4-(pyrrolidin-1-ylmethyl)pyridin-3-amine | 486422-82-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 4-(pyrrolidin-1-ylmethyl)pyridin-3-amine
• CAS: 486422-82-6
• 化学式: C₁₀H₁₅N₃
• 分子量: 177.249
• InChiKey: HMZLOEZULSYZQU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  42.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-氨基-6-溴吡嗪-2-甲酸 、 4-(pyrrolidin-1-ylmethyl)pyridin-3-amine 在 O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium tetrafluoroborate 、 1-hydroxy-1H-benzotriazol hydrate 、 N,N-二异丙基乙胺 作用下， 以 乙腈 为溶剂， 反应 12.0h， 以98%的产率得到3-amino-6-bromo-N-[4-(pyrrolidin-1-ylmethyl)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：

  (4-甲酰基吡啶-3-基)氨基甲酸叔丁酯 在 溶剂黄146 、 三氟乙酸 作用下， 以 二氯甲烷 、 1,2-二氯乙烷 为溶剂， 反应 11.5h， 生成 4-(pyrrolidin-1-ylmethyl)pyridin-3-amine
  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。
• GSK-3 inhibitors
  申请人：BRISTOL-MYERS SQUIBB COMPANY

  公开号：US10752609B2

  公开（公告）日：2020-08-25

  The disclosure generally relates to compounds of formula I, including their salts, as well as compositions and methods of using the compounds to treat disorders associated with GSK-3.

  本公开内容一般涉及式 I 的化合物，包括它们的盐类，以及使用这些化合物治疗与 GSK-3 相关疾病的组合物和方法。
• 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
• GSK-3 INHIBITORS
  申请人：Bristol-Myers Squibb Company

  公开号：EP3544613A1

  公开（公告）日：2019-10-02
• [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).