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  

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

作　　者：姜鸽[1] 郑晋鄂[2] 赵朝阳[2] 张静[2] 瞿小兰[2] 洪亮[2] 杨畅[2] 丁楠[2] 项光亚[2] 

机构地区：[1]华中科技大学同济医学院附属同济医院药剂科,武汉430030 [2]华中科技大学同济医学院药学院,武汉430030

出　　处：《华中科技大学学报（医学版）》2009年第5期664-668,共5页Acta Medicinae Universitatis Scientiae et Technologiae Huazhong

摘　　要：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。Objective To synthesize a serial of nitric oxide-releasing Ranolazine derivatives,and determine their NO-releasing ability in vitro.Methods NO-releasing Ranolazine derivatives were synthesized by coupling 2-（4-（2-hydroxyl-3-（2-methoxyPhenoxy）-propyl）-1-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 by1H-NMR.Furoxan-type compounds can release NO effectively in vitro.

关 键 词：抗心绞痛药 雷诺嗪 一氧化氮供体 合成 NO体外释放 

分 类 号：R916[医药卫生—药学]