2-amino-4-(6-methoxy-1H-indol-3-yl)pyrimidine | 1538583-18-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 2-amino-4-(6-methoxy-1H-indol-3-yl)pyrimidine
• 英文别名: 4-(6-Methoxy-1H-indol-3-YL)pyrimidin-2-amine；4-(6-methoxy-1H-indol-3-yl)pyrimidin-2-amine
• CAS: 1538583-18-4
• 化学式: C₁₃H₁₂N₄O
• 分子量: 240.264
• InChiKey: UXLNLEOFOWUONW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  76.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  3-碘-6-甲氧基-1H-吲哚 在 四(三苯基膦)钯 、 sodium hydride 、 caesium carbonate 作用下， 以 1,4-二氧六环 、 甲醇 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 21.0h， 生成 2-amino-4-(6-methoxy-1H-indol-3-yl)pyrimidine
  参考文献：
  名称：

  Developing DYRK inhibitors derived from the meridianins as a means of increasing levels of NFAT in the nucleus

  摘要：

  A structure-activity relationship has been developed around the meridianin scaffold for inhibition of Dyrk1a. The compounds have been focussed on the inhibition of kinase Dyrk1a, as a means to retain the transcription factor NFAT in the nucleus. NFAT is responsible for up-regulation of genes responsible for the induction of a slow, oxidative skeletal muscle phenotype, which may be an effective treatment for diseases where exercise capacity is compromised. The SAR showed that while strong Dyrk1a binding was possible with the meridianin scaffold the compounds have no effect on NFAT localisation, however, by moving from the indole to a 6-azaindole scaffold both potent Dyrk1a binding and increased NFAT residence time in the nucleus were obtained - properties not observed with the reported Dyrk1a inhibitors. One compound was shown to be effective in an ex vivo muscle fiber assay. The increased biological activity is thought to arise from the added interaction between the azaindole nitrogen and the lysine residue in the back pocket. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2017.03.037

文献信息

• Protecting-Group-Free Synthesis of Meridianin A–G and Derivatives and Its Antibiofilm Evaluation
  作者：Huidan Geng、Fei Chen、Yonglong Zhao、Bing Guo、Lei Tang、Yuan-Yong Yang

  DOI：10.1021/acs.joc.2c02837

  日期：2023.3.17

  Herein, a protecting-group-free protocol was developed to realize a time and step economy diversification of the Meridianin alkaloid. A broad range of substituents are tolerated to deliver the products in moderate to high yields, and the first synthesis of Meridianin B was achieved. The simplicity of this protocol enables the rapid construction of a Meridianin derivative library for antibiofilm evaluation

  在此，开发了一种无保护基团的方案，以实现 Meridianin 生物碱的时间和步骤经济多样化。广泛的取代基可以以中等到高的产率提供产品，并且实现了 Meridianin B 的首次合成。该协议的简单性使得能够快速构建用于抗生物膜评估的 Meridianin 衍生物库。初步结果表明，经络宁衍生物能够协同抑制鲍曼不动杆菌生物膜并降低抗生素 MIC。
• Concise Syntheses of Meridianins and Meriolins Using a Catalytic Domino Amino-Palladation Reaction
  作者：Scott R. Walker、Milena L. Czyz、Jonathan C. Morris

  DOI：10.1021/ol403390m

  日期：2014.2.7

  A synthesis of natural and synthetic members of the meridianin family of kinase inhibitory natural products has been developed. The sequence utilizes a variation of the Cacchi palladium-catalyzed domino reaction to efficiently construct the heterocyclic framework of the meridianins and meriolins from monocyclic precursors.
• Developing DYRK inhibitors derived from the meridianins as a means of increasing levels of NFAT in the nucleus
  作者：Simon J. Shaw、Dane A. Goff、Nan Lin、Rajinder Singh、Wei Li、John McLaughlin、Kristen A. Baltgalvis、Donald G. Payan、Todd M. Kinsella

  DOI：10.1016/j.bmcl.2017.03.037

  日期：2017.6

  A structure-activity relationship has been developed around the meridianin scaffold for inhibition of Dyrk1a. The compounds have been focussed on the inhibition of kinase Dyrk1a, as a means to retain the transcription factor NFAT in the nucleus. NFAT is responsible for up-regulation of genes responsible for the induction of a slow, oxidative skeletal muscle phenotype, which may be an effective treatment for diseases where exercise capacity is compromised. The SAR showed that while strong Dyrk1a binding was possible with the meridianin scaffold the compounds have no effect on NFAT localisation, however, by moving from the indole to a 6-azaindole scaffold both potent Dyrk1a binding and increased NFAT residence time in the nucleus were obtained - properties not observed with the reported Dyrk1a inhibitors. One compound was shown to be effective in an ex vivo muscle fiber assay. The increased biological activity is thought to arise from the added interaction between the azaindole nitrogen and the lysine residue in the back pocket. (C) 2017 Elsevier Ltd. All rights reserved.