N,N'-bis-(2-ethoxyethyl)urea | 22033-17-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机碳酸及其衍生物
• 英文名称: N,N'-bis-(2-ethoxyethyl)urea
• 英文别名: 1,3-Bis(2-ethoxyethyl)urea
• CAS: 22033-17-6
• 化学式: C₉H₂₀N₂O₃
• mdl: MFCD24390993
• 分子量: 204.269
• InChiKey: SVNFQJXDHUSRIO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  14
• 可旋转键数：
  8
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.888
• 拓扑面积：
  59.6
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  丙二酸 、 N,N'-bis-(2-ethoxyethyl)urea 在 乙酸酐 、 溶剂黄146 作用下， 反应 4.5h， 生成 1,3-bis(2-ethoxyethyl)pyrimidine-2,4,6(1H,3H,5H)-trione
  参考文献：
  名称：

  Pyrimidine-2,4,6-trione Derivatives and Their Inhibition of Mutant SOD1-Dependent Protein Aggregation. Toward a Treatment for Amyotrophic Lateral Sclerosis

  摘要：

  Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive loss of motor neurons, leading to muscle weakness, paralysis, and death, most often from respiratory failure. The only FDA-approved drug for the treatment of ALS, riluzole, only extends the median survival in patients by 2-3 months. There is an urgent need for novel therapeutic strategies for this devastating disease. Using a high-throughput screening assay targeting an ALS cultured cell model (PC12-G93A-YFP cell line), we previously identified three chemotypes that were neuroprotective. We present a further detailed analysis of one promising scaffold from that group, pyrimidine-2,4,6-triones (PYTs), characterizing a number of PYT analogues using SAR and ADME. The PYT compounds show good potency, superior ADME data, low toxicity, brain penetration, and excellent oral bioavailability. Compounds from this series show 100% efficacy in the protection assay with a good correlation in activity between the protection and protein aggregation assays. The modifications of the PYT scaffold presented here suggest that this chemical structure may be a novel drug candidate scaffold for use in clinical trials in ALS.

  DOI：

  10.1021/jm101549k
• 作为产物：
  描述：

  荒酸二甲酯 、 2-乙氧基乙胺 以 甲醇 为溶剂， 反应 24.0h， 生成 N,N'-bis-(2-ethoxyethyl)urea
  参考文献：
  名称：

  Pyrimidine-2,4,6-trione Derivatives and Their Inhibition of Mutant SOD1-Dependent Protein Aggregation. Toward a Treatment for Amyotrophic Lateral Sclerosis

  摘要：

  Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive loss of motor neurons, leading to muscle weakness, paralysis, and death, most often from respiratory failure. The only FDA-approved drug for the treatment of ALS, riluzole, only extends the median survival in patients by 2-3 months. There is an urgent need for novel therapeutic strategies for this devastating disease. Using a high-throughput screening assay targeting an ALS cultured cell model (PC12-G93A-YFP cell line), we previously identified three chemotypes that were neuroprotective. We present a further detailed analysis of one promising scaffold from that group, pyrimidine-2,4,6-triones (PYTs), characterizing a number of PYT analogues using SAR and ADME. The PYT compounds show good potency, superior ADME data, low toxicity, brain penetration, and excellent oral bioavailability. Compounds from this series show 100% efficacy in the protection assay with a good correlation in activity between the protection and protein aggregation assays. The modifications of the PYT scaffold presented here suggest that this chemical structure may be a novel drug candidate scaffold for use in clinical trials in ALS.

  DOI：

  10.1021/jm101549k

文献信息

• US4059665A
  申请人：——

  公开号：US4059665A

  公开（公告）日：1977-11-22
• US4103093A
  申请人：——

  公开号：US4103093A

  公开（公告）日：1978-07-25
• US4158736A
  申请人：——

  公开号：US4158736A

  公开（公告）日：1979-06-19
• US4180631A
  申请人：——

  公开号：US4180631A

  公开（公告）日：1979-12-25
• US4246370A
  申请人：——

  公开号：US4246370A

  公开（公告）日：1981-01-20