[(7R)-4-(1,3-dimethylpyrazolo[3,4-d]pyrimidin-6-yl)-7-methyl-1,4-diazepan-1-yl]-[2-(triazol-2-yl)phenyl]methanone | 1607479-48-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: [(7R)-4-(1,3-dimethylpyrazolo[3,4-d]pyrimidin-6-yl)-7-methyl-1,4-diazepan-1-yl]-[2-(triazol-2-yl)phenyl]methanone
• CAS: 1607479-48-0
• 化学式: C₂₂H₂₅N₉O
• 分子量: 431.5
• InChiKey: YYZZNBPVRFCWEF-OAHLLOKOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  32
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  97.9
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  5 -氨基- 1,3-二甲基-4 -腈-1H -吡唑 在 ammonium hydroxide 、 乙腈 、 锌 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 15.5h， 生成 [(7R)-4-(1,3-dimethylpyrazolo[3,4-d]pyrimidin-6-yl)-7-methyl-1,4-diazepan-1-yl]-[2-(triazol-2-yl)phenyl]methanone
  参考文献：
  名称：

  Discovery of dual orexin receptor antagonists with rat sleep efficacy enabled by expansion of the acetonitrile-assisted/diphosgene-mediated 2,4-dichloropyrimidine synthesis

  摘要：

  Recent clinical studies have demonstrated that dual orexin receptor antagonists (OX1R and OX2R antagonists or DORAs) represent a novel treatment option for insomnia patients. Previously we have disclosed several compounds in the diazepane amide DORA series with excellent potency and both preclinical and clinical sleep efficacy. Additional SAR studies in this series were enabled by the expansion of the acetonitrile-assisted, diphosgene-mediated 2,4-dichloropyrimidine synthesis to novel substrates providing an array of Western heterocycles. These heterocycles were utilized to synthesize analogs in short order with high levels of potency on orexin 1 and orexin 2 receptors as well as in vivo sleep efficacy in the rat. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.03.052