新型吡唑并[3,4-d]嘧啶-4-酮类衍生物的结构表征和镇痛活性

本文以2-氰基-3-乙氧基丙烯酸乙酯与3,4-二甲基苯肼为原料，通过多步反应合成了三种新型吡唑并3,4-d]嘧啶-4-酮类衍生物（A~C），通过核磁共振（NMR，包括¹H NMR、¹³C NMR）和液相色谱-质谱联用（LC-MS）技术表征确证了其结构，并完整归属了三种化合物的¹H NMR数据．对所合成的化合物1-(3,4-二甲基苯基)-6-甲基-5-3-(哌啶-1-基)丙氧基]-1,5-二氢-4H-吡唑并3,4-d]嘧啶-4-酮（A），通过小鼠脑部质谱成像和福尔马林实验进行了初步的体内镇痛活性评价，我们发现化合物A能透过血脑屏障，并产生显著且剂量依赖的镇痛活性．本研究为以吡唑并3,4-d]嘧啶-4-酮为骨架的镇痛药物的研发提供了结构和体内活性的基础研究数据．

Structure Characterization and Analgesic Activity of Novel Pyrazolo[3,4-d]pyrimidin-4-one Derivatives

Three compounds of novel pyrazolo3,4-d]pyrimidin-4-one derivatives (A~C) were synthesized through a multi-step reaction using ethyl-2-cyano-3-ethoxyacrylate and 3,4-dimethylphenylhydrazine. The structures of these compounds were identified by nuclear magnetic resonance (NMR, i.e., ¹H NMR, ¹³C NMR), and liquid chromatography-mass spectrum (LC-MS), and the ¹H NMR signals of each compound were fully assigned. The in vivo analgesic activity of synthesized compound A was preliminarily evaluated through mass spectrometry brain imaging and formalin induced pain model in mice. The imaging data and results showed that compound A could cross the blood-brain barrier and penetrate into the brain of mice, and produce a dose-dependent analgesic activity. This study provided a piece of fundamental research data on structural and in vivo activity for developing anti-pain drugs based on pyrazolo3,4-d]pyrimidin-4-one scaffold.