新型哒嗪酮衍生物的合成及其对血小板聚集的抑制作用
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摘要
目的合成新的含有胺基的哒嗪酮类化合物,并研究其对此类化合物抗血小板聚集活性的影响。方法设计合成未见报道的目标化合物9个,所有化合物均经过H-NMR谱等确证;参考文献方法进行体外药理实验。结果发现所有化合物都具有抗血小板凝集的活性,其中化合物9c,9e和9i的抗血小板凝集活性明显优于对照化合物MCI-154和CCI-17910。结论引入不同的取代胺基,对化合物抑制血小板聚集的活性有影响。
Objective To study the antiplatelet aggregative activity of 6-(4-substitued acetamino-phenyl 4,5-dihydro-3(2H)-pyridazinones with different amino group.Methods Nine target compounds were designed and synthesized.All of them were confirmed by ' H-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 antiplatelet aggregative activity to a certain extent.Compounds 9c,9e and 9i were better than MCI-154 and CCI-17910 in vitro.Conclusion Inletting different substituted amino groups could enhance the antiplatelet aggregation activity of the compounds.
Objective To study the antiplatelet aggregative activity of 6-(4-substitued acetamino-phenyl 4,5-dihydro-3(2H)-pyridazinones with different amino group.Methods Nine target compounds were designed and synthesized.All of them were confirmed by ' H-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 antiplatelet aggregative activity to a certain extent.Compounds 9c,9e and 9i were better than MCI-154 and CCI-17910 in vitro.Conclusion Inletting different substituted amino groups could enhance the antiplatelet aggregation activity of the compounds.
引文
[1]Bristol JA,Sircar L,Moos WH,el al.Cardiotonic agents 1.4,5-dihydro-6-[4-(lH-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]Yang GM,Liu LM,Xu J.Effects of MlC-154 on vascular reactivity and its mechanisms after hemorrhggic shock in rats[J].J Cardiovasc Pharmacol,2006,47(6):751.
[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]王曙东,陈兴东.赵庆杰,等.哒嗪酮类新衍生物的合成及其对血小板聚集的抑制作用[J].药学实践杂志,2011,29(5):362.
[5]章杰兵.柴晓云,俞世冲.等.哒嚎酮类新衍生物的合成及其对血小板聚集的抑制作用[J].第二军医大学学报.2009,30(7):821.
[6]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.
[7]Bom GVR.Aggregation of bioodplatelets by adenosine diphosphate and its reversal[J].Nature,1962,194(4832):927.
[2]Yang GM,Liu LM,Xu J.Effects of MlC-154 on vascular reactivity and its mechanisms after hemorrhggic shock in rats[J].J Cardiovasc Pharmacol,2006,47(6):751.
[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]王曙东,陈兴东.赵庆杰,等.哒嗪酮类新衍生物的合成及其对血小板聚集的抑制作用[J].药学实践杂志,2011,29(5):362.
[5]章杰兵.柴晓云,俞世冲.等.哒嚎酮类新衍生物的合成及其对血小板聚集的抑制作用[J].第二军医大学学报.2009,30(7):821.
[6]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.
[7]Bom GVR.Aggregation of bioodplatelets by adenosine diphosphate and its reversal[J].Nature,1962,194(4832):927.