(Z)-2-(6-methoxy-1H-indol-3-yl)-3-(5-methoxy-pyridin-3-yl)acrylonitrile

• 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: (Z)-2-(6-methoxy-1H-indol-3-yl)-3-(5-methoxy-pyridin-3-yl)acrylonitrile
• 英文别名: (Z)-2-(6-methoxy-1H-indol-3-yl)-3-(5-methoxypyridin-3-yl)prop-2-enenitrile
• 化学式: C₁₈H₁₅N₃O₂
• 分子量: 305.336
• InChiKey: BNIKUIPKSYWAGB-WLRTZDKTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  70.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (Z)-2-(6-methoxy-1H-indol-3-yl)-3-(5-methoxy-pyridin-3-yl)acrylonitrile 在 碘 作用下， 以 乙醇 为溶剂， 反应 14.0h， 以66%的产率得到1,9-dimethoxy-11H-pyrido[4,3-a]carbazole-6-carbonitrile
  参考文献：
  名称：

  Further investigation of Paprotrain: Towards the conception of selective and multi-targeted CNS kinase inhibitors

  摘要：

  Starting from a known compound, identified as the first inhibitor of the kinesin MKLP-2 and named Paprotrain, we have investigated its reactivity to produce through photochemistry a potent nanomolar inhibitor of the kinase DYRK1A.Using similar and different chemical pathways, we have designed several families of compounds that have been screened on a panel of five protein kinases: CK1 delta/epsilon, CDK5/p25, GSK3 alpha/beta, DYRKIA and CLK1, all involved in neurodegenerative disorders such as Alzheimer's disease.We have identified a first group of multi-targeted compounds, a second group of dual inhibitors of DYRKIA & CLK1 and a last group of selective inhibitors of CLK1.Then, our best submicromolar to nanomolar inhibitors were evaluated towards the closest members of the aforementioned kinases: DYRK1B and CLK4, as well as the subfamily CLK2-3.Several compounds appear to be particularly promising for the development of tools in the battle against Alzheimer's disease. (C) 2016 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2016.08.069
• 作为产物：
  描述：

  6-甲氧基吲哚-3-乙腈 、 5-甲氧基-吡啶-3-甲醛 在 sodium methylate 作用下， 以 乙醇 为溶剂， 反应 4.5h， 以80%的产率得到(Z)-2-(6-methoxy-1H-indol-3-yl)-3-(5-methoxy-pyridin-3-yl)acrylonitrile
  参考文献：
  名称：

  Further investigation of Paprotrain: Towards the conception of selective and multi-targeted CNS kinase inhibitors

  摘要：

  Starting from a known compound, identified as the first inhibitor of the kinesin MKLP-2 and named Paprotrain, we have investigated its reactivity to produce through photochemistry a potent nanomolar inhibitor of the kinase DYRK1A.Using similar and different chemical pathways, we have designed several families of compounds that have been screened on a panel of five protein kinases: CK1 delta/epsilon, CDK5/p25, GSK3 alpha/beta, DYRKIA and CLK1, all involved in neurodegenerative disorders such as Alzheimer's disease.We have identified a first group of multi-targeted compounds, a second group of dual inhibitors of DYRKIA & CLK1 and a last group of selective inhibitors of CLK1.Then, our best submicromolar to nanomolar inhibitors were evaluated towards the closest members of the aforementioned kinases: DYRK1B and CLK4, as well as the subfamily CLK2-3.Several compounds appear to be particularly promising for the development of tools in the battle against Alzheimer's disease. (C) 2016 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2016.08.069

文献信息

• [EN] KINASE INHIBITORS<br/>[FR] INHIBITEURS DE KINASES
  申请人：CENTRE NAT RECH SCIENT

  公开号：WO2014115071A1

  公开（公告）日：2014-07-31

  La présente invention concerne les dérivés d'indole, de benzothiophène ou de benzofurane de formule (I) Composé de formule (Ia) dans laquelle Y1 est choisi parmi un groupe NH, un atome de soufre ou un atome d'oxygène,Y2 est choisi parmi un groupe CH ou un atome d'azote,X1, X2, X3 et X4 représentent un groupe CH, un atome de carbone ou un atome d'azote, R4 représente un groupe -CN, un groupe -CONH2, un groupe -CH2NR5R6, un groupe -CH2NHCOCH3, un groupe (AA) ou un groupe (BB), Z représente un groupe CH ou un atome d'azote et Ar représente un groupe aryle, n représente un entier compris entre 1 et 4,ainsi que leurs sels pharmaceutiquement acceptables,pour leur utilisation dans le traitement de maladies neurodégénératives, de la dépression, de la skizophrénie ou des infections virales. Certains ce ces composés pouvant également être utiles dans le traitement du cancer. Elle concerne également certains composés correspondants nouveaux ainsi que leur procédé de préparation associé.
• Further investigation of Paprotrain: Towards the conception of selective and multi-targeted CNS kinase inhibitors
  作者：Christophe Labrière、Olivier Lozach、Mélina Blairvacq、Laurent Meijer、Catherine Guillou

  DOI：10.1016/j.ejmech.2016.08.069

  日期：2016.11

  Starting from a known compound, identified as the first inhibitor of the kinesin MKLP-2 and named Paprotrain, we have investigated its reactivity to produce through photochemistry a potent nanomolar inhibitor of the kinase DYRK1A.Using similar and different chemical pathways, we have designed several families of compounds that have been screened on a panel of five protein kinases: CK1 delta/epsilon, CDK5/p25, GSK3 alpha/beta, DYRKIA and CLK1, all involved in neurodegenerative disorders such as Alzheimer's disease.We have identified a first group of multi-targeted compounds, a second group of dual inhibitors of DYRKIA & CLK1 and a last group of selective inhibitors of CLK1.Then, our best submicromolar to nanomolar inhibitors were evaluated towards the closest members of the aforementioned kinases: DYRK1B and CLK4, as well as the subfamily CLK2-3.Several compounds appear to be particularly promising for the development of tools in the battle against Alzheimer's disease. (C) 2016 Elsevier Masson SAS. All rights reserved.