| 1304707-34-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• CAS: 1304707-34-3
• 化学式: C₁₇H₂₀N₄O
• 分子量: 296.372
• InChiKey: OCCOWLNJGHMAIJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.15
• 重原子数：
  22.0
• 可旋转键数：
  2.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  65.96
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  、 1-碘代丙烷 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以4%的产率得到
  参考文献：
  名称：

  Discovery of pyrrolo[2,3-d]pyrimidin-4-ones as corticotropin-releasing factor 1 receptor antagonists with a carbonyl-based hydrogen bonding acceptor

  摘要：

  A new class of pyrrolo[2,3-d]pyrimidin-4-one corticotropin-releasing factor 1 (CRF1) receptor antagonists has been designed and synthesized. In general, reported CRF1 receptor antagonists possess a sp(2)-nitrogen atom as hydrogen bonding acceptor (HBA) on their core scaffolds. We proposed to use a carbonyl group of pyrrolo[2,3-d]pyrimidin-4-one derivatives as a replacement for the sp(2)-nitrogen atom as HBA in classical CRF1 receptor antagonists. As a result, several pyrrolo[2,3-d]pyrimidin-4-one derivatives showed CRF1 receptor binding affinity with IC50 values in the submicromolar range. Ex vivo I-125-sauvagine binding studies showed that 2-(dipropylamino)-3,7-dimethyl-5-(2,4,6-trimethylphenyl)-3,7-dihydro-4H-pyrrolo [2,3-d]pyrimidin-4-one (16b) (30 mg/kg, po) was able to penetrate into the brain and inhibit radioligand binding to CRF1 receptors (frontal cortex, olfactory bulb, and pituitary) in mice. We identified pyrrolo[2,3-d] pyrimidin-4-one derivatives as the first CRF1 antagonists with a carbonyl-based HBA. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.02.086
• 作为产物：
  描述：

  2,4,6-三甲基苯基乙醛 在 三甲基溴硅烷 、 potassium carbonate 作用下， 以 二甲基亚砜 、 丙酮 、 乙腈 为溶剂， 生成
  参考文献：
  名称：

  Discovery of pyrrolo[2,3-d]pyrimidin-4-ones as corticotropin-releasing factor 1 receptor antagonists with a carbonyl-based hydrogen bonding acceptor

  摘要：

  A new class of pyrrolo[2,3-d]pyrimidin-4-one corticotropin-releasing factor 1 (CRF1) receptor antagonists has been designed and synthesized. In general, reported CRF1 receptor antagonists possess a sp(2)-nitrogen atom as hydrogen bonding acceptor (HBA) on their core scaffolds. We proposed to use a carbonyl group of pyrrolo[2,3-d]pyrimidin-4-one derivatives as a replacement for the sp(2)-nitrogen atom as HBA in classical CRF1 receptor antagonists. As a result, several pyrrolo[2,3-d]pyrimidin-4-one derivatives showed CRF1 receptor binding affinity with IC50 values in the submicromolar range. Ex vivo I-125-sauvagine binding studies showed that 2-(dipropylamino)-3,7-dimethyl-5-(2,4,6-trimethylphenyl)-3,7-dihydro-4H-pyrrolo [2,3-d]pyrimidin-4-one (16b) (30 mg/kg, po) was able to penetrate into the brain and inhibit radioligand binding to CRF1 receptors (frontal cortex, olfactory bulb, and pituitary) in mice. We identified pyrrolo[2,3-d] pyrimidin-4-one derivatives as the first CRF1 antagonists with a carbonyl-based HBA. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.02.086