4-{4-[(4-methylpiperazin-1-yl)-phenylamino]-methylene}-6-m-acetylphenylamino-4H-isoquinoline-1,3-dione | 1042409-56-2

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-{4-[(4-methylpiperazin-1-yl)-phenylamino]-methylene}-6-m-acetylphenylamino-4H-isoquinoline-1,3-dione
• 英文别名: 6-(3-acetylanilino)-4-[[4-(4-methylpiperazin-1-yl)anilino]methylidene]isoquinoline-1,3-dione
• CAS: 1042409-56-2
• 化学式: C₂₉H₂₉N₅O₃
• 分子量: 495.581
• InChiKey: JMLAPNWNKUCNEK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.11
• 重原子数：
  37.0
• 可旋转键数：
  6.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  93.78
• 氢给体数：
  3.0
• 氢受体数：
  7.0

反应信息

• 作为产物：
  描述：

  6-bromo-4-{4-[(4-methylpiperazin-1-yl)-phenylamino]methylene}-4H-isoquinoline-1,3-dione 、 间氨基苯乙酮 在 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 allylchloro[1,3-bis(2,6-di-isopropylphenyl)imidazol-2-ylidine]palladium(II) 、 potassium tert-butylate 作用下， 以 N-甲基吡咯烷酮 为溶剂， 反应 0.25h， 以29 mg的产率得到4-{4-[(4-methylpiperazin-1-yl)-phenylamino]-methylene}-6-m-acetylphenylamino-4H-isoquinoline-1,3-dione
  参考文献：
  名称：

  Lead identification to generate isoquinolinedione inhibitors of insulin-like growth factor receptor (IGF-1R) for potential use in cancer treatment

  摘要：

  Insulin-like growth factor receptor (IGF-1R) is a growth factor receptor tyrosine kinase that acts as a critical mediator of cell proliferation and survival. This receptor is over-expressed or activated in tumor cells and is emerging as a novel target in cancer therapy. Efforts in our "Hit to Lead'' group have generated a novel series of submicromolar IGF-1R inhibitors based on a isoquinolinedione template originating from a Lance enzyme HTS screen. Chemical triage and parallel synthesis incorporating focused library arrays were instrumental in moving these investigations through the Wyeth exploratory medicinal chemistry process. The strategies, synthesis, and SAR behind this interesting kinase scaffold will be described. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.04.044