6-{4-[(4-methylpiperazin-1-yl)sulfonyl]phenyl}-3-oxo-N-(pyridin-3-yl)-3,4-dihydropyrazine-2-carboxamide | 1374577-40-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 6-{4-[(4-methylpiperazin-1-yl)sulfonyl]phenyl}-3-oxo-N-(pyridin-3-yl)-3,4-dihydropyrazine-2-carboxamide
• 英文别名: 5-[4-(4-methylpiperazin-1-yl)sulfonylphenyl]-2-oxo-N-pyridin-3-yl-1H-pyrazine-3-carboxamide
• CAS: 1374577-40-8
• 化学式: C₂₁H₂₂N₆O₄S
• 分子量: 454.509
• InChiKey: VRGDOBUGBOAEOH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  32
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  132
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  6-{4-[(4-methylpiperazin-1-yl)sulfonyl]phenyl}-3-oxo-N-(pyridin-3-yl)-3,4-dihydropyrazine-2-carboxamide 在 三氯氧磷 作用下， 反应 3.0h， 以61%的产率得到3-chloro-6-{4-[(4-methylpiperazin-1-yl)sulfonyl]phenyl}-N-(pyridin-3-yl)pyrazine-2-carboxamide
  参考文献：
  名称：

  Discovery of Novel Potent and Highly Selective Glycogen Synthase Kinase-3β (GSK3β) Inhibitors for Alzheimer’s Disease: Design, Synthesis, and Characterization of Pyrazines

  摘要：

  Glycogen synthase kinase-3 beta, also called tau phosphorylating kinase, is a proline-directed serine/threonine kinase which was originally identified due to its role in glycogen metabolism. Active forms of GSK3 beta localize to pretangle pathology including dystrophic neuritis and neurofibrillary tangles in Alzheimer's disease (AD) brain. By using a high throughput screening (HTS) approach to search for new chemical series and cocrystallization of key analogues to guide the optimization and synthesis of our pyrazine series, we have developed highly potent and selective inhibitors showing cellular efficacy and blood-brain barrier penetrance. The inhibitors are suitable for in vivo efficacy testing and may serve as a new treatment strategy for Alzheimer's disease.

  DOI：

  10.1021/jm201724m
• 作为产物：
  描述：

  3-amino-6-{4-[(4-methylpiperazin-1-yl)sulfonyl]phenyl}-N-pyridin-3-ylpyrazine-2-carboxamide hydrochloride 在 次磷酸 、 sodium nitrite 作用下， 以 水 为溶剂， 反应 16.0h， 以93%的产率得到6-{4-[(4-methylpiperazin-1-yl)sulfonyl]phenyl}-3-oxo-N-(pyridin-3-yl)-3,4-dihydropyrazine-2-carboxamide
  参考文献：
  名称：

  Discovery of Novel Potent and Highly Selective Glycogen Synthase Kinase-3β (GSK3β) Inhibitors for Alzheimer’s Disease: Design, Synthesis, and Characterization of Pyrazines

  摘要：

  Glycogen synthase kinase-3 beta, also called tau phosphorylating kinase, is a proline-directed serine/threonine kinase which was originally identified due to its role in glycogen metabolism. Active forms of GSK3 beta localize to pretangle pathology including dystrophic neuritis and neurofibrillary tangles in Alzheimer's disease (AD) brain. By using a high throughput screening (HTS) approach to search for new chemical series and cocrystallization of key analogues to guide the optimization and synthesis of our pyrazine series, we have developed highly potent and selective inhibitors showing cellular efficacy and blood-brain barrier penetrance. The inhibitors are suitable for in vivo efficacy testing and may serve as a new treatment strategy for Alzheimer's disease.

  DOI：

  10.1021/jm201724m