2-Chloro-5-nitro-4-(3-(trifluoromethyl)phenoxy)pyrimidine

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-Chloro-5-nitro-4-(3-(trifluoromethyl)phenoxy)pyrimidine
• 英文别名: 2-Chloro-5-nitro-4-[3-(trifluoromethyl)phenoxy]pyrimidine；2-chloro-5-nitro-4-[3-(trifluoromethyl)phenoxy]pyrimidine
• 化学式: C₁₁H₅ClF₃N₃O₃
• 分子量: 319.627
• InChiKey: PQWDMJKCTZLECM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  80.8
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  2-Chloro-5-nitro-4-(3-(trifluoromethyl)phenoxy)pyrimidine 在 palladium 10% on activated carbon 、 氢气 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 6.0h， 生成 4-fluoro-N-(4-(3-(trifluoromethyl)phenoxy)pyrimidin-5-yl)benzamide
  参考文献：
  名称：

  EGFR inhibitors from cancer to inflammation: Discovery of 4-fluoro-N-(4-(3-(trifluoromethyl)phenoxy)pyrimidin-5-yl)benzamide as a novel anti-inflammatory EGFR inhibitor

  摘要：

  EGFR inhibitors are well-known as anticancer agents. Quite differently, we report our effort to develop EGFR inhibitors as anti-inflammatory agents. Pyrimidinamide EGFR inhibitors eliciting low micromolar IC50 and the structurally close non-EGFR inhibitor urea analog were synthesized. Comparing their nitric oxide (NO) production inhibitory activity in peritoneal macrophages and RAW 246.7 macrophages indicated that their anti-inflammatory activity in peritoneal macrophages might be a sequence of EGFR inhibition. Further evaluations proved that compound 4d significantly and dose-dependently inhibits LPS-induced iNOS expression and IL-1 beta, IL-6, and TNF-alpha production via NF-kappa B inactivation in peritoneal macrophages. Compound 4d might serve as a lead compound for development of a novel class of anti-inflammatory EGFR inhibitors.

  DOI：

  10.1016/j.bioorg.2019.01.017
• 作为产物：
  描述：

  间三氟甲基苯酚 、 2,4-二氯-5 硝基嘧啶 在 碳酸氢钠 作用下， 以 水 、 丙酮 为溶剂， 反应 3.0h， 生成 2-Chloro-5-nitro-4-(3-(trifluoromethyl)phenoxy)pyrimidine
  参考文献：
  名称：

  EGFR inhibitors from cancer to inflammation: Discovery of 4-fluoro-N-(4-(3-(trifluoromethyl)phenoxy)pyrimidin-5-yl)benzamide as a novel anti-inflammatory EGFR inhibitor

  摘要：

  EGFR inhibitors are well-known as anticancer agents. Quite differently, we report our effort to develop EGFR inhibitors as anti-inflammatory agents. Pyrimidinamide EGFR inhibitors eliciting low micromolar IC50 and the structurally close non-EGFR inhibitor urea analog were synthesized. Comparing their nitric oxide (NO) production inhibitory activity in peritoneal macrophages and RAW 246.7 macrophages indicated that their anti-inflammatory activity in peritoneal macrophages might be a sequence of EGFR inhibition. Further evaluations proved that compound 4d significantly and dose-dependently inhibits LPS-induced iNOS expression and IL-1 beta, IL-6, and TNF-alpha production via NF-kappa B inactivation in peritoneal macrophages. Compound 4d might serve as a lead compound for development of a novel class of anti-inflammatory EGFR inhibitors.

  DOI：

  10.1016/j.bioorg.2019.01.017

文献信息

• EGFR inhibitors from cancer to inflammation: Discovery of 4-fluoro-N-(4-(3-(trifluoromethyl)phenoxy)pyrimidin-5-yl)benzamide as a novel anti-inflammatory EGFR inhibitor
  作者：Ahmed Elkamhawy、Ahmed H.E. Hassan、Sora Paik、Yong Sup Lee、Hwi-Ho Lee、Ji-Sun Shin、Kyung-Tae Lee、Eun Joo Roh

  DOI：10.1016/j.bioorg.2019.01.017

  日期：2019.5

  EGFR inhibitors are well-known as anticancer agents. Quite differently, we report our effort to develop EGFR inhibitors as anti-inflammatory agents. Pyrimidinamide EGFR inhibitors eliciting low micromolar IC50 and the structurally close non-EGFR inhibitor urea analog were synthesized. Comparing their nitric oxide (NO) production inhibitory activity in peritoneal macrophages and RAW 246.7 macrophages indicated that their anti-inflammatory activity in peritoneal macrophages might be a sequence of EGFR inhibition. Further evaluations proved that compound 4d significantly and dose-dependently inhibits LPS-induced iNOS expression and IL-1 beta, IL-6, and TNF-alpha production via NF-kappa B inactivation in peritoneal macrophages. Compound 4d might serve as a lead compound for development of a novel class of anti-inflammatory EGFR inhibitors.