一氧化氮供体型二氢吡啶类衍生物的合成及体外NO释放活性测定

Synthesis of NO-releasing Dihydropyridine Derivatives and Determination of Their NO-releasing Activities in vitro

目的合成一氧化氮供体型二氢吡啶类衍生物,检测其体外NO的释放能力,寻找新型抗高血压药。方法以中间体5-甲氧基羰基-2,6-二甲基-4-(3-硝基苯)-1,4-二氢吡啶-3-甲酸(M)为基本骨架,利用C-3位羧基与硝酸酯和呋咱氮氧化物结构偶联,合成系列目标化合物;采用Griess法测定目标化合物的NO体外释放量。结果合成了8个新化合物(Ⅰa～Ⅰf,Ⅱa～Ⅱb),其中6个呋咱氮氧化物类衍生物在体外具有良好的NO释放能力。结论所有化合物的结构均经1H-NMR确证,呋咱环型化合物在体外能有效释放NO。

Objective To design and synthesize a series of nitric oxide-releasing dihydropyridine derivatives,and to study their NO-releasing ability in vitro.Methods NO-releasing dihydropyridine derivatives were synthesized by coupling 5-（methoxy-carbonyl）-2,6-dimethyl-4-（3-nitrophenyl）-1,4-dihydropyridine-3-carboxylic acid （M） with furoxan or nitrate ester moieties through the carboxyl group of M.Results Eight new NO-releasing dihydropyridine derivatives were synthesized,and their NO-releasing activity was determined in vitro.Conclusion The target compounds were confirmed by 1H-NMR.Furoxan-type compounds can release NO effectively in vitro.