N-(4-chlorophenyl)-9H-pyrido[2,3-b]indol-amine | 1600515-53-4

• 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: N-(4-chlorophenyl)-9H-pyrido[2,3-b]indol-amine
• 英文别名: N-(4-chlorophenyl)-9H-pyrido[2,3-b]indol-4-amine
• CAS: 1600515-53-4
• 化学式: C₁₇H₁₂ClN₃
• 分子量: 293.755
• InChiKey: WDVRZTDWJNHZTE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  40.7
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  9H-吡啶并[2,3-B]吲哚 在 双氧水 、 溶剂黄146 、 三氯氧磷 作用下， 以 N-甲基吡咯烷酮 、 N,N-二甲基甲酰胺 为溶剂， 生成 N-(4-chlorophenyl)-9H-pyrido[2,3-b]indol-amine
  参考文献：
  名称：

  Novel inhibitors of breast cancer relevant kinases Brk and HER2

  摘要：

  发现了一种新型的4-氨基吡啶[2,3-b]吲哚作为乳腺癌相关蛋白激酶Brk的抑制剂。在这一系列化合物中，具有良好特性的氨基取代基已被表征。对分子骨架取代基的组合进行了进一步研究，导致了额外的纳摩尔级Brk抑制剂。由于已有研究报告Brk在通过HER2激活促进乳腺癌进展中的作用，我们确定了我们新型Brk抑制剂的抑制特性，以额外抑制HER2。这些研究表征了首个同时作用于Brk和HER2的抑制剂以及首个专门针对HER2的抑制剂。

  DOI：

  10.1039/c4md00028e

文献信息

• Novel inhibitors of breast cancer relevant kinases Brk and HER2
  作者：Kazem Ahmed Mahmoud、Tom Wersig、Inna Slynko、Frank Totzke、Christoph Schächtele、Markus Oelze、Wolfgang Sippl、Christoph Ritter、Andreas Hilgeroth

  DOI：10.1039/c4md00028e

  日期：——

  Novel 4-anilino pyrido[2,3-b]indoles have been discovered as inhibitors of the breast cancer relevant protein kinase Brk. Within this first series favourable aniline substituents have been characterized. Combinations with substituents of the molecular scaffold have been further investigated and led to additional nanomolar Brk inhibitors. Due to the reported role of Brk in breast cancer progression via HER2 activation we determined the inhibition profile of our novel Brk inhibitors to additionally inhibit HER2. These studies characterized the first dually acting Brk and HER2 inhibitor and the first exclusive HER2 inhibitors.

  发现了一种新型的4-氨基吡啶[2,3-b]吲哚作为乳腺癌相关蛋白激酶Brk的抑制剂。在这一系列化合物中，具有良好特性的氨基取代基已被表征。对分子骨架取代基的组合进行了进一步研究，导致了额外的纳摩尔级Brk抑制剂。由于已有研究报告Brk在通过HER2激活促进乳腺癌进展中的作用，我们确定了我们新型Brk抑制剂的抑制特性，以额外抑制HER2。这些研究表征了首个同时作用于Brk和HER2的抑制剂以及首个专门针对HER2的抑制剂。
• Discovery of 4-anilino α-carbolines as novel Brk inhibitors
  作者：Kazem Ahmed Mahmoud、Martin Krug、Tom Wersig、Inna Slynko、Christoph Schächtele、Frank Totzke、Wolfgang Sippl、Andreas Hilgeroth

  DOI：10.1016/j.bmcl.2014.03.002

  日期：2014.4

  Dysregulation of cell signalling processes caused by an enhanced activity of protein kinases mainly contributes to cancer progression. Protein kinase inhibitors have been established as promising drugs that inhibit such overactive protein kinases in cancer cells. The formation of metastases, which makes a therapy difficult, remains a great challenge for cancer treatment. Recently, breast tumor kinase (Brk) was discovered as novel and interesting target for a cancer therapy because Brk participates in both cell dysregulation and metastasis. We discovered 4-anilino substituted a-carboline compounds as a novel class of highly active Brk inhibitors. In the current work, structure-activity relationships are discussed including docking results obtained for 4-anilino alpha-carbolines. A first profiling of selective kinase inhibition and a proof of concept for the antiproliferative effects is demonstrated. These results qualify the compounds as a promising class of novel antitumor agents. (c) 2014 Elsevier Ltd. All rights reserved.