2-((4-(1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-1,2,3-triazol-1-yl)methyl)-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: 2-((4-(1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-1,2,3-triazol-1-yl)methyl)-1H-pyrrolo[2,3-b]pyridine
• 英文别名: 2-[1-(1H-pyrrolo[2,3-b]pyridin-2-ylmethyl)triazol-4-yl]-1H-pyrrolo[2,3-b]pyridine
• 化学式: C₁₇H₁₃N₇
• 分子量: 315.337
• InChiKey: AUIXWRGNKGACOG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  88.1
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  1H-吡咯并[2,3-b]吡啶-2-羧酸乙酯 在 copper(l) iodide 、 lithium aluminium tetrahydride 、 氯化亚砜 、 四丁基氟化铵 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 乙二醇二甲醚 、 二氯甲烷 为溶剂， 反应 49.0h， 生成 2-((4-(1H-pyrrolo[2,3-b]pyridin-2-yl)-1H-1,2,3-triazol-1-yl)methyl)-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

• 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.