2-Fluoro-8-[(4-phenyltriazol-1-yl)methyl]indolo[2,1-b]quinazoline-6,12-dione | 1384290-30-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 2-Fluoro-8-[(4-phenyltriazol-1-yl)methyl]indolo[2,1-b]quinazoline-6,12-dione
• CAS: 1384290-30-5
• 化学式: C₂₄H₁₄FN₅O₂
• 分子量: 423.406
• InChiKey: FMUYKFRRPHAARA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.38
• 重原子数：
  32.0
• 可旋转键数：
  3.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.04
• 拓扑面积：
  82.67
• 氢给体数：
  0.0
• 氢受体数：
  7.0

反应信息

• 作为产物：
  描述：

  苯,1-(叠氮甲基)-4-硝基- 在 盐酸 、 copper(l) iodide 、 硫酸 、 盐酸羟胺 、 铁粉 、 氯化铵 、 sodium sulfate 、 sodium ascorbate 、 三乙胺 作用下， 以 水 、 甲苯 、 乙腈 为溶剂， 生成 2-Fluoro-8-[(4-phenyltriazol-1-yl)methyl]indolo[2,1-b]quinazoline-6,12-dione
  参考文献：
  名称：

  Discovery of Tryptanthrin Derivatives as Potent Inhibitors of Indoleamine 2,3-Dioxygenase with Therapeutic Activity in Lewis Lung Cancer (LLC) Tumor-Bearing Mice

  摘要：

  Indoleamine 2,3-dioxygenase (IDO-1) is emerging as an important new therapeutic target for the treatment of cancer, neurological disorders, and other diseases that are characterized by pathological tryptophan metabolism. However, only a few structural classes are known to be IDO-1 inhibitors. In this study, a natural compound tryptanthrin was discovered to be a novel potent IDO-1 inhibitor by screening of indole-based structures. Three series of 13 tryptanthrin derivatives were synthesized, and the structure-activity analysis was undertaken. The optimization led to the identification of 5c, which exhibited the inhibitory activity at a nanomolar level. In vitro 5c dramatically augmented the proliferation of T cells. When administered to Lewis lung cancer (LLC) tumor-bearing mice, 5c significantly inhibited IDO-1 activity and suppressed tumor growth. In addition, 5c reduced the numbers of Fox3(+) regulatory T cells (Tregs), which are known to prevent the development of efficient antitumor immune responses.

  DOI：

  10.1021/jm401195n