中国药物化学杂志
中國藥物化學雜誌
중국약물화학잡지
Chinese Journal of Medicinal Chemistry
2007年
2期
65-71
,共7页
冉崇昭%吴泰志%王国平%谢美华%闵旸
冉崇昭%吳泰誌%王國平%謝美華%閔旸
염숭소%오태지%왕국평%사미화%민양
化合物制备%四氢异喹啉%索他洛尔%Ⅲ类抗心律失常药
化閤物製備%四氫異喹啉%索他洛爾%Ⅲ類抗心律失常藥
화합물제비%사경이규람%색타락이%Ⅲ류항심률실상약
compound preparation%tetrahyroisoquinoline%sotalol%class Ⅲ antiarrhythmic agent
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sotaol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.
目的 尋找具有Ⅲ/Ⅱ複閤作用的新型抗心律失常藥物.方法 拼閤1-芐基-1,2,3,4-四氫異喹啉與具有Ⅲ/Ⅱ複閤作用的sotaol結構片段,設計閤成1-芐基-2-(4'-甲磺酰基-1-羥基-苯乙基)-1,2,3,4-四氫異喹啉類化閤物,通過離體豚鼠心肌標本不應期測定法對所閤成的目標化閤物進行篩選.結果 閤成瞭18箇未見文獻報道的新化閤物(1a～1r).體外結果錶明化閤物1d、1e、1i、1j具有較好的延長動作電位時程的作用.結論 化閤物1d、1e、1i、1j錶現齣Ⅲ類抗心律失常藥物延長動作電位時程的特徵,有關Ⅲ/Ⅱ複閤作用的藥理實驗有待進行.
목적 심조구유Ⅲ/Ⅱ복합작용적신형항심률실상약물.방법 병합1-변기-1,2,3,4-사경이규람여구유Ⅲ/Ⅱ복합작용적sotaol결구편단,설계합성1-변기-2-(4'-갑광선기-1-간기-분을기)-1,2,3,4-사경이규람류화합물,통과리체돈서심기표본불응기측정법대소합성적목표화합물진행사선.결과 합성료18개미견문헌보도적신화합물(1a～1r).체외결과표명화합물1d、1e、1i、1j구유교호적연장동작전위시정적작용.결론 화합물1d、1e、1i、1j표현출Ⅲ류항심률실상약물연장동작전위시정적특정,유관Ⅲ/Ⅱ복합작용적약리실험유대진행.
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)-1, 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.
