苯并吡喃类C-4位一氧化氮供体衍生物的合成及降压活性  

Synthesis and anti-hypertensive activity of C-4 substituted NO-donating benzopyran derivatives

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,江苏南京210009 [2]中国药科大学药理教研室,江苏南京210009

出　　处：《中国药物化学杂志》2006年第1期15-19,共5页Chinese Journal of Medicinal Chemistry

摘　　要：目的 研究C-4位取代的一氧化氮（NO）供体型苯并吡喃类衍生物的合成及其降压活性，寻找新型抗高血压药。方法 以3、4位反式苯并吡喃为基本骨架，在G4位通过丁二酸连接硝酸酯和呋咱氮氧化物。合成一系列衍生物；测定目标物对KCl引起的大鼠胸主动脉条收缩的抑制作用；采用Griess法测定体外NO释放量。选择活性化合物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。结果与结论 合成了10个新化合物（Ⅲ1～Ⅲ10），结构经波谱和元素分析确证。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Ⅲ9的抑制率及降压持续时间均与阳性对照药吡那地尔（PIN）相当，对SHR尾动脉SAP和DAP的抑制幅度分别为22．1％和23．8％，体外NO释放量为0．9mg·L^-1。Aim To study the synthesis and anti-hypertensive activity of NO-donating benzopyran compounds and search for novel anti-hypertensive agents with high activity and less side-effects. Method Ten novel compounds Ⅲ1～Ⅲ10 were synthesized by coupling of organic nitrate and furoxan with trans-3, 4-henzopyran on the C-4 position through succinic acid. Their structures were confirmed by spectral data and elemental analysis. 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 detected. The amount of NO released in vitro of the compounds was also determined by Griess method. Result and conclusion The preliminary pharmacological tests showed that most of the target compounds inhibited the KCl-induced contraction to a certain extented. Among them Ⅲ 9 decreased SAP （22.1% ）and DAP（23.8 % ） of the SHR with the same duration as control pinacldil. The amount of NO released by Ⅲ is 0.9mg·L^-1.

关 键 词：药物化学 化合物制备 化学合成 一氧化氮供体 呋咱氮氧化物 苯并吡喃 抗高血压药物 

分 类 号：R914.5[医药卫生—药物化学]