吡唑并嘧啶类化合物的合成及其催眠作用的研究

目的设计并合成吡唑并嘧啶类化合物,并对其进行催眠作用研究。方法以乙酮类衍生物和N,N-二甲基甲酰胺二甲基缩醛为起始原料,再与3-氨基-4-氰基吡唑反应制备一系列吡唑并嘧啶类化合物;分别对阈下剂量戊巴比妥钠所致小鼠的催眠作用和阈上剂量戊巴比妥钠所致小鼠的催眠作用进行研究。结果设计并合成了7个目标化合物,其结构经~1H-NMR和ESI-MS确证。阈下剂量戊巴比妥钠所致小鼠的催眠作用研究表明化合物AL-5、AL-7有一定的协同戊巴比妥钠的催眠作用(P0.05),化合物AL-1、AL-3具有明显的催眠作用(P0.01)。阈上剂量戊巴比妥钠所致小鼠的催眠作用研究表明AL-1、AL-3、AL-5和AL-7组的睡眠持续时间均显著延长(P0.01、0.05),表明这些化合物有镇静催眠的效果。结论改进了吡唑并嘧啶类化合物的合成工艺,操作简单、成本低、产率较高;通过小鼠的行为学观察法对化合物的药效做了初步的评价,为今后的合成研究提供了方向。

Synthesis of pyrazolopyrimidine derivatives and their hypnotic activities

Objective To design and synthesize pyrazolopyrimidine derivatives, and to study their hypnotic activities. Methods Ethyl ketone derivatives and N, N-dimethylformamide dimethyl acetal were used as the starting material, and reacted with 3-aminopyrazole-4-carbonitrile to synthesize the target compounds. The hypnotic activities of subliminal dose and threshold dose of pentobarbital sodium in mice were studied. Results Seven targeted compounds were designed and synthesized, and their chemical structures were confirmed by ¹H-NMR and ESI-MS. The study on hypnotic activities of subliminal dose of pentobarbital sodium in mice showed that compounds AL-5 and AL-7 had cooperated with the hypnotic effect of pentobarbital sodium (P < 0.05). And compounds AL-1 and AL-3 had the significant hypnotic activities (P < 0.01). The study on hypnotic activities of threshold dose of pentobarbital sodium in mice showed that sleep duration in AL-1, AL-3, AL-5, and AL-7 groups were significantly prolonged (P < 0.05, 0.01), indicating these compounds had the hypnotic activities. Conclusion This study improves the synthesis process of pyrazolopyrimidine derivatives with simple operation, low cost, and high yield. And the pharmacodynamics of these compounds are preliminary evaluated through the behavioral observation method of mice, and to provide the direction for future synthesis research.