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

樟脑-1,2,4-三嗪的合成及其中枢神经兴奋活性

• 批准号: 02670961
• 负责人: NAGAI Shin-ichi
• 金额: $ 1.34万
• 依托单位: Nagoya City University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1990
• 资助国家: 日本
• 起止时间: 1990 至 1991
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-02670961/
• 关键词: Camphor-1, 2, 3-triazine; CNS stimulant activity; Structure activity relationship; Pharmacophore; 構造活性相関; カンファ-1,2,4ートリアジン; 主作用団; ヘテロ環縮合カンファ-1,2,4ートリアジン類; カンファー1,2,3ートリアジン; 中枢興奮作用; 活性コンホメ-ション; ヒドラジノカンファー1,2,4ートリアジン; ヘテロ環の構築

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.

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。从这些观察中可以得出结论，由N-N键组成的樟脑-1，2，4-三嗪的C-3取代基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基团取代会导致活性消失。

项目成果

Shinーichi Nagai: "Synthesis and Biological Activity of Fused Camphorー1,2,4ーtriazines" Heterocyclos. 31. (1991)

Shinichi Nagai：“融合樟脑-1,2,4-三嗪的合成和生物活性”Heterocyclos 31。（1991）

Shin-ichi NAGAI: "Synthesis and CNS stimulant activity of 5, 8-methano1, 2, 4-benzotriazines fused with tetrazole and 1, 2, 4-triazole." Chem. Pharm. Bull.40. (1992)

Shin-ichi NAGAI：“与四唑和 1, 2, 4-三唑稠合的 5, 8-methano1, 2, 4-苯并三嗪的合成和中枢神经系统刺激活性。”

Shin-ichi NAGAI: "Synthesis and CNS stimulant activity of 5, 8-methano1, 2, 4-benzotriazines fused with imidazole, thiodiazole and pyrimidine" Heterocycles. 33. (1992)

Shin-ichi NAGAI：“与咪唑、硫代二唑和嘧啶稠合的 5, 8-methano1, 2, 4-苯并三嗪的合成和中枢神经系统刺激活性”杂环。