Synthesis and CNS stimulant Activity of Camphor-1, 2, 4-triazines

为了阐明樟脑-1，2，3-三嗪及其相关化合物的结构与中枢神经系统兴奋活性的关系，以3-氨基或3-肼基樟脑-1，2，4-三嗪为结构单元，合成了一系列樟脑-1，2，4-三嗪与咪唑、1，2，4-三唑、噻二唑、咪唑啉、咪唑啉使用小鼠评价所得化合物的CNS刺激活性。其中3-肼基樟脑-1，2，4-三嗪的活性最强，樟脑-1，2，4-三嗪与四唑和1，2，4-三唑的稠合物的活性最强。从这些观察结果可以得出结论，樟脑-1，2，4-三嗪的C-3取代基由N-N键组成，应该是中枢神经系统刺激活性的基本药效团，因为N-N基团被N-C基团取代导致活性消失。

In order to clarify the relationship between structure and central nervous system(CNS)stimulant activity of camphor-1, 2, 3-triazine and related compounds, the isomeric 3-amino- or 3-hydrazino-camphor-1, 2, 4triazine was employed as building blocks for the synthesis of a series of camphor-1, 2, 4-triazines fused with imidazole, 1, 2, 4-triazole, thiodiazole, tetrazole-and pyrimidine.The CNS stimulant activity of the obtained compounds was evaluated using mice. Among the tested compounds, 3-hydrazino-camphor-1, 2, 4-triazine showed the most potent activity and camphor-1, 2, 4-triazines fused with tetrazole and 1, 2, 4-triazole were potent. From these observations, it was concluded that the C-3 substituent of camphor-1, 2, 4-triazine consisted of a N-N bonding should be the essential pharmacophore for the CNS stimulant activity, because the replacement of a N-N group by a N-C group resulted in disappearance of the activity.