4-(3-(4-chlorophenoxy)propoxy)-3-methoxybenzaldehyde | 426222-63-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-(3-(4-chlorophenoxy)propoxy)-3-methoxybenzaldehyde
• 英文别名: Cambridge id 6439544；4-[3-(4-chlorophenoxy)propoxy]-3-methoxybenzaldehyde
• CAS: 426222-63-1
• 化学式: C₁₇H₁₇ClO₄
• 分子量: 320.773
• InChiKey: IPTWKOODEQACJL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  22
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  44.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-硫代乙内酰脲 、 4-(3-(4-chlorophenoxy)propoxy)-3-methoxybenzaldehyde 在 哌啶 作用下， 以 甲醇 为溶剂， 反应 1.0h， 以71%的产率得到(Z)-5-(4-(3-(4-chlorophenoxy)propoxy)-3-methoxybenzylidene)-2-thioxoimidazolidin-4-one
  参考文献：
  名称：

  Discovery of Novel Fibroblast Growth Factor Receptor 1 Kinase Inhibitors by Structure-Based Virtual Screening

  摘要：

  Fibroblast growth factors (FGFs) play important roles in embryonic development, angiogenesis, wound healing, and cell proliferation and differentiation. In search of inhibitors of FGFR1 kinase, 2.2 million compounds were docked into the ATP binding site of the protein. A co-crystal structure, which shows two alternative conformations for the nucleotide binding loop, is reported. Docking was performed oil both conformations and, ultimately, 23 diverse compounds were purchased and assayed. Following hit validation, two compounds 10 and 16, a benzylidene derivative of pseudothiohydantoin and a thienopyrimidinone derivative, respectively, were discovered that inhibit FGFR1 kinase with IC50 values of 23 and 50 mu M. Initial optimization of 16 led to the more unsaturated 40, which has significantly enhanced potency, 1.9 mu M. The core structures represent new structural motifs for FGFR1 kinase inhibitors. The study also illustrates complexities associated with the choice of protein structures for docking, possible use of multiple kinase structures to seek selectivity, and hit identification.

  DOI：

  10.1021/jm901386e
• 作为产物：
  描述：

  对氯苯酚 、 4-(3-bromopropoxy)-3-methoxybenzaldehyde 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 以54%的产率得到4-(3-(4-chlorophenoxy)propoxy)-3-methoxybenzaldehyde
  参考文献：
  名称：

  Discovery of Novel Fibroblast Growth Factor Receptor 1 Kinase Inhibitors by Structure-Based Virtual Screening

  摘要：

  Fibroblast growth factors (FGFs) play important roles in embryonic development, angiogenesis, wound healing, and cell proliferation and differentiation. In search of inhibitors of FGFR1 kinase, 2.2 million compounds were docked into the ATP binding site of the protein. A co-crystal structure, which shows two alternative conformations for the nucleotide binding loop, is reported. Docking was performed oil both conformations and, ultimately, 23 diverse compounds were purchased and assayed. Following hit validation, two compounds 10 and 16, a benzylidene derivative of pseudothiohydantoin and a thienopyrimidinone derivative, respectively, were discovered that inhibit FGFR1 kinase with IC50 values of 23 and 50 mu M. Initial optimization of 16 led to the more unsaturated 40, which has significantly enhanced potency, 1.9 mu M. The core structures represent new structural motifs for FGFR1 kinase inhibitors. The study also illustrates complexities associated with the choice of protein structures for docking, possible use of multiple kinase structures to seek selectivity, and hit identification.

  DOI：

  10.1021/jm901386e

文献信息

• Discovery of Novel Fibroblast Growth Factor Receptor 1 Kinase Inhibitors by Structure-Based Virtual Screening
  作者：Krishna P. Ravindranathan、Valsan Mandiyan、Anil R. Ekkati、Jae H. Bae、Joseph Schlessinger、William L. Jorgensen

  DOI：10.1021/jm901386e

  日期：2010.2.25

  Fibroblast growth factors (FGFs) play important roles in embryonic development, angiogenesis, wound healing, and cell proliferation and differentiation. In search of inhibitors of FGFR1 kinase, 2.2 million compounds were docked into the ATP binding site of the protein. A co-crystal structure, which shows two alternative conformations for the nucleotide binding loop, is reported. Docking was performed oil both conformations and, ultimately, 23 diverse compounds were purchased and assayed. Following hit validation, two compounds 10 and 16, a benzylidene derivative of pseudothiohydantoin and a thienopyrimidinone derivative, respectively, were discovered that inhibit FGFR1 kinase with IC50 values of 23 and 50 mu M. Initial optimization of 16 led to the more unsaturated 40, which has significantly enhanced potency, 1.9 mu M. The core structures represent new structural motifs for FGFR1 kinase inhibitors. The study also illustrates complexities associated with the choice of protein structures for docking, possible use of multiple kinase structures to seek selectivity, and hit identification.