4-((1-methyl-1H-indol-3-yl)methylene)-3-(thiazol-2-yl)-1H-pyrazol-5(4H)-one

• 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: 4-((1-methyl-1H-indol-3-yl)methylene)-3-(thiazol-2-yl)-1H-pyrazol-5(4H)-one
• 英文别名: (4Z)-4-[(1-methylindol-3-yl)methylidene]-3-(1,3-thiazol-2-yl)-1H-pyrazol-5-one
• 化学式: C₁₆H₁₂N₄OS
• 分子量: 308.363
• InChiKey: KHZWCWOAQSMPGM-WQLSENKSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  87.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2-乙酰基噻唑 在 哌啶 、 H₄N₂*HO^(1-) 、 sodium hydride 作用下， 以 乙醇 、 甲苯 为溶剂， 生成 4-((1-methyl-1H-indol-3-yl)methylene)-3-(thiazol-2-yl)-1H-pyrazol-5(4H)-one
  参考文献：
  名称：

  Structure-guided identification of novel VEGFR-2 kinase inhibitors via solution phase parallel synthesis

  摘要：

  Structural analysis of the essential binding elements of the oxindole-based kinase inhibitor (1) led to the identification of a novel class of heterocyclic-substituted pyrazolones. Knoevenagel condensation of a variety of activated methylene nucleophiles with indole or pyrrole carboxaldehydes provided a focused library of molecules, each containing elements of kinase pharmacophore probe. Initial screening for VEGFR-2 kinase inhibit ion eliminated several of the probes. Identification of ail active pyrazolone motif and further optimization resulted in several highly potent VEGFR-2 inhibitors with cellular efficacy, anti-angiogenic activity ex vivo in rat aortic ring explant cultures, and oral anti-tumor efficacy in nude mice. (C) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.01.063