6-(4-Aminophenyl)pyridazin-3-amine | 1215073-63-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 6-(4-Aminophenyl)pyridazin-3-amine
• CAS: 1215073-63-4
• 化学式: C₁₀H₁₀N₄
• 分子量: 186.216
• InChiKey: GXBRVSRRQOBFIN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  77.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-叔丁基异噁唑-3-基氨基甲酸苯酯 、 6-(4-Aminophenyl)pyridazin-3-amine 在 4-二甲氨基吡啶 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 生成
  参考文献：
  名称：

  Discovery and optimization of a highly efficacious class of 5-aryl-2-aminopyridines as FMS-like tyrosine kinase 3 (FLT3) inhibitors

  摘要：

  Based on a putative binding mode of quizartinib (AC220, 1), a potent FMS-like tyrosine kinase 3 (FLT3) inhibitor in Phase III clinical development, we have designed de novo a simpler aminopyridine-based hinge binding motif. Further optimization focusing on maximizing in vivo efficacy and minimizing CYP3A4 time-dependent inhibition resulted in a highly efficacious compound (6s) in tumor xenograft model for further preclinical development. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.07.023
• 作为产物：
  描述：

  4-(N-Boc-氨基)苯硼酸 在 四(三苯基膦)钯 、 potassium carbonate 、 三氟乙酸 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 水 为溶剂， 反应 4.33h， 生成 6-(4-Aminophenyl)pyridazin-3-amine
  参考文献：
  名称：

  Discovery and optimization of a highly efficacious class of 5-aryl-2-aminopyridines as FMS-like tyrosine kinase 3 (FLT3) inhibitors

  摘要：

  Based on a putative binding mode of quizartinib (AC220, 1), a potent FMS-like tyrosine kinase 3 (FLT3) inhibitor in Phase III clinical development, we have designed de novo a simpler aminopyridine-based hinge binding motif. Further optimization focusing on maximizing in vivo efficacy and minimizing CYP3A4 time-dependent inhibition resulted in a highly efficacious compound (6s) in tumor xenograft model for further preclinical development. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.07.023

文献信息

• Microwave-enhanced synthesis of 2,3,6-trisubstituted pyridazines: application to four-step synthesis of gabazine (SR-95531)
  作者：Navnath Gavande、Graham A. R. Johnston、Jane R. Hanrahan、Mary Chebib

  DOI：10.1039/c0ob00004c

  日期：——

  Microwave-enhanced, highly efficient protocols for the synthesis of synthetically and biologically important 2,3,6-trisubstituted pyridazine architectures have been developed by sequential amination/Suzuki coupling/alkylation reactions. This powerful strategy is an economical and highly chemoselective protocol for the synthesis of diversified pyridazines. The total synthesis of gabazine (SR-95531)

  微波增强的，高效的合成和生物学上重要的2,3,6-三取代合成方案 哒嗪通过顺序胺化/ Suzuki偶联/烷基化反应已经开发出各种结构。这种强大的策略是用于合成多种哒嗪的经济且高度化学选择性的方案。川ab嗪的全合成（SR-95531）可通过四个步骤采用多功能策略实现，总收率达到73％。
• Discovery and optimization of a highly efficacious class of 5-aryl-2-aminopyridines as FMS-like tyrosine kinase 3 (FLT3) inhibitors
  作者：Gang Liu、Sunny Abraham、Xing Liu、Shimin Xu、Allison M. Rooks、Ron Nepomuceno、Alan Dao、Daniel Brigham、Dana Gitnick、Darren E. Insko、Michael F. Gardner、Patrick P. Zarrinkar、Ron Christopher、Barbara Belli、Robert C. Armstrong、Mark W. Holladay

  DOI：10.1016/j.bmcl.2015.07.023

  日期：2015.9

  Based on a putative binding mode of quizartinib (AC220, 1), a potent FMS-like tyrosine kinase 3 (FLT3) inhibitor in Phase III clinical development, we have designed de novo a simpler aminopyridine-based hinge binding motif. Further optimization focusing on maximizing in vivo efficacy and minimizing CYP3A4 time-dependent inhibition resulted in a highly efficacious compound (6s) in tumor xenograft model for further preclinical development. (C) 2015 Elsevier Ltd. All rights reserved.