1,4-dimethyl-5-imidazolidinone | 82044-01-7

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 1,4-dimethyl-5-imidazolidinone
• 英文别名: 3,5-dimethylimidazolidin-4-one
• CAS: 82044-01-7
• 化学式: C₅H₁₀N₂O
• 分子量: 114.147
• InChiKey: VPZBJFGUILDYED-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 重原子数：
  8
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  32.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-((5-chloro-6-methylthieno[2,3-d]pyrimidin-4-yl)thio)acetic acid 、 1,4-dimethyl-5-imidazolidinone 在 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.25h， 生成
  参考文献：
  名称：

  Scaffold-hopping identifies furano[2,3-d]pyrimidine amides as potent Notum inhibitors

  摘要：

  The carboxylesterase Notum is a key negative regulator of the Wnt signaling pathway by mediating the depalmitoleoylation of Wnt proteins. Our objective was to discover potent small molecule inhibitors of Notum suitable for exploring the regulation of Wnt signaling in the central nervous system. Scaffold-hopping from thienopyrimidine acids 1 and 2, supported by X-ray structure determination, identified 3-methylimidazolin-4-one amides 20-24 as potent inhibitors of Notum with activity across three orthogonal assay formats (biochemical, extra-cellular, occupancy). A preferred example 24 demonstrated good stability in mouse microsomes and plasma, and cell permeability in the MDCK-MDR1 assay albeit with modest P-gp mediated efflux. Pharmacokinetic studies with 24 were performed in vivo in mouse with single oral administration of 24 showing good plasma exposure and reasonable CNS penetration. We propose that 24 is a new chemical tool suitable for cellular studies to explore the fundamental biology of Notum.

  DOI：

  10.1016/j.bmcl.2019.126751
• 作为产物：
  描述：

  5,6-二氢-1,3,5,5-四甲基-2(1H)-吡嗪酮 以 水 为溶剂， 反应 96.0h， 以58%的产率得到1,4-dimethyl-5-imidazolidinone
  参考文献：
  名称：

  A photochemical ring contraction of an imino lactam

  摘要：

  DOI：

  10.1021/jo00137a022

文献信息

• KLEYER, D. L.;KOCH, T. H., J. ORG. CHEM., 1982, 47, N 16, 3145-3148
  作者：KLEYER, D. L.、KOCH, T. H.

  DOI：——

  日期：——
• Scaffold-hopping identifies furano[2,3-d]pyrimidine amides as potent Notum inhibitors
  作者：Benjamin N. Atkinson、David Steadman、William Mahy、Yuguang Zhao、James Sipthorp、Elliott D. Bayle、Fredrik Svensson、George Papageorgiou、Fiona Jeganathan、Sarah Frew、Amy Monaghan、Magda Bictash、E. Yvonne Jones、Paul V. Fish

  DOI：10.1016/j.bmcl.2019.126751

  日期：2020.2

  The carboxylesterase Notum is a key negative regulator of the Wnt signaling pathway by mediating the depalmitoleoylation of Wnt proteins. Our objective was to discover potent small molecule inhibitors of Notum suitable for exploring the regulation of Wnt signaling in the central nervous system. Scaffold-hopping from thienopyrimidine acids 1 and 2, supported by X-ray structure determination, identified 3-methylimidazolin-4-one amides 20-24 as potent inhibitors of Notum with activity across three orthogonal assay formats (biochemical, extra-cellular, occupancy). A preferred example 24 demonstrated good stability in mouse microsomes and plasma, and cell permeability in the MDCK-MDR1 assay albeit with modest P-gp mediated efflux. Pharmacokinetic studies with 24 were performed in vivo in mouse with single oral administration of 24 showing good plasma exposure and reasonable CNS penetration. We propose that 24 is a new chemical tool suitable for cellular studies to explore the fundamental biology of Notum.
• A photochemical ring contraction of an imino lactam
  作者：Don L. Kleyer、Tad H. Koch

  DOI：10.1021/jo00137a022

  日期：1982.7