3-acetyl-4-ethoxy-1H-pyrrolo[2,3-b]pyridine | 1011711-61-7

• 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-acetyl-4-ethoxy-1H-pyrrolo[2,3-b]pyridine
• 英文别名: 1-(4-ethoxy-1H-pyrrolo[2,3-b]pyridin-3-yl)ethanone
• CAS: 1011711-61-7
• 化学式: C₁₁H₁₂N₂O₂
• 分子量: 204.228
• InChiKey: ABERHZYRGVPCBN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  55
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-acetyl-4-ethoxy-1H-pyrrolo[2,3-b]pyridine 、 苯磺酰氯 在 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 反应 4.0h， 以68%的产率得到3-acetyl-1-benzenesulfonyl-4-ethoxy-1H-pyrrolo[2,3-b]pyridine
  参考文献：
  名称：

  Meriolins (3-(Pyrimidin-4-yl)-7-azaindoles): Synthesis, Kinase Inhibitory Activity, Cellular Effects, and Structure of a CDK2/Cyclin A/Meriolin Complex

  摘要：

  We report the synthesis and biological characterization of 3-(pyrimidin-4-yl)-7-azaindoles (meriolins), a chemical hybrid between the natural products meridianins and variolins, derived from marine organisms. Meriolins display potent inhibitory activities toward cyclin-dependent kinases (CDKs) and, to a lesser extent, other kinases (GSK-3, DYRK1A). The crystal structures of 1e (meriolin 5) and variolin B (Bettayeb, K.; Tirado, O. M.; Marionneau-Lambert, S.; Ferandin, Y.; Lozach, O.; Morris, J.; Mateo-Lozano, S.; Druckes, P.; Schachtele, C.; Kubbutat, M.; Liger, F.; Marquet, B.; Joseph, B.; Echalier, A.; Endicott, J.; Notario, V.; Meijer, L. Cancer Res. 2007, 67, 8325-8334) in complex with CDK2/cyclin A reveal that the two inhibitors are orientated in very different ways inside the ATP-binding pocket of the kinase. A structure-activity relationship provides further insight into the molecular mechanism of action of this family of kinase inhibitors. Meriolins are also potent antiproliferative and proapoptotic agents in cells cultured either as monolayers or in spheroids. Proapoptotic efficacy of meriolins correlates best with their CDK2 and CDK9 inhibitory activity. Meriolins thus constitute a promising class of pharmacological agents to be further evaluated against the numerous human diseases that imply abnormal regulation of CDKs including cancers, neurodegenerative disorders, and polycystic kidney disease.

  DOI：

  10.1021/jm700940h
• 作为产物：
  描述：

  4-乙氧基-1H-吡咯并[2,3-B]吡啶 、 乙酸酐 在 三氟乙酸 作用下， 反应 8.0h， 以84%的产率得到3-acetyl-4-ethoxy-1H-pyrrolo[2,3-b]pyridine
  参考文献：
  名称：

  Meriolins (3-(Pyrimidin-4-yl)-7-azaindoles): Synthesis, Kinase Inhibitory Activity, Cellular Effects, and Structure of a CDK2/Cyclin A/Meriolin Complex

  摘要：

  We report the synthesis and biological characterization of 3-(pyrimidin-4-yl)-7-azaindoles (meriolins), a chemical hybrid between the natural products meridianins and variolins, derived from marine organisms. Meriolins display potent inhibitory activities toward cyclin-dependent kinases (CDKs) and, to a lesser extent, other kinases (GSK-3, DYRK1A). The crystal structures of 1e (meriolin 5) and variolin B (Bettayeb, K.; Tirado, O. M.; Marionneau-Lambert, S.; Ferandin, Y.; Lozach, O.; Morris, J.; Mateo-Lozano, S.; Druckes, P.; Schachtele, C.; Kubbutat, M.; Liger, F.; Marquet, B.; Joseph, B.; Echalier, A.; Endicott, J.; Notario, V.; Meijer, L. Cancer Res. 2007, 67, 8325-8334) in complex with CDK2/cyclin A reveal that the two inhibitors are orientated in very different ways inside the ATP-binding pocket of the kinase. A structure-activity relationship provides further insight into the molecular mechanism of action of this family of kinase inhibitors. Meriolins are also potent antiproliferative and proapoptotic agents in cells cultured either as monolayers or in spheroids. Proapoptotic efficacy of meriolins correlates best with their CDK2 and CDK9 inhibitory activity. Meriolins thus constitute a promising class of pharmacological agents to be further evaluated against the numerous human diseases that imply abnormal regulation of CDKs including cancers, neurodegenerative disorders, and polycystic kidney disease.

  DOI：

  10.1021/jm700940h

文献信息

• PYRROLO[2,3-B]PYRIDINE COMPOUNDS, AZAINDOLE COMPOUNDS USED FOR SYNTHESIZING SAID PYRROLO[2,3-B]PYRIDINE COMPOUNDS, METHODS FOR THE PRODUCTION THEREOF, AND USES THEREOF
  申请人：Meijer Laurent

  公开号：US20100184790A1

  公开（公告）日：2010-07-22

  The invention relates to pyrrolo[2,3-b]pyridine compounds and azaindole compounds used for the synthesis thereof. The invention also relates to methods for the production thereof and the uses thereof. Said novel pyrrolo[2,3-b]pyridine compounds according to the invention have great antiproliferative, apoptotic, and neuroprotective activities. The invention particularly applies to the pharmaceutical field.

  该发明涉及用于合成吡咯并[2,3-b]吡啶化合物和氮杂吲哚化合物的方法。该发明还涉及其生产方法和用途。根据该发明，所述新型吡咯并[2,3-b]吡啶化合物具有很强的抗增殖、凋亡和神经保护活性。该发明特别适用于药物领域。
• COMPOSES PYRROLO[2,3-B]PYRIDINE, COMPOSES AZAINDOLES UTILES DANS LA SYNTHESE DE CES COMPOSES PYRROLO[2,3-B]PYRIDINE, LEURS PROCEDES DE FABRICATION ET LEURS UTILISATIONS
  申请人：Centre National de la Recherche Scientifique

  公开号：EP2125803B1

  公开（公告）日：2013-04-10
• Meriolins (3-(Pyrimidin-4-yl)-7-azaindoles): Synthesis, Kinase Inhibitory Activity, Cellular Effects, and Structure of a CDK2/Cyclin A/Meriolin Complex
  作者：Aude Echalier、Karima Bettayeb、Yoan Ferandin、Olivier Lozach、Monique Clément、Annie Valette、François Liger、Bernard Marquet、Jonathan C. Morris、Jane A. Endicott、Benoît Joseph、Laurent Meijer

  DOI：10.1021/jm700940h

  日期：2008.2.1

  We report the synthesis and biological characterization of 3-(pyrimidin-4-yl)-7-azaindoles (meriolins), a chemical hybrid between the natural products meridianins and variolins, derived from marine organisms. Meriolins display potent inhibitory activities toward cyclin-dependent kinases (CDKs) and, to a lesser extent, other kinases (GSK-3, DYRK1A). The crystal structures of 1e (meriolin 5) and variolin B (Bettayeb, K.; Tirado, O. M.; Marionneau-Lambert, S.; Ferandin, Y.; Lozach, O.; Morris, J.; Mateo-Lozano, S.; Druckes, P.; Schachtele, C.; Kubbutat, M.; Liger, F.; Marquet, B.; Joseph, B.; Echalier, A.; Endicott, J.; Notario, V.; Meijer, L. Cancer Res. 2007, 67, 8325-8334) in complex with CDK2/cyclin A reveal that the two inhibitors are orientated in very different ways inside the ATP-binding pocket of the kinase. A structure-activity relationship provides further insight into the molecular mechanism of action of this family of kinase inhibitors. Meriolins are also potent antiproliferative and proapoptotic agents in cells cultured either as monolayers or in spheroids. Proapoptotic efficacy of meriolins correlates best with their CDK2 and CDK9 inhibitory activity. Meriolins thus constitute a promising class of pharmacological agents to be further evaluated against the numerous human diseases that imply abnormal regulation of CDKs including cancers, neurodegenerative disorders, and polycystic kidney disease.