3-((trimethylsilyl)ethynyl)-1H-pyrrolo[2,3-b]pyridine | 1312592-20-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并吡啶类
• 英文名称: 3-((trimethylsilyl)ethynyl)-1H-pyrrolo[2,3-b]pyridine
• 英文别名: 3-((trimethylsilyl)ethynyl)-7-azaindole；trimethyl-[2-(1H-pyrrolo[2,3-b]pyridin-3-yl)ethynyl]silane
• CAS: 1312592-20-3
• 化学式: C₁₂H₁₄N₂Si
• 分子量: 214.342
• InChiKey: DSPUIIQVGRHEAP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.79
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  28.7
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  3-((trimethylsilyl)ethynyl)-1H-pyrrolo[2,3-b]pyridine 在 四丁基氟化铵 、 copper(II) sulfate 、 sodium ascorbate 作用下， 以 四氢呋喃 、 水 、 叔丁醇 为溶剂， 反应 0.25h， 生成 4-(3-(7-azaindolyl))-1-(2'-acetamido-3',4',6'-tri-O-acetyl-2'-deoxy-β-D-glucopyranosyl)-1,2,3-triazole
  参考文献：
  名称：

  Design and synthesis of O-GlcNAcase inhibitors via ‘click chemistry’ and biological evaluations

  摘要：

  Protein O-GlcNAcylation has been shown to play an important role in a number of biological processes, including regulation of the cell cycle, DNA transcription and translation, signal transduction, and protein degradation. O-GlcNAcase (OGA) is responsible for the removal of O-linked beta-N-acetylglucosamine (O-GlcNAc) from serine or threonine residues, and thus plays a key role in O-GlcNAc metabolism. Potent OGA inhibitors are useful tools for studying the cellular processes of O-GlcNAc, and may be developed as drugs for the treatment neurodegenerative diseases. In this study, Cu(I)-catalyzed 'Click' cycloaddition reactions between glycosyl azides and alkynes were exploited to generate inhibitory candidates of OGA. Enzymatic kinetic screening revealed that compound 7 was a potent competitive inhibitor of human O-GlcNAcase (K(i) = 185.6 mu M). Molecular docking simulations of compound 7 into CpOGA (Clostridium perfringens OGA) suggested that strong pi-pi stacking interaction between the compound and W490 considerably contributed to improving the inhibitory activity. Crown Copyright (C) 2011 Published by Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.carres.2011.03.026
• 作为产物：
  描述：

  7-氮杂吲哚 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 碘 、 三乙胺 、 potassium iodide 、 sodium hydroxide 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 36.0h， 生成 3-((trimethylsilyl)ethynyl)-1H-pyrrolo[2,3-b]pyridine
  参考文献：
  名称：

  Synthesis, biological evaluation and molecular modeling of a novel series of 7-azaindole based tri-heterocyclic compounds as potent CDK2/Cyclin E inhibitors

  摘要：

  From four molecules, inspired by the structural features of fascaplysin, with an interesting potential to inhibit cyclin-dependent kinases (CDKs), we designed a new series of tri-heterocyclic derivatives based on 1H-pyrrolo[2,3-b]pyridine (7-azaindole) and triazole heterocycles. Using a Huisgen type [3 + 2] cycloaddition as the convergent key step, 24 derivatives were synthesized and their biological activities were evaluated. Comparative molecular field analysis (CoMFA), based on three-dimensional quantitative structure activity relationship (3D-QSAR) studies, was conducted on a series of 30 compounds from the literature with high to low known inhibitory activity towards CDK2/cyclin E and was validated by a test set of 5 compounds giving satisfactory predictive r(2) value of 0.92. Remarkably, it also gave a good prediction of pIC(50) for our tri-heterocyclic series which reinforce the validation of this model for the pIC(50) prediction of external set compounds. The most promising compound, 43, showed a micro -molar range inhibitory activity against CDK2/cyclin E and also an antiproliferative and proapoptotic activity against a panel of cancer cell lines. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.12.023