血小板活化因子受体拮抗剂——芳氨酮类化合物的合成及其抗炎活性

Synthesis and antiinflammation activity of aromatic aminoketone compounds, a new type of PAF-receptor antagonist

摘要: 以取代亚苄基丙酮和二级胺盐酸盐经Mannich反应合成了一系列具有抗炎活性的芳氨酮类化合物，其结构经¹H NMR、MS、元素分析或HRMS确证。同时测定了所合成化合物对血小板活化因子(PAF)引起的大鼠胸腔多形核白细胞β-葡糖苷酸酶释放的抑制作用，初步药理实验结果表明，大部分芳氨酮类(MA)化合物对PAF引起的大鼠胸腔多形核白细胞β-葡糖苷酸酶的释放有明显的抑制作用，其中化合物MA12、MA13、MA18、MA21和MA33的抑制活性较强。提示化合物可通过抑制β-葡糖苷酸酶释放发挥抗炎作用，可能是潜在的PAF受体拮抗剂。

Abstract: A series of aromatic aminoketones were synthesized by Mannich reaction. Structures of these compounds were confirmed by ¹H NMR, MS and HRMS or element analysis. Pharmacological screening showed that most target compounds inhibited the release of β-glucuronidase in polymorphonuclear leucocytes by PAF (platelet activating factor) and compounds MA12, MA13, MA18, MA21 and MA33 were more active. The study suggests that target compounds are potential PAF receptor antagonists and their anti-inflammatory activities are due to the inhibition of release of lysosomal enzyme.