3-(2,2,2-trifluoroethyl)imidazolidin-4-one | 1549264-32-5

• 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: 3-(2,2,2-trifluoroethyl)imidazolidin-4-one
• CAS: 1549264-32-5
• 化学式: C₅H₇F₃N₂O
• mdl: MFCD26027783
• 分子量: 168.119
• InChiKey: TUBMZICFMQBBGP-UHFFFAOYSA-N

物化性质

• 沸点：
  213.2±40.0 °C(Predicted)
• 密度：
  1.331±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  11
• 可旋转键数：
  1
• 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：
  5

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 、 3-(2,2,2-trifluoroethyl)imidazolidin-4-one 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 1-[2-(5-Chloro-6-methylthieno[2,3-d]pyrimidin-4-yl)sulfanylacetyl]-3-(2,2,2-trifluoroethyl)imidazolidin-4-one
  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