4-{3-[4-(1H-indol-3-yl)-2,5-dioxo-2,5-dihydro-1H-pyrrol-3-yl]-4-trifluoromethylphenyl}piperazine-1-carbaldehyde | 1260181-12-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 4-{3-[4-(1H-indol-3-yl)-2,5-dioxo-2,5-dihydro-1H-pyrrol-3-yl]-4-trifluoromethylphenyl}piperazine-1-carbaldehyde
• 英文别名: 4-{3-[4-(1H-Indol-3-yl)-2,5-dioxo-2,5-dihydro-1H-pyrrol-3-yl]-4-trifluoromethyl-phenyl}-piperazine-1-carbaldehyde；4-[3-[4-(1H-indol-3-yl)-2,5-dioxopyrrol-3-yl]-4-(trifluoromethyl)phenyl]piperazine-1-carbaldehyde
• CAS: 1260181-12-1
• 化学式: C₂₄H₁₉F₃N₄O₃
• 分子量: 468.435
• InChiKey: IKLXBNGCTJXQCF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  34
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  85.5
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  5-氟-2-(三氟甲基)苯乙酸 在 potassium tert-butylate 、 N,N'-羰基二咪唑 作用下， 以 四氢呋喃 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 4-{3-[4-(1H-indol-3-yl)-2,5-dioxo-2,5-dihydro-1H-pyrrol-3-yl]-4-trifluoromethylphenyl}piperazine-1-carbaldehyde
  参考文献：
  名称：

  Identification of a Potent Janus Kinase 3 Inhibitor with High Selectivity within the Janus Kinase Family

  摘要：

  We describe a synthetic approach toward the rapid modification of phenyl-indolyl maleimides and the discovery of potent Jak3 inhibitor 1 with high selectivity within the Jak kinase family We provide a rationale for this unprecedented selectivity based on the X-ray crystal structure of an analogue of 1 bound to the ATP-binding site of Jak3 While equally potent compared to the Pfizer pan Jak inhibitor CP-690,550 (2) in an enzymatic Jak3 assay, compound 1 was found to be 20 fold less potent in cellular assays measuring cytokine-triggered signaling through cytokine receptors containing the common gamma chain (gamma C) Contrary to compound 1, compound 2 inhibited Jak1 in addition to Jak3 Permeability and cellular concentrations of compounds 1 and 2 were similar As Jak3 always cooperates with Jak 1 for signaling, we speculate that specific inhibition of Jak3 is not sufficient to efficiently block gamma C cytokine signal transduction required for strong immunosuppression

  DOI：

  10.1021/jm101157q

文献信息

• Identification of a Potent Janus Kinase 3 Inhibitor with High Selectivity within the Janus Kinase Family
  作者：Gebhard Thoma、Francois Nuninger、Rocco Falchetto、Erwin Hermes、Gisele A. Tavares、Eric Vangrevelinghe、Hans-Günter Zerwes

  DOI：10.1021/jm101157q

  日期：2011.1.13

  We describe a synthetic approach toward the rapid modification of phenyl-indolyl maleimides and the discovery of potent Jak3 inhibitor 1 with high selectivity within the Jak kinase family We provide a rationale for this unprecedented selectivity based on the X-ray crystal structure of an analogue of 1 bound to the ATP-binding site of Jak3 While equally potent compared to the Pfizer pan Jak inhibitor CP-690,550 (2) in an enzymatic Jak3 assay, compound 1 was found to be 20 fold less potent in cellular assays measuring cytokine-triggered signaling through cytokine receptors containing the common gamma chain (gamma C) Contrary to compound 1, compound 2 inhibited Jak1 in addition to Jak3 Permeability and cellular concentrations of compounds 1 and 2 were similar As Jak3 always cooperates with Jak 1 for signaling, we speculate that specific inhibition of Jak3 is not sufficient to efficiently block gamma C cytokine signal transduction required for strong immunosuppression