一氧化氮供体型雷诺嗪衍生物的合成及体外一氧化氮释放活性测定

目的 合成一氧化氮(NO)供体型雷诺嗪衍生物,检测其体外NO的释放能力,寻找新型抗心绞痛药.方法 以中间体2-(4-(2-羟基-3-(2-甲氧基苯氧基)-丙基)-1-哌嗪)乙酸(A)为基本骨架,根据药物设计的拼合原理将呋咱氮氧化物和硝酸酯与其偶联,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(Ⅰ1～Ⅰ7,Ⅱ),其中7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.

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

Objective To synthesize a serial of nitric oxide-releasing Ranolazine derivatives,and determine their NO-relea-sing ability in vitro. Methods NO-releasing Ranolazine derivatives were synthesized by coupling 2-(4-(2-hydroxyl-3-(2-me-thoxyPhenoxy)- propyl)-l- piperazine) acetic acid (A) with furoxan or nitrate ester moieties through the carboxyl group of C. Results Eight new NO-releasing Ranolazine derivatives were synthesized,and their NO-releasing activity in vitro was determined. Conclusion The target compounds were confirmed by ~1H-NMR. Furoxan-type compounds can release NO effectively in vitro.