作用于神经系统药物:吡啶并[1,2-a]嘧啶酮系列化合物的合成

加锡果宁(Ⅰ)是中药野花椒的成分之一,具有较强的镇痛作用和中枢抑制作用。为寻找低毒高效的类似物,我们曾对其进行结构改造,设计合成了系列化合物并进行了药理试验。前文报道的是在母核芳环上引入不同取代基而不改变母核结构,本文进一步对不同母核的类似物进行了合成及药理研究。

SYNTHESIS OF PYRIDO [1,2-a] PYRIMIDINONE SERIES OF COMPOUMDS, POTENTIAL AGENTS ON THE NERVOUS SYSTEM

In an effort to modify the structure of edulinine so to seek compounds exhibiting higher potency toward inhibition of central nervous system, we designed and synthesized several analogous compounds: 2-methoxy-3-(3-methyl-2-butenyl)-4-oxo-4 H-pyrido [1,2-a] pyrimidine (IV), 3-methoxy-3-(3-methyl-2-butenyl)-2-oxo-2H-pyrido[1,2-a]pyrimidine (V), 2-methoxy-3-(2,3-dihydroxy-3-methyl-1-butyl)-4-oxo-4H-pyrido[1,2-a] pyrimidine (VI), and 4-methoxy-3-(2,3-dihydroxy-3-methyl-1-butyl)-2-oxo-2H-pyrido[1,2-a] pyrimidine (VII). Animal experiments revealed that compound (IV) has anticonvulsant activity, compounds (V) and (VI) have far lower activity than compound (IV).