3-ethynyl-1H-pyrrolo[2,3-b]pyridine

• 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-ethynyl-1H-pyrrolo[2,3-b]pyridine
• 化学式: C₉H₆N₂
• 分子量: 142.16
• InChiKey: ATJRDGOAKWWOJY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 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-ethynyl-1H-pyrrolo[2,3-b]pyridine 、 2-乙酰氨基-3,4,6-三-O-乙酰基-2-脱氧-Β-D-吡喃葡萄糖酰基叠氮化物 在 sodium methylate 、 copper(II) sulfate 、 sodium ascorbate 作用下， 以 四氢呋喃 、 甲醇 、 水 、 叔丁醇 为溶剂， 反应 0.5h， 生成 4-(3-(7-azaindolyl))-1-(2'-acetamido-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：

  3-碘-7-氮杂吲哚 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 四丁基氟化铵 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 22.0h， 生成 3-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

文献信息

• Efficient and General Protocol for Sonogashira Cross-Coupling Reactions of Maleimides
  作者：Agathe Souffrin、Cécile Croix、Marie-Claude Viaud-Massuard

  DOI：10.1002/ejoc.201101811

  日期：2012.5

  Maleimides are involved for the first time in Sonogashira cross-coupling reactions. Sonogashira conditions have been developed to allow subsequent coupling of various terminal alkynes at room temperature in moderate to excellent yields. These results open the way to innovative synthesis strategies for various difunctionalized maleimide derivatives.

  马来酰亚胺首次参与 Sonogashira 交叉偶联反应。Sonogashira 条件已被开发以允许随后在室温下以中等至极好的产率偶联各种末端炔烃。这些结果为各种双官能化马来酰亚胺衍生物的创新合成策略开辟了道路。
• Design and synthesis of O-GlcNAcase inhibitors via ‘click chemistry’ and biological evaluations
  作者：Tiehai Li、Lina Guo、Yan Zhang、Jiajia Wang、Zhonghua Li、Lin Lin、Zhenxing Zhang、Lei Li、Jianping Lin、Wei Zhao、Jing Li、Peng George Wang

  DOI：10.1016/j.carres.2011.03.026

  日期：2011.7

  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.
• Synthesis, biological evaluation and molecular modeling of a novel series of 7-azaindole based tri-heterocyclic compounds as potent CDK2/Cyclin E inhibitors
  作者：Christine B. Baltus、Radek Jorda、Christophe Marot、Karel Berka、Václav Bazgier、Vladimír Kryštof、Gildas Prié、Marie-Claude Viaud-Massuard

  DOI：10.1016/j.ejmech.2015.12.023

  日期：2016.1

  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.