3-amino-6-bromo-N-{4-[(dimethylamino)methyl]pyridin-3-yl}pyrazine-2-carboxamide | 486423-03-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 3-amino-6-bromo-N-{4-[(dimethylamino)methyl]pyridin-3-yl}pyrazine-2-carboxamide
• 英文别名: 3-amino-6-bromo-N-[4-[(dimethylamino)methyl]pyridin-3-yl]pyrazine-2-carboxamide
• CAS: 486423-03-4
• 化学式: C₁₃H₁₅BrN₆O
• 分子量: 351.206
• InChiKey: SECPSOVFXFXLJL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  97
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-(磺酰吡咯啉)苯基硼酸 、 3-amino-6-bromo-N-{4-[(dimethylamino)methyl]pyridin-3-yl}pyrazine-2-carboxamide 在 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 sodium carbonate 、 四(三苯基膦)钯 、 lithium chloride 、 盐酸 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 二氯甲烷 为溶剂， 反应 12.0h， 以10%的产率得到3-amino-N-{4-[(dimethylamino)methyl]pyridin-3-yl}-6-[4-(pyrrolidin-1-ylsulfonyl)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：

  (4-甲酰基吡啶-3-基)氨基甲酸叔丁酯 在 O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium tetrafluoroborate 、 1-hydroxy-1H-benzotriazol hydrate 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 15.5h， 生成 3-amino-6-bromo-N-{4-[(dimethylamino)methyl]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

• Arylamines for the treatment of conditions associated with gsk-3
  申请人：Berg Stefan

  公开号：US20060052396A1

  公开（公告）日：2006-03-09

  The present invention relates to new compounds of formula (I) wherein Z, Y, X, P, Q, R, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , A, m and n are defined as in any one of claims 1 to 3, a process for their preparation and new intermediates prepared therein, pharmaceutical formulations containing said therapeutically active compounds and to the use of said active compounds for the treatment of conditions associated with glycogens synthase kinase-3 (GSK3).

  本发明涉及具有公式（I）的新化合物，其中Z、Y、X、P、Q、R、R1、R2、R3、R4、R5、R6、R7、R8、R9、R10、R11、R12、A、m和n的定义如权利要求1至3中的任意一项，以及制备它们的过程和其中制备的新中间体，含有所述治疗活性化合物的制药配方以及使用所述活性化合物治疗与糖原合酶激酶-3（GSK3）相关的疾病的方法。
• ARYLAMINES FOR THE TREATMENT OF CONDITIONS ASSOCIATED WITH GSK-3
  申请人：AstraZeneca AB

  公开号：EP1414801A1

  公开（公告）日：2004-05-06
• [EN] ARYLAMINES FOR THE TREATMENT OF CONDITIONS ASSOCIATED WITH GSK-3<br/>[FR] NOUVEAUX COMPOSES
  申请人：ASTRAZENECA AB

  公开号：WO2003004472A1

  公开（公告）日：2003-01-16

  The present invention relates to new compounds of formula (I) wherein Z, Y, X, P, Q, R, R?1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, R12¿, A, m and n are defined as in any one of claims 1 to 3, a process for their preparation and new intermediates prepared therein, pharmaceutical formulations containing said therapeutically active compounds and to the use of said active compounds for the treatment of conditions associated with glycogens synthase kinase-3 (GSK3).
• 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.