N-(2-chloropyrimidin-4-yl)-N,2-dimethyl-2H-indazol-6-amine | 1042367-09-8

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: N-(2-chloropyrimidin-4-yl)-N,2-dimethyl-2H-indazol-6-amine
• 英文别名: N-(2-chloro-4-pyrimidinyl)-N,2-dimethyl-2H-indazol-6-amine；N-(2-Chloropyrimidin-4-yl)-N,2-dimethyl-2H-indazol-6-amine；N-(2-chloropyrimidin-4-yl)-N,2-dimethylindazol-6-amine
• CAS: 1042367-09-8
• 化学式: C₁₃H₁₂ClN₅
• 分子量: 273.725
• InChiKey: SNIQDOUJPYLPOX-UHFFFAOYSA-N

物化性质

• 沸点：
  514.3±25.0 °C(Predicted)
• 密度：
  1.37±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  46.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-(2-chloropyrimidin-4-yl)-N,2-dimethyl-2H-indazol-6-amine 、 对三氟甲氧基苯胺 在 盐酸 作用下， 以 乙醇 、 水 为溶剂， 反应 3.0h， 以71%的产率得到N⁴-methyl-N⁴-(2-methyl-2H-indazol-6-yl)-N²-(4-(trifluoromethoxy)phenyl)pyrimidine-2,4-diamine
  参考文献：
  名称：

  Synthesis and biological evaluation of novel pazopanib derivatives as antitumor agents

  摘要：

  A series of novel pazopanib derivatives, 7a-m, were designed and synthesized by modification of terminal benzene and indazole rings in pazopanib. The structures of all the synthesized compounds were confirmed by H-1 NMR and MS. Their inhibitory activity against VEGFR-2, PDGFR-alpha and c-kit tyrosine kinases were evaluated. All the compounds exhibited definite kinase inhibition, in which compound 7l was most potent with IC50 values of 12 nM against VEGFR-2. Furthermore, compounds 7c, 7d and 7m demonstrated comparable inhibitory activity against three tyrosine kinases to pazopanib, and compound 7f showed superior inhibitory effects than that of pazopanib. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.01.003
• 作为产物：
  描述：

  6-硝基吲唑 在 三乙烯二胺 、 palladium 10% on activated carbon 、 氢气 、 碳酸氢钠 、 caesium carbonate 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 29.25h， 生成 N-(2-chloropyrimidin-4-yl)-N,2-dimethyl-2H-indazol-6-amine
  参考文献：
  名称：

  Synthesis and biological evaluation of novel pazopanib derivatives as antitumor agents

  摘要：

  A series of novel pazopanib derivatives, 7a-m, were designed and synthesized by modification of terminal benzene and indazole rings in pazopanib. The structures of all the synthesized compounds were confirmed by H-1 NMR and MS. Their inhibitory activity against VEGFR-2, PDGFR-alpha and c-kit tyrosine kinases were evaluated. All the compounds exhibited definite kinase inhibition, in which compound 7l was most potent with IC50 values of 12 nM against VEGFR-2. Furthermore, compounds 7c, 7d and 7m demonstrated comparable inhibitory activity against three tyrosine kinases to pazopanib, and compound 7f showed superior inhibitory effects than that of pazopanib. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.01.003

文献信息

• Discovery of 5-[[4-[(2,3-Dimethyl-2<i>H</i>-indazol-6-yl)methylamino]-2-pyrimidinyl]amino]-2-methyl-benzenesulfonamide (Pazopanib), a Novel and Potent Vascular Endothelial Growth Factor Receptor Inhibitor
  作者：Philip A. Harris、Amogh Boloor、Mui Cheung、Rakesh Kumar、Renae M. Crosby、Ronda G. Davis-Ward、Andrea H. Epperly、Kevin W. Hinkle、Robert N. Hunter、Jennifer H. Johnson、Victoria B. Knick、Christopher P. Laudeman、Deirdre K. Luttrell、Robert A. Mook、Robert T. Nolte、Sharon K. Rudolph、Jerzy R. Szewczyk、Anne T. Truesdale、James M. Veal、Liping Wang、Jeffrey A. Stafford

  DOI：10.1021/jm800566m

  日期：2008.8.1

  Inhibition of the vascular endothelial growth factor (VEGF) signaling pathway has emerged as one of the most promising new approaches for cancer therapy. We describe herein the key steps starting from an initial screening hit leading to the discovery of pazopanib, N(4)-(2,3-dimethyl-2H-indazol-6-yl)-N(4)-methyl-N(2)-(4-methyl-3-sulfonamidophenyl)-2,4-pyrimidinediamine, a potent pan-VEGF receptor (VEGFR) inhibitor under clinical development for renal-cell cancer and other solid tumors.
• Synthesis and biological evaluation of novel pazopanib derivatives as antitumor agents
  作者：Haofei Qi、Ligong Chen、Bingni Liu、Xinran Wang、Li Long、Dengke Liu

  DOI：10.1016/j.bmcl.2014.01.003

  日期：2014.2

  A series of novel pazopanib derivatives, 7a-m, were designed and synthesized by modification of terminal benzene and indazole rings in pazopanib. The structures of all the synthesized compounds were confirmed by H-1 NMR and MS. Their inhibitory activity against VEGFR-2, PDGFR-alpha and c-kit tyrosine kinases were evaluated. All the compounds exhibited definite kinase inhibition, in which compound 7l was most potent with IC50 values of 12 nM against VEGFR-2. Furthermore, compounds 7c, 7d and 7m demonstrated comparable inhibitory activity against three tyrosine kinases to pazopanib, and compound 7f showed superior inhibitory effects than that of pazopanib. (C) 2014 Elsevier Ltd. All rights reserved.