3-amino-6-[2-fluoro-4-(4-methylpiperazin-1-yl)sulfonyl-phenyl]-N-pyridin-3-yl-pyrazine-2-carboxamide | 486424-43-5

• 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-6-[2-fluoro-4-(4-methylpiperazin-1-yl)sulfonyl-phenyl]-N-pyridin-3-yl-pyrazine-2-carboxamide
• 英文别名: 3-Amino-6-[2-fluoro-4-[(4-methyl-1-piperazinyl)sulfonyl]phenyl]-N-3-pyridinyl-2-pyrazinecarboxamide；3-amino-6-[2-fluoro-4-(4-methylpiperazin-1-yl)sulfonylphenyl]-N-pyridin-3-ylpyrazine-2-carboxamide
• CAS: 486424-43-5
• 化学式: C₂₁H₂₂FN₇O₃S
• 分子量: 471.515
• InChiKey: FANYLTZIIIZQJA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  33
• 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：
  143
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  3-amino-6-[2-fluoro-4-(4-methylpiperazin-1-yl)sulfonyl-phenyl]-N-pyridin-3-yl-pyrazine-2-carboxamide 在 盐酸 作用下， 以 乙醚 、 二氯甲烷 为溶剂， 以28%的产率得到3-amino-6-{2-fluoro-4-[(4-methylpiperazin-1-yl)sulfonyl]phenyl}-N-pyridin-3-ylpyrazine-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：

  4-(acetylamino)-3-fluorobenzenesulfonyl fluoride 在 盐酸 、 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 、 氢溴酸 、 sodium carbonate 、 三乙胺 、 sodium nitrite 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 172.83h， 生成 3-amino-6-[2-fluoro-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

文献信息

• Use
  申请人：Bhat Ratan

  公开号：US20070213322A1

  公开（公告）日：2007-09-13

  The present invention relates to a new use of a compound of the formula (I) wherein R 1 is NH 2 , piperazin-1-yl, 4-methylpiperazin-1-yl, 4-methyl-1,4-diazepan-1-yl or 4-ethylpiperazin-1-yl; R 2 is hydrogen, fluoro, CH 3 , CH 2 CH 3 , OCH 3 , CF 3 or OCF 3 ; R 3 is hydrogen, CH 3 or fluoro; as a free base or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for the prevention and/or treatment of bone-related disorders, osteoporosis and increasing bone formation, bone mineral density. The present invention further relates to a method of prevention and/or treatment of these disorders.
• US7576093B2
  申请人：——

  公开号：US7576093B2

  公开（公告）日：2009-08-18
• Discovery of Novel Potent and Highly Selective Glycogen Synthase Kinase-3β (GSK3β) Inhibitors for Alzheimer’s Disease: Design, Synthesis, and Characterization of Pyrazines
  作者：Stefan Berg、Margareta Bergh、Sven Hellberg、Katharina Högdin、Yvonne Lo-Alfredsson、Peter Söderman、Stefan von Berg、Tatjana Weigelt、Mats Ormö、Yafeng Xue、Julie Tucker、Jan Neelissen、Eva Jerning、Yvonne Nilsson、Ratan Bhat

  DOI：10.1021/jm201724m

  日期：2012.11.8

  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.