(4Z)-4-({[4-(4-methylpiperazin-1-yl)phenyl]amino}methylene)-6-(2-phenylvinyl)isoquinoline-1,3(2H,4H)-dione | 1033330-40-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: (4Z)-4-({[4-(4-methylpiperazin-1-yl)phenyl]amino}methylene)-6-(2-phenylvinyl)isoquinoline-1,3(2H,4H)-dione
• CAS: 1033330-40-3
• 化学式: C₂₉H₂₈N₄O₂
• 分子量: 464.567
• InChiKey: RNISWZFWAGIIIB-HACAOAEASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.33
• 重原子数：
  35.0
• 可旋转键数：
  5.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  64.68
• 氢给体数：
  2.0
• 氢受体数：
  5.0

反应信息

• 作为产物：
  描述：

  苯乙烯 、 (4Z)-6-bromo-4-({[4-(4-methylpiperazin-1-yl)phenyl]amino}methylene)isoquinoline-1,3(2H,4H)-dione 在 四丁基溴化铵 、 palladium diacetate 、 caesium carbonate 、 三(邻甲基苯基)磷 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.03h， 以13%的产率得到(4Z)-4-({[4-(4-methylpiperazin-1-yl)phenyl]amino}methylene)-6-(2-phenylvinyl)isoquinoline-1,3(2H,4H)-dione
  参考文献：
  名称：

  4-(Phenylaminomethylene)isoquinoline-1,3(2H,4H)-diones as Potent and Selective Inhibitors of the Cyclin-Dependent Kinase 4 (CDK4)

  摘要：

  The cyclin-dependent kinases (CDKs), as complexes with their respective partners, the cyclins, are critical regulators of cell cycle progression. Because aberrant regulations of CDK4/cyclin D1 lead to uncontrolled cell proliferation, a hallmark of cancer, small-molecule inhibitors of CDK4/cyclin D1 are attractive as prospective antitumor agents. The series of 4-(phenylaminomethylene)isoquinoline-1,3(2H,4H)-dione derivatives reported here represents a novel class of potent inhibitors that selectively inhibit CDK4 over CDK2 and CDK1 activities. In the headpiece of the 4-(phenylaminomethylene)isoquinoline-1,3(2H,4H)dione, a basic amine substitutent is required on the aniline ring for the CDK4 inhibitory activity. The inhibitory activity is further enhanced when an aryl or heteroaryl substituent is introduced at the C-6 position of the isoquinoline-1,3(2H,4H)-dione core. We present here SAR data and a CDK4 mimic model that explains the binding, potency, and selectivity of our CDK4 selective inhibitors.

  DOI：

  10.1021/jm800072z