4-azido-2-chloro-1-(trifluoromethyl)benzene | 1146219-88-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-azido-2-chloro-1-(trifluoromethyl)benzene
• CAS: 1146219-88-6
• 化学式: C₇H₃ClF₃N₃
• 分子量: 221.569
• InChiKey: JBOXOEVWFNKCJB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  14.0
• 可旋转键数：
  1.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  48.76
• 氢给体数：
  0.0
• 氢受体数：
  1.0

反应信息

• 作为反应物：
  描述：

  4-azido-2-chloro-1-(trifluoromethyl)benzene 、 N,N-dimethyl o-nitrostyrene amine 以 乙腈 为溶剂， 反应 48.0h， 生成 1-(3-chloro-4-(trifluoromethyl)phenyl)-4-(2-nitrophenyl)-1H-1,2,3-triazole
  参考文献：
  名称：

  (1,2,3-Triazol-4-yl)benzenamines: Synthesis and activity against VEGF receptors 1 and 2

  摘要：

  Derivatives of (1,2,3-triazol-4-yl) benzenamines are described as potent and ATP-competitive inhibitors of vascular endothelial growth factor receptors I and II (VEGFR-1/2). A number of compounds exhibited VEGFR-2 and VEGFR-1 inhibitory activity comparable to that of Vatalanib (TM) in both HTRF enzymatic and cellular assays. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.01.046
• 作为产物：
  描述：

  4-氨基-2-氯三氟甲苯 在 三氟乙酸 、 sodium nitrite 、 sodium azide 作用下， 以 水 为溶剂， 反应 3.5h， 生成 4-azido-2-chloro-1-(trifluoromethyl)benzene
  参考文献：
  名称：

  通过优化晶体片段命中，设计一种有效的、选择性的、脑渗透性 Wnt 失活酶 Notum 抑制剂

  摘要：

  Notum 是一种羧酸酯酶，可通过 Wnt 蛋白上必需的棕榈油酸酯基团的脱酰化来抑制 Wnt 信号传导。人们越来越了解 Notum 在结直肠癌和阿尔茨海默氏病等人类疾病中所起的作用，支持发现改进的抑制剂的需要，特别是用于神经退行性疾病模型的抑制剂。在这里，我们描述了8l (ARUK3001185) 的发现和概况，它是一种有效的、选择性的、脑渗透性的 Notum 活性抑制剂，适合在啮齿动物疾病模型中口服给药。对 Diamond-SGC Poied 文库进行与 Notum 结合的晶体片段筛选，并通过生化酶测定对抑制活性进行排序，将6a和6b鉴定为一对出色的命中结果。 6的片段开发产生了8l ，在基于细胞的报告基因测定中，在 Notum 存在的情况下恢复了 Wnt 信号传导。药理学筛选评估显示8l对丝氨酸水解酶、激酶和药物靶点具有选择性。

  DOI：

  10.1021/acs.jmedchem.2c00162

文献信息

• Discovery and structure-activity relationship studies of 1-aryl-1H-naphtho[2,3-d][1,2,3]triazole-4,9-dione derivatives as potent dual inhibitors of indoleamine 2,3-dioxygenase 1 (IDO1) and trytophan 2,3-dioxygenase (TDO)
  作者：Shulei Pan、Yangli Zhou、Qiusheng Wang、Yanlin Wang、Chenyu Tian、Tianqi Wang、Luyi Huang、Jinshan Nan、Linli Li、Shengyong Yang

  DOI：10.1016/j.ejmech.2020.112703

  日期：2020.12

  Indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase (TDO), which mediate kynurenine pathway of tryptophan degradation, have emerged as potential new targets in immunotherapy for treatment of cancer because of their critical role in immunosuppression in the tumor microenvironment. In this investigation, we report the structural optimization and structure-activity relationship studies of 1-phenyl-1H-naphtho[2,3-d][1,2,3]triazole-4,9-dione derivatives as a new class of IDO1/TDO dual inhibitors. Among all the obtained dual inhibitors, 1-(3-chloro-4-fluorophenyl)-6-fluoro-1H-naphtho[2,3-d][1,2,3]triazole-4,9-dione (38) displayed the most potent IDO1 and TDO inhibitory activities with IC₅₀ (half-maximal inhibitory concentration) values of 5 nM for IDO1 and 4 nM for TDO. It turned out that compound 38 was not a PAINS compound. Compound 38 could efficiently inhibit the biofunction of IDO1 and TDO in intact cells. In LL2 (Lewis lung cancer) and Hepa1-6 (hepatic carcinoma) allograft mouse models, this compound also showed considerable in vivo anti-tumor activity and no obvious toxicity was observed. Therefore, 38 could be a good lead compound for cancer immunotherapy and deserving further investigation.