5H-pyrimido-[5,4-b]indole-4-carboxylic acid | 1438393-76-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并嘧啶类
• 英文名称: 5H-pyrimido-[5,4-b]indole-4-carboxylic acid
• 英文别名: 5h-Pyrimido-[5,4-b]indole-4-carboxylic acid；5H-pyrimido[5,4-b]indole-4-carboxylic acid
• CAS: 1438393-76-0
• 化学式: C₁₁H₇N₃O₂
• 分子量: 213.195
• InChiKey: MXWLUDHMFHUXIS-UHFFFAOYSA-N

物化性质

• 沸点：
  535.1±30.0 °C(Predicted)
• 密度：
  1.579±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  78.9
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5H-pyrimido-[5,4-b]indole-4-carboxylic acid 在 aluminum (III) chloride 、 草酰氯 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 为溶剂， 反应 22.0h， 生成 (4-methoxynaphthalen-1-yl)(5H-pyrimido[5,4-b]indol-4-yl)methanone
  参考文献：
  名称：

  Design and Synthesis of Aza-β-Carboline Analogs and their Antibacterial Evaluation

  摘要：

  由于近几十年来抗生素的过度使用，细菌耐药性已成为一个日益严重的全球性问题。通过应用 1,3,5-三嗪和 3-氨基吲哚的逆电子需求 Diels-Alder（IEDDA）反应，设计了两个 5H-嘧啶并[5,4-b]吲哚-4-甲酰胺和 5H-嘧啶并[5,4-b]吲哚-4-酮的小型重点文库，作为 eudistomin Y3 和 1-乙酰基-β-咔啉（1-ABC）类似物。研究发现，化合物 2a 和 2b 对牛分枝杆菌卡介苗具有活性，最低抑菌浓度（MICs）分别为 25 和 50 μg/mL，而化合物 2e 对所测试的三种白色念珠菌菌株均具有活性，最低抑菌浓度为 50 μg/mL。此外，化合物 2e 与氟康唑具有协同抗菌活性，这表明该类化合物的未来候选药物可与现有药物联合使用，治疗白色念珠菌感染。

  DOI：

  10.1007/s11094-021-02429-6
• 作为产物：
  描述：

  3-吲哚甲酸 在 盐酸 、 叠氮磷酸二苯酯 、 三乙胺 作用下， 以 四氢呋喃 、 水 、 二甲基亚砜 、 乙酸乙酯 为溶剂， 反应 75.0h， 生成 5H-pyrimido-[5,4-b]indole-4-carboxylic acid
  参考文献：
  名称：

  Total Synthesis of 4-Azaeudistomin Y1 and Analogues by Inverse-Electron­Demand Diels-Alder Reactions of 3-Aminoindoles with 1,3,5-Triazines

  摘要：

  A new inverse-electron-demand Diels-Alder (IDA) reaction of 3-aminoindoles as dienophiles was developed for the efficient preparation of 4-aza-beta-carbolines in high yields. Because N-1-unprotected 3-aminoindoles show poor thermal stability, a one-pot protocol was developed that combines the removal of tert-butoxycarbonyl protecting groups with the IDA reaction. This protocol, using tert-butyl 1H-indol-3-ylcarbamates as reactants, gave the corresponding IDA products in excellent yields. The new IDA methodology was used in a total synthesis of 4-azaeudistomin Y-1, which was obtained in 57% overall yield in four steps. Moreover, the chemistry is suitable for the rapid preparation, through either Friedel-Crafts acylation or amide-formation reactions, of analogues that are useful for exploring structure-activity relationships at the C-1-position.

  DOI：

  10.1055/s-0032-1316857

文献信息

• Total Synthesis of 4-Azaeudistomin Y1 and Analogues by Inverse-Electron­Demand Diels-Alder Reactions of 3-Aminoindoles with 1,3,5-Triazines
  作者：Qun Dang、Xu Bai、Guoxing Xu、Lianyou Zheng

  DOI：10.1055/s-0032-1316857

  日期：——

  A new inverse-electron-demand Diels-Alder (IDA) reaction of 3-aminoindoles as dienophiles was developed for the efficient preparation of 4-aza-beta-carbolines in high yields. Because N-1-unprotected 3-aminoindoles show poor thermal stability, a one-pot protocol was developed that combines the removal of tert-butoxycarbonyl protecting groups with the IDA reaction. This protocol, using tert-butyl 1H-indol-3-ylcarbamates as reactants, gave the corresponding IDA products in excellent yields. The new IDA methodology was used in a total synthesis of 4-azaeudistomin Y-1, which was obtained in 57% overall yield in four steps. Moreover, the chemistry is suitable for the rapid preparation, through either Friedel-Crafts acylation or amide-formation reactions, of analogues that are useful for exploring structure-activity relationships at the C-1-position.
• Design and Synthesis of Aza-β-Carboline Analogs and their Antibacterial Evaluation
  作者：Guoxing Xu、Qi Wei、Fuhang Song、Huanqin Dai、Lihua Deng、Xiaoping Zhou、Lixin Zhang、Qun Dang、Xu Bai

  DOI：10.1007/s11094-021-02429-6

  日期：——

  Bacterial drug resistance has become a growing problem worldwide due to the excessive use of antibiotics in recent decades. Two small focused libraries of 5H-pyrimido[5,4-b]indole-4-carboxamides and 5H-pyrimido-[5,4-b]indole-4-ketones were designed as eudistomin Y3 and 1-acetyl-β-carboline (1-ABC) analogs and prepared via application of Inverse Electron-Demand Diels-Alder (IEDDA) reaction of 1,3,5-triazines and 3-aminoindoles. Compounds 2a and 2b were discovered to have activity against Mycobacterium bovis BCG with Minimum Inhibitory Concentration (MICs) values of 25 and 50 μg/mL respectively while compound 2e was against all three strains of Candida albicans tested with MIC values of 50 μg/mL. Moreover, compound 2e demonstrated synergistic antibacterial activity with fluconazol, which suggested that future drug candidates from this class of compounds could be used in combination with existing drugs to treat C. albicans infections.

  由于近几十年来抗生素的过度使用，细菌耐药性已成为一个日益严重的全球性问题。通过应用 1,3,5-三嗪和 3-氨基吲哚的逆电子需求 Diels-Alder（IEDDA）反应，设计了两个 5H-嘧啶并[5,4-b]吲哚-4-甲酰胺和 5H-嘧啶并[5,4-b]吲哚-4-酮的小型重点文库，作为 eudistomin Y3 和 1-乙酰基-β-咔啉（1-ABC）类似物。研究发现，化合物 2a 和 2b 对牛分枝杆菌卡介苗具有活性，最低抑菌浓度（MICs）分别为 25 和 50 μg/mL，而化合物 2e 对所测试的三种白色念珠菌菌株均具有活性，最低抑菌浓度为 50 μg/mL。此外，化合物 2e 与氟康唑具有协同抗菌活性，这表明该类化合物的未来候选药物可与现有药物联合使用，治疗白色念珠菌感染。