4-(5-((4-bromo-3,5-dimethyl-1H-pyrazol-1-yl)methyl)furan-2-carboxamido)-1-ethyl-1H-pyrazole-3-carboxamide

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 4-(5-((4-bromo-3,5-dimethyl-1H-pyrazol-1-yl)methyl)furan-2-carboxamido)-1-ethyl-1H-pyrazole-3-carboxamide
• 英文别名: 4-[({5-[(4-bromo-3,5-dimethyl-1H-pyrazol-1-yl)methyl]furan-2-yl}carbonyl)amino]-1-ethyl-1H-pyrazole-3-carboxamide；4-[[5-[(4-bromo-3,5-dimethylpyrazol-1-yl)methyl]furan-2-carbonyl]amino]-1-ethylpyrazole-3-carboxamide
• 化学式: C₁₇H₁₉BrN₆O₃
• mdl: MFCD04044714
• 分子量: 435.28
• InChiKey: ZIIPBQJCNHJSMA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  121
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  3,5-二甲基-4-溴吡唑 在 potassium tert-butylate 、 四丁基碘化铵 、 氯化铵 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 、 sodium hydroxide 作用下， 以 四氢呋喃 、 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 57.16h， 生成 4-(5-((4-bromo-3,5-dimethyl-1H-pyrazol-1-yl)methyl)furan-2-carboxamido)-1-ethyl-1H-pyrazole-3-carboxamide
  参考文献：
  名称：

  Design, synthesis, and structure–activity relationships of 1-ethylpyrazole-3-carboxamide compounds as novel hypoxia-inducible factor (HIF)-1 inhibitors

  摘要：

  Hypoxia-inducible factor (HIF)-1 is well known as a promising target for cancer chemotherapy. By screening an in-house chemical library using a hypoxia-responsive luciferase reporter gene assay, we identified CLB-016 (1) containing 1-ethylpyrazole-3-carboxamide as a HIF-1 inhibitor (IC50 = 19.1 mu M). In a subsequent extensive structure-activity relationship (SAR) study, we developed compound 11Ae with an IC50 value of 8.1 mu M against HIF-1-driven luciferase activity. Compounds 1 and 11Ae were shown to significantly suppress the HIF-1-mediated hypoxia response, including carbonic anhydrase IX (CAIX) gene expression and migration of human sarcoma HT1080 cells. These results revealed 1-ethylpyrazole-3-carboxamide as a novel scaffold to develop promising anti-cancer drugs targeting the HIF-1 signaling pathway. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.02.038