N-((1R,6R)-6-amino-2,2-difluorocyclohexyl)-5-methyl-4-(6-(1-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidin-3-yl)thiophene-2-carboxamide | 1109283-93-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡唑并嘧啶类
• 英文名称: N-((1R,6R)-6-amino-2,2-difluorocyclohexyl)-5-methyl-4-(6-(1-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidin-3-yl)thiophene-2-carboxamide
• 英文别名: N-[(1R,6R)-6-amino-2,2-difluorocyclohexyl]-5-methyl-4-[6-(1-methylpyrazol-4-yl)pyrazolo[1,5-a]pyrimidin-3-yl]thiophene-2-carboxamide
• CAS: 1109283-93-3
• 化学式: C₂₂H₂₃F₂N₇OS
• 分子量: 471.534
• InChiKey: SFILVHFYISPBOI-IEBWSBKVSA-N

物化性质

• 溶解度：
  溶于二甲基亚砜

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  33
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  131
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  methyl 5-methyl-4-(6-(1-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidin-3-yl)thiophene-2-carboxylate 在 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 、 potassium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 生成 N-((1R,6R)-6-amino-2,2-difluorocyclohexyl)-5-methyl-4-(6-(1-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidin-3-yl)thiophene-2-carboxamide
  参考文献：
  名称：

  Optimization of microtubule affinity regulating kinase (MARK) inhibitors with improved physical properties

  摘要：

  Inhibition of microtubule affinity regulating kinase (MARK) represents a potentially attractive means of arresting neurofibrillary tangle pathology in Alzheimer's disease. This manuscript outlines efforts to optimize a pyrazolopyrimidine series of MARK inhibitors by focusing on improvements in potency, physical properties and attributes amenable to CNS penetration. A unique cylcyclohexyldiamine scaffold was identified that led to remarkable improvements in potency, opening up opportunities to reduce MW, Pgp efflux and improve pharmacokinetic properties while also conferring improved solubility. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2016.02.003

文献信息

• PYRAZOLO[1,5-a]PYRIMIDINE DERIVATIVES
  申请人：Stanton Matthew G.

  公开号：US20100305091A1

  公开（公告）日：2010-12-02

  Compounds of the following formula (I) are inhibitors of microtubule affinity regulating kinase, and hence find use in the treatment of neurodegenerative diseases associated with hyperphosphorylation of tau.

  以下公式（I）的化合物是微管亲和力调节激酶的抑制剂，因此可用于治疗与tau超磷酸化相关的神经退行性疾病。
• US8461162B2
  申请人：——

  公开号：US8461162B2

  公开（公告）日：2013-06-11