1-methyl-1H-pyrrolo[3,2-b]quinoline-3-carbaldehyde | 1603830-19-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 1-methyl-1H-pyrrolo[3,2-b]quinoline-3-carbaldehyde
• CAS: 1603830-19-8
• 化学式: C₁₃H₁₀N₂O
• 分子量: 210.235
• InChiKey: HLSJUAKSAZFOQZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.54
• 重原子数：
  16.0
• 可旋转键数：
  1.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  34.89
• 氢给体数：
  0.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  1-methyl-1H-pyrrolo[3,2-b]quinoline-3-carbaldehyde 在 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 potassium tert-butylate 、 sodium carbonate 、 caesium carbonate 、 9-硼双环[3.3.1]壬烷 作用下， 以 四氢呋喃 、 水 、 二甲基亚砜 为溶剂， 反应 48.0h， 生成 1-methyl-3-(2-{[3-(pyrimidin-5-yl)pyrazin-2-yl]oxy}ethyl)-1H-pyrrolo[3,2-b]quinoline
  参考文献：
  名称：

  Design, synthesis and pharmacological evaluation of novel polycyclic heteroarene ethers as PDE10A inhibitors: Part I

  摘要：

  We report analogue-based rational design and synthesis of two novel series of polycyclic heteroarenes, pyrrolo[3,2-b]quinolines and pyrido[2,3-b]indoles, tethered to a biaryl system by a methyl-, ethyl-or propyl ether as PDE10A inhibitors. A number of analogues were prepared with variable chain length and evaluated for their ability to block PDE10A enzyme using a radiometric assay. Detailed SAR analyses revealed that compounds with an ethyl ether linker are superior in potency compared to compounds with methyl or propyl ether linkers. These compounds, in general, showed poor metabolic stability in rat and human liver microsomes. The metabolic profile of one of the potent compounds was studied in detail to identify metabolic liabilities of these compounds. Structural modifications were carried out that resulted in improved metabolic stability without significant loss of potency. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.03.054
• 作为产物：
  描述：

  邻硝基苯甲醛 在 吡啶 、 4-二甲氨基吡啶 、 manganese(IV) oxide 、 sodium tetrahydroborate 、 palladium 10% on activated carbon 、 氢气 、 potassium carbonate 、 三氯氧磷 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 90.0 ℃ 、413.7 kPa 条件下， 反应 72.5h， 生成 1-methyl-1H-pyrrolo[3,2-b]quinoline-3-carbaldehyde
  参考文献：
  名称：

  Design, synthesis and pharmacological evaluation of novel polycyclic heteroarene ethers as PDE10A inhibitors: Part I

  摘要：

  We report analogue-based rational design and synthesis of two novel series of polycyclic heteroarenes, pyrrolo[3,2-b]quinolines and pyrido[2,3-b]indoles, tethered to a biaryl system by a methyl-, ethyl-or propyl ether as PDE10A inhibitors. A number of analogues were prepared with variable chain length and evaluated for their ability to block PDE10A enzyme using a radiometric assay. Detailed SAR analyses revealed that compounds with an ethyl ether linker are superior in potency compared to compounds with methyl or propyl ether linkers. These compounds, in general, showed poor metabolic stability in rat and human liver microsomes. The metabolic profile of one of the potent compounds was studied in detail to identify metabolic liabilities of these compounds. Structural modifications were carried out that resulted in improved metabolic stability without significant loss of potency. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.03.054