3-(2-氟-4-氯-5-取代基苯基)-7-甲基-3H-吡唑并[3,4-d][1,2,3]三嗪- 4(7H)-酮化合物的合成及其对原卟啉原氧化酶的抑制活性

为了发现新型的原卟啉原氧化酶抑制剂, 根据生物合理设计方法, 设计并合成了一系列的结构新颖的3H-吡唑并3,4-d]1,2,3]三嗪-4-酮衍生物. 利用不同取代的5-氨基-吡唑-4-甲酰氯与取代苯胺反应制得的5-氨基-N-苯基-1H-吡 唑-4-甲酰胺衍生物, 经进一步重氮化得到目标化合物, 并对化合物3f进行衍生化. 所得目标化合物的结构均经1H NMR, IR和元素分析确证. 生物活性测定结果表明, 部分化合物对原卟啉原氧化酶有较高的抑制活性, 讨论了其结构与活性的关系.

Synthesis and Protoporphyrinogen Oxidase Activity Inhibition of 3-(4-Chloro-2-fluoro-5-substitunt-phenyl)-7-methyl- 3H-pyrazolo[3,4-d] [1,2,3]triazin-4(7H)-ones

In order to find new protoporphyrinogen oxidase inhibitors, a series of novel 3H-pyrazolo- 3,4-d]1,2,3]triazin-4-one derivatives were designed and synthesized according to biorational design. The target molecules were synthesized by diazotization of different 5-amino-N-phenyl-1H-pyrazole-4- carbox-amide derivatives prepared by a reaction of substituted 5-amino-pyrazole-4-carbonyl chloride with substi-tuted anilines. Different halides were reacted with 3f to afford the pure target products 3g～3w respectively. Their structures were identified by 1H NMR, IR spectra and elemental analyses. The bioassay results showed that some of the title compounds exhibited high inhibition against protoporphyrinogen oxidase activity in vi-tro. The structure-activity relationship was discussed.