methyl 2-(ethoxymethylidene)-4,4,4-trifluoro-3-oxobutanoate | 239463-92-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 酮酸及其衍生物
• 英文名称: methyl 2-(ethoxymethylidene)-4,4,4-trifluoro-3-oxobutanoate
• 英文别名: Methyl 2-(ethoxymethylene)-4,4,4-trifluoro-3-oxobutanoate
• CAS: 239463-92-4
• 化学式: C₈H₉F₃O₄
• 分子量: 226.152
• InChiKey: KLFDOMKMXLDIFI-UHFFFAOYSA-N

物化性质

• 沸点：
  190.5±40.0 °C(Predicted)
• 密度：
  1.275±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  15
• 可旋转键数：
  5
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  methyl 2-(ethoxymethylidene)-4,4,4-trifluoro-3-oxobutanoate 在 甲基肼 作用下， 以 四氢呋喃 为溶剂， 反应 2.25h， 以70%的产率得到1-(1-methyl-3-(trifluoromethyl)-1H-pyrazol-4-yl)ethanone
  参考文献：
  名称：

  Lead Optimization toward Proof-of-Concept Tools for Huntington’s Disease within a 4-(1H-Pyrazol-4-yl)pyrimidine Class of Pan-JNK Inhibitors

  摘要：

  Through medicinal chemistry lead optimization studies focused on calculated properties and guided by X-ray crystallography and computational modeling, potent pan-JNK inhibitors were identified that showed submicromolar activity in a cellular assay. Using in vitro ADME profiling data, 9t was identified as possessing favorable permeability and a low potential for efflux, but it was rapidly cleared in liver microsomal incubations. In a mouse pharmacokinetics study, compound 9t was brain-penetrant after oral dosing, but exposure was limited by high plasma clearance. Brain exposure at a level expected to support modulation of a pharmacodynamic marker in mouse was achieved when the compound was coadministered with the pan-cytochrome P450 inhibitor 1-aminobenzotriazole.

  DOI：

  10.1021/jm5013598
• 作为产物：
  描述：

  三氟乙酰丙酮 、 原甲酸三乙酯 在 乙酸酐 作用下， 反应 19.0h， 以35%的产率得到methyl 2-(ethoxymethylidene)-4,4,4-trifluoro-3-oxobutanoate
  参考文献：
  名称：

  Lead Optimization toward Proof-of-Concept Tools for Huntington’s Disease within a 4-(1H-Pyrazol-4-yl)pyrimidine Class of Pan-JNK Inhibitors

  摘要：

  Through medicinal chemistry lead optimization studies focused on calculated properties and guided by X-ray crystallography and computational modeling, potent pan-JNK inhibitors were identified that showed submicromolar activity in a cellular assay. Using in vitro ADME profiling data, 9t was identified as possessing favorable permeability and a low potential for efflux, but it was rapidly cleared in liver microsomal incubations. In a mouse pharmacokinetics study, compound 9t was brain-penetrant after oral dosing, but exposure was limited by high plasma clearance. Brain exposure at a level expected to support modulation of a pharmacodynamic marker in mouse was achieved when the compound was coadministered with the pan-cytochrome P450 inhibitor 1-aminobenzotriazole.

  DOI：

  10.1021/jm5013598