N-acetyl-N-(4-methyl-3,4,5,6-tetrahydro-2H-[1,2']bipyrazinyl-5'-yl)acetamide | 1033330-47-0

• 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: N-acetyl-N-(4-methyl-3,4,5,6-tetrahydro-2H-[1,2']bipyrazinyl-5'-yl)acetamide
• CAS: 1033330-47-0
• 化学式: C₁₃H₁₉N₅O₂
• 分子量: 277.326
• InChiKey: LLUVDBVGRZPAIL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.13
• 重原子数：
  20.0
• 可旋转键数：
  2.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  69.64
• 氢给体数：
  0.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  N-acetyl-N-(4-methyl-3,4,5,6-tetrahydro-2H-[1,2']bipyrazinyl-5'-yl)acetamide 在 盐酸 、 水 作用下， 以57%的产率得到5-(4-甲基哌嗪-1-基)吡嗪-2-胺
  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
• 作为产物：
  描述：

  N-甲基哌嗪 、 N-acetyl-N-(5-bromopyrazin-2-yl)acetamide 在 tris-(dibenzylideneacetone)dipalladium(0) 、 三叔丁基膦 、 potassium tert-butylate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.33h， 以35%的产率得到N-acetyl-N-(4-methyl-3,4,5,6-tetrahydro-2H-[1,2']bipyrazinyl-5'-yl)acetamide
  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