哒嗪酮类新衍生物的合成及其对血小板聚集的抑制作用
Synthesis and platelet aggregation inhibition activity of new derivatives of pyridazinone
-
摘要: 目的 研究引入取代仲胺类基团对6-(4-取代乙酰氨基苯基)-5-甲基-4, 5-二氢-3(2H)-哒嗪酮类化合物抗血小板凝集活性的影响。 方法 设计合成未见报道的目标化合物 10 个,所有化合物均经过1H-NMR谱等确证;参考文献方法进行体外药理实验。 结果 所有化合物都具有抗血小板凝集的活性,其中化合物 9c,9f 和 9j 的抗血小板凝集活性明显优于对照药MCI-154和CCI-17910。 结论 取代仲胺基团的空间位阻和亲水性对化合物抗血小板凝集的活性有影响。Abstract: Objective To study the antiplatelet aggregative activity of 6-(4-substitued acetamino-phenyl 4, 5-dihydro-3(2H)-pyridazinones with different substituted secondary amines. Methods Ten target compounds were designed and synthesized.All of them were confirmed by 1H-NMR spectra. Born method was applied for preliminary pharmacological test in vitro. Results All of the target compounds were not reported.The results of preliminary pharmacological test showed that all the target compounds exhibited potent anti-platelet aggregative activity to a certain extent.Compounds 9c, 9f and 9j were better than MCI-154 and CCI-17910 in vitro. Conclution The steric hindrance and hydrophilicity of different substituted secondary amines impact the anti-platelete aggative activity.
-
Key words:
- synthesis /
- pyridaziones /
- platelet aggregation in vitro /
-
[1] Bristol JA,Sircar L,Moos WH,et al.Cardiotonic agents. 1. 4, 5-Dihydro-6-[4-(1H-imidazol-1-yl)phenyl]-3(2H)-pyridazinones: novel positive inotropic agents for the treatment of congestive heart failure[J]. J Med Chem, 1984, 27(9): 1099. [2] 蒋 勤, 孙常晟.6-(4-取代苯基)-4,5-二氢-3(2H)-哒嗪酮类化合物的合成及其抑制血小板的作用[J]. 药学学报,1990,25(8):598. [3] Mikashima H,Nakao T,Goto K.Y-590 (A new pyridazinone derivative), a potent anti-thrombotic agent-I. Effect on platelet function[J]. Thromb Res, 1983,31(4): 599. [4] 王恩思,沈家聪.新型强心药匹莫苯的合成[J].中国药物化学杂志,1997,7(3):185. [5] Bom GVR.Aggregation of bloodplatelets by adenosine diphosphate and its reversal[J].Nature,1962,194(4832):927. -
点击查看大图
计量
- 文章访问数: 3174
- HTML全文浏览量: 276
- PDF下载量: 366
- 被引次数: 0
下载:
