3-amino-N-(2-methoxyphenyl)-6-{4-[(4-methylpiperazin-1-yl)sulfonyl]phenyl}pyrazine-2-carboxamide hydrochloride | 714237-16-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3-amino-N-(2-methoxyphenyl)-6-{4-[(4-methylpiperazin-1-yl)sulfonyl]phenyl}pyrazine-2-carboxamide hydrochloride
• 英文别名: 3-amino-N-(2-methoxyphenyl)-6-[4-(4-methylpiperazin-1-yl)sulfonylphenyl]pyrazine-2-carboxamide;hydrochloride
• CAS: 714237-16-8
• 化学式: C₂₃H₂₆N₆O₄S*ClH
• 分子量: 519.024
• InChiKey: SVPLOFWIYAQXHH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.34
• 重原子数：
  35
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  139
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  3-amino-N-(2-methoxyphenyl)-6-{4-[(4-methylpiperazin-1-yl)sulfonyl]phenyl}pyrazine-2-carboxamide hydrochloride 、 甲氧苯胺 在 1-hydroxy-1H-benzotriazol hydrate 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 、 盐酸 作用下， 以 N,N-二甲基甲酰胺 、 乙醚 、 二氯甲烷 为溶剂， 以62%的产率得到3-amino-N-(4-methoxyphenyl)-6-{4-[(4-methylpiperazin-1-yl)sulfonyl]phenyl}pyrazine-2-carboxamide hydrochloride
  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：

  1-(4-溴苯基磺酰基)-4-甲基哌嗪 在 正丁基锂 、 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 1-hydroxy-1H-benzotriazol hydrate 、 水 、 silica gel 、 sodium carbonate 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 、 lithium hydroxide 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 21.5h， 生成 3-amino-N-(2-methoxyphenyl)-6-{4-[(4-methylpiperazin-1-yl)sulfonyl]phenyl}pyrazine-2-carboxamide hydrochloride
  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

文献信息

• [EN] NOBEL COMPOUNDS HAVING SELECTIVE INHIBITING EFFECT AT GSK3<br/>[FR] NOUVEAUX COMPOSES PRESENTANT UN EFFET INHIBITEUR SELECTIF DE LA GSK3
  申请人：ASTRAZENECA AB

  公开号：WO2004055006A1

  公开（公告）日：2004-07-01

  The present invention relates to new compounds, a process for their preparation and new intermediates used therein, pharmaceutical formulations containing said therapeutically active compounds and to the use of said active compounds in therapy, such as provide compounds having a selective inhibiting effect at GSK3.

  本发明涉及新化合物，其制备方法和其中使用的新中间体，包含上述治疗活性化合物的药物配方，以及该活性化合合物在治疗中的应用，例如提供具有对GSK3具有选择性抑制作用的化合物。
• Nobel compounds having selective inhibiting effect at gsk3
  申请人：Berg Stefan

  公开号：US20060173014A1

  公开（公告）日：2006-08-03

  The present invention relates to new compounds, a process for their preparation and new intermediates used therein, pharmaceutical formulations containing said therapeutically active compounds and to the use of said active compounds in therapy, such as provide compounds having a selective inhibiting effect at GSK3.

  本发明涉及新化合物、其制备方法和所使用的新中间体，包括含有上述治疗活性化合物的药物配方，以及上述活性化合物在治疗中的用途，提供具有选择性抑制GSK3作用的化合物。
• Novel Compounds Having Selective Inhibiting Effect at GSK3
  申请人：Berg Stefan

  公开号：US20100081660A1

  公开（公告）日：2010-04-01

  The present invention relates to new compounds, a process for their preparation and new intermediates used therein, pharmaceutical formulations containing said therapeutically active compounds and to the use of said active compounds in therapy, such as provide compounds having a selective inhibiting effect at GSK3.

  本发明涉及新化合物、其制备方法和其中使用的新中间体、含有所述治疗活性化合物的药物制剂以及所述活性化合物在治疗中的使用，例如提供具有选择性抑制GSK3效应的化合物。
• Compounds having selective inhibiting effect at GSK3
  申请人：AstraZeneca AB

  公开号：US07595319B2

  公开（公告）日：2009-09-29

  Selective phenyl substituted aminopyrazine inhibitors of GSK3 useful for the prevention and/or treatment of cognitive disorders.

  选择性苯基取代氨基吡嗪GSK3抑制剂，用于预防和/或治疗认知障碍。
• NOVEL COMPOUNDS HAVING SELECTIVE INHIBITING EFFECT AT GSK3
  申请人：AstraZeneca AB

  公开号：EP1575939A1

  公开（公告）日：2005-09-21