4-色满酮芳环Mannich碱类化合物的合成及其抗血小板聚集活性研究

4-色满酮类化合物和色酮类化合物具有广泛的生物活性。笔者曾发现4-色满酮3位Mannich碱类化合物具有显著的抗血小板聚集活性,为了考察在4-色满酮的3-位Mannich碱类化合物中3-位胺甲基侧链是否为加强活性的必需基团,为确定其药效构象提供信息,笔者设计合成了4种4-色满酮芳环Mannich碱类化合物,同时又合成了3种色酮芳环Mannich碱类化合物。所合成的目标化合物均未见文献报道,其组成和结构经红外光谱、质谱和核磁共振氢谱确认。采用Born's比浊法对目标化合物进行了抗血小板聚集活性的体外筛选。实验结果表明,目标化合物对ADP和胶原诱导的家兔血小板聚集均具有显著的体外抑制活性。

Synthesis and Anti-platelet Aggregative Activity of the Mannich Bases of 4-Chromanones and 4-Chromones

4-Chromanones and chromones are known to exhibit a wide range of biological activities.Mannich bases at 3-position of 4-chromanones synthesized in our laboratory exhibit the significant anti-platelet aggregative activity.On the base of our previous work,the mannich bases at aromatic ring of 4-chromanones and chromones which were designed as the candidates of platelet aggregative inhibitors were synthesized as shown,the seven target compounds which were not reported in the literature were synthesized and characterized by 1H NMR,IR,LC-MS and GC-MS.The anti-platelet aggregative activity of the target compounds was tested using Born's method.According to screening results,some of the target compounds such as 7-hydroxy-8-(4-morpholinomethyl)-4-chromanone and 7-hydroxy-2,8-di(4-morpholinomethyl)chromone showed potent inhibitory activity against rabbit platelet aggregation induced by ADP in vitro,some of the target compounds such as 7-hydroxy-2,8-di(4-morpholinomethyl)chromone showed potent inhibitory activity against rabbit platelet aggregation induced by collagen in vitro.