三氮唑并吡啶类脯氨酸羟化酶抑制剂的设计合成研究
Design and Synthesis of Proline Hydroxylase Domain Inhibitor
DOI: 10.12677/SSC.2018.61001, PDF,    国家自然科学基金支持
作者: 刘思凡, 李庶心*：军事科学院军事医学研究院辐射医学研究所，北京；张 宇, 梁 欢：江西中医药大学研究生部，江西 南昌；杨 洋：广东药科大学药学院，广东 广州；胡文祥*：北京神剑天军医学科学院京东祥鹄微波化学联合实验室，北京
关键词: 脯氨酸羟化酶；脯氨酸羟化酶抑制剂；三氮唑并吡啶类化合物；Proline Hydroxylase Domain； Proline Hydroxylase Domain Inhibitor； Triazolopyridine Compounds
摘要: 目的：设计并合成新的三氮唑并吡啶类脯氨酸羟化酶抑制剂。方法：以JTZ-951为先导化合物，借助乌尔曼反应等方法合成三氮唑并吡啶类化合物。该类化合物的作用机理为与内源2-酮戊二酸分子形成竞争,从而抑制脯氨酸羟化酶的活性。通过控制变量的方法对关键合成步骤进行了方法学研究。结果与结论：合成了5个化合物均未见文献报道，其结构经核磁共振氢谱、质谱、元素分析鉴定。并在参考文献合成方法的基础上，对文献方法进行较大改进，建立了这类化合物的合成路线。
Abstract: Aim: To design and synthesize new proline hydroxylase domain inhibitors. Methods: JTZ-951 is concerned as lead compound. Via Ullmann reaction, triazopyrazole compounds which can compete with endogenous 2-ketoglutarate molecules thereby inhibiting activity of proline hydroxylase are synthesized. Studies on methods of key synthetic steps are also rendered in this paper by means of control variable. Results and conclusion: 5 Target compounds were synthesized. Their structure was identified by 1H NMR, MS and elemental analysis. The literature method is greatly improved, and the synthetic route of these compounds is obtained.
文章引用：刘思凡, 张宇, 杨洋, 梁欢, 胡文祥, 李庶心. 三氮唑并吡啶类脯氨酸羟化酶抑制剂的设计合成研究[J]. 合成化学研究, 2018, 6(1): 1-7. https://doi.org/10.12677/SSC.2018.61001

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