methylsulfonamidophenylethyl）-l, 2, 3, 4-tetrahydroisoquinolines 1a- 1r were designed and synthesized by incorporating 1-benzyl-1, 2, 3, 4-tetrahydroisoquinoline moiety into the pharmacophore of d, l-sotalol, and their activities were screened on left atrium of guinea pig by recording their prolonging functional refractory period （FRP） under electro-stimulus. Results In vitro bioactivity screening results indicated that compounds 1d, 1e, 1i and 1j had potential prolonging effect of FRP. Conclusion Compounds 1d, 1e, 1i and 1j displayed characters of class Ⅲ antiarrhythmic agents, and further comprehensive pharmacological experiments should be conducted to observe their combinational action.
出处
《中国药物化学杂志》
CAS
CSCD
2007年第2期65-71,共7页
Chinese Journal of Medicinal Chemistry
