9-chloro-2-{[5-[3-(dimethylamino)propyl]-2-(trifluoromethoxy)phenyl]amino}-5,7-dihydro-6H-pyrimido[5,4-d][1]benzazepin-6-one hydrochloride | 1350816-38-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯氮卓类
• 英文名称: 9-chloro-2-{[5-[3-(dimethylamino)propyl]-2-(trifluoromethoxy)phenyl]amino}-5,7-dihydro-6H-pyrimido[5,4-d][1]benzazepin-6-one hydrochloride
• CAS: 1350816-38-4
• 化学式: C₂₄H₂₃ClF₃N₅O₂*ClH
• 分子量: 542.388
• InChiKey: SAKIFJAXWPSJMI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.85
• 重原子数：
  36.0
• 可旋转键数：
  7.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  79.38
• 氢给体数：
  2.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  9-chloro-2-{[5-[3-(dimethylamino)propyl]-2-(trifluoromethoxy)phenyl]amino}-5,7-dihydro-6H-pyrimido[5,4-d][1]benzazepin-6-one hydrochloride 在 劳森试剂 作用下， 以 四氢呋喃 为溶剂， 以32%的产率得到9-chloro-2-{[5-[3-(dimethylamino)propyl]-2-(trifluoromethoxy)phenyl]amino}-5,7-dihydro-6H-pyrimido[5,4-d][1]benzazepine-6-thione
  参考文献：
  名称：

  Discovery of a Potent and Orally Bioavailable Benzolactam-Derived Inhibitor of Polo-Like Kinase 1 (MLN0905)

  摘要：

  This article describes the discovery of a series of potent inhibitors of Polo-like kinase 1 (PLK1). Optimization of this benzolactam-derived chemical series produced an orally bioavailable inhibitor of PLK1 (12c, MLN0905). In vivo pharmacokinetic-pharmacodynamic experiments demonstrated prolonged mitotic arrest after oral administration of 12c to tumor bearing nude mice. A subsequent efficacy study in nude mice achieved tumor growth inhibition or regression in a human colon tumor (HT29) xenograft model.

  DOI：

  10.1021/jm2011172
• 作为产物：
  描述：

  8-chloro-2,5-dioxo-2,3,4,5-tetrahydro-1H-benzo[b]azepine-4-carboxylic acid methyl ester 在 水 、 potassium carbonate 作用下， 以 四氢呋喃 、 乙醇 、 二甲基亚砜 为溶剂， 反应 2.0h， 生成 9-chloro-2-{[5-[3-(dimethylamino)propyl]-2-(trifluoromethoxy)phenyl]amino}-5,7-dihydro-6H-pyrimido[5,4-d][1]benzazepin-6-one hydrochloride
  参考文献：
  名称：

  Discovery of a Potent and Orally Bioavailable Benzolactam-Derived Inhibitor of Polo-Like Kinase 1 (MLN0905)

  摘要：

  This article describes the discovery of a series of potent inhibitors of Polo-like kinase 1 (PLK1). Optimization of this benzolactam-derived chemical series produced an orally bioavailable inhibitor of PLK1 (12c, MLN0905). In vivo pharmacokinetic-pharmacodynamic experiments demonstrated prolonged mitotic arrest after oral administration of 12c to tumor bearing nude mice. A subsequent efficacy study in nude mice achieved tumor growth inhibition or regression in a human colon tumor (HT29) xenograft model.

  DOI：

  10.1021/jm2011172