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  

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

作　　者：李华斌[1] 朱有全[1] 宋晓薇[1] 牛子霞[1] 胡方中[1] 刘斌[1] 邹小毛[1] 杨华铮[1] 

机构地区：[1]南开大学元素有机化学研究所元素有机化学国家重点实验室,天津300071

出　　处：《有机化学》2009年第6期909-915,共7页Chinese Journal of Organic Chemistry

基　　金：国家重点基础研究发展计划(973计划)(No.2003CB114400);国家自然科学基金(Nos.20372040;20772066);国家高等教育博士点基金资助项目

摘　　要：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.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-carboxamide derivatives prepared by a reaction of substituted 5-amino-pyrazole-4-carbonyl chloride with substituted anilines. Different halides were reacted with 3f to afford the pure target products 3g-3w respectively. Their structures were identified by IH NMR, IR spectra and elemental analyses. The bioassay results showed that some of the title compounds exhibited high inhibition against protoporphyrinogen oxidase activity in vitro. The structure-activity relationship was discussed.

关 键 词：3H-吡唑并[3  4-d][1  2  3]三嗪-4-酮 合成 原卟啉原氧化酶 生物活性 

分 类 号：TQ450.21[化学工程—农药化工]