3-(1H-indol-3-yl)-4-(5-piperazin-1-yl-2-trifluoromethylphenyl)pyrrole-2,5-dione | 1260181-10-9

• 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: 3-(1H-indol-3-yl)-4-(5-piperazin-1-yl-2-trifluoromethylphenyl)pyrrole-2,5-dione
• 英文别名: 3-(1H-Indol-3-yl)-4-(5-piperazin-1-yl-2-trifluoromethyl-phenyl)-pyrrole-2,5-dione；3-(1H-indol-3-yl)-4-[5-piperazin-1-yl-2-(trifluoromethyl)phenyl]pyrrole-2,5-dione
• CAS: 1260181-10-9
• 化学式: C₂₃H₁₉F₃N₄O₂
• 分子量: 440.425
• InChiKey: KSWPVLJUULLKJR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  32
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  77.2
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  3-(1H-indol-3-yl)-4-(5-piperazin-1-yl-2-trifluoromethylphenyl)pyrrole-2,5-dione 在 4-二甲氨基吡啶 、 sodium methylate 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 2.5h， 生成 3-[5-[4-(2-羟基-2-甲基-1-氧丙基)-1-哌嗪基]-2-(三氟甲基)苯基]-4-(1H-吲哚-3-基)-1H-吡咯-2,5-二酮
  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
• 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 3-(1H-indol-3-yl)-4-(5-piperazin-1-yl-2-trifluoromethylphenyl)pyrrole-2,5-dione
  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

• [EN] JAK3 SELECTIVE INHIBITOR<br/>[FR] INHIBITEUR SÉLECTIF DE JAK3<br/>[ZH] 一种JAK3选择性抑制剂
  申请人：UNIV PEKING SHENZHEN GRADUATE SCHOOL

  公开号：WO2019228442A1

  公开（公告）日：2019-12-05

  本发明涉及一种式(I)/(II)化合物或其药学上可接受的盐。式(I)中，Rh、Rg、Rf、m、Re、Rd、Ra、Rb和Rc如说明书中所定义。本发明还涉及一种包括上述式(I)/(II)化合物或其药学上可接受的盐的药物组合物，以及上述式(I)/(II)化合物或上述药物组合物在制备用于治疗炎症如类风湿关节炎的药物中的用途。