一氧化氮供体型抗高血压药物的研究Ⅰ.C-3位具有硝酸酯和呋咱氮氧化物取代结构的苯骈吡喃类化合物的合成及其降压活性  

Study on NO-Donating Antihypertensive AgentsⅠ. Synthesis and Antihypertensive Activity of C-3 Nitrate or Furoxan Substituted Benzopyrans

作　　者：许忻[1] 张奕华[1] 彭司勋[1] 季晖[2] 李永齐[2] 

机构地区：[1]中国药科大学新药研究中心 [2]中国药科大学药理学教研室,南京210009

出　　处：《中国药科大学学报》2005年第6期488-495,共8页Journal of China Pharmaceutical University

摘　　要：目的:研究C-3位一氧化氮(NO)供体取代的苯骈吡喃类化合物的合成及其降压活性,寻找活性强、不良反应小的新型抗高血压药。方法:以3,4位反式苯骈吡喃为基本骨架,在C-3位通过丁二酸连接硝酸酯和呋咱氮氧化物,合成了一系列衍生物;测定目标物对KCl引起的大鼠胸主动脉条收缩的抑制作用,选择活性化合物Ⅱ1测定其经口给药对自发性高血压大鼠(SHR)尾动脉收缩压(SAP)和舒张压(DAP)的影响;采用Griess法测定目标物体外NO释放量。结果与结论:合成了16个新化合物(Ⅰ1-6;Ⅱ1-10),结构经波谱确证。大部分目标物对大鼠胸主动脉条收缩具有不同程度的抑制作用,其中Ⅱ1的抑制率与阳性药吡那地尔(PIN)相当,对SHR尾动脉SAP和DAP的抑制幅度分别为15.2%和12.5%,降压持续时间长于PIN。Ⅱ1的NO释放量为0.9μg/mL,NO释放量与目标物降压活性的关系尚待进一步研究。AIM： To study the synthesis and antihypertensive activity of NO-donating benzopyran compounds and search for novel antihypertensive agents with better efficacy and less side-effects. METHODS： Sixteen novel compounds were synthesized by coupling of organic nitrate and furoxan with trans-3,4-benzopyran on the C-3 position through succinic acid. The inhibition of the target compounds on KCl-induced contraction of the aortic strips and the effects on systolic aortic pressure （SAP） and diastolic aortic pressure （DAP） of the spontaneously hypertensive rats （SHR） were measured. The amount of NO released in vitro of the compounds was also determined by Griess method. RESULTS AND CONCLUSION： The preliminary pharmacological testings showed that most of the target compounds inhibited the KCl-induced contraction to some extent. And among them, Ⅱ1 decreased SAP （15.2%） and DAP （12.5%） of the SHR with a longer duration than did control pinacidil. The amount of NO released by Ⅱ1 was 0.9μg/mL. The relationship between NO release and the antihypertensive effect of the target compounds remains to be investigated.

关 键 词：一氧化氮供体 硝酸酯 呋咱氮氧化物 苯骈吡喃 抗高血压 合成 

分 类 号：R914.5[医药卫生—药物化学] R962[医药卫生—药学]