N-(3-tert-butylisoxazol-5-yl)-2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)acetamide | 1267855-71-9

• 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: N-(3-tert-butylisoxazol-5-yl)-2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)acetamide
• 英文别名: N-(3-tert-butyl-1,2-oxazol-5-yl)-2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]acetamide
• CAS: 1267855-71-9
• 化学式: C₂₁H₂₉BN₂O₄
• 分子量: 384.283
• InChiKey: LOVDKXHCTCGLBT-UHFFFAOYSA-N

物化性质

• 沸点：
  559.5±50.0 °C(Predicted)
• 密度：
  1.12±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.45
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  73.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-氨基-5-溴吡啶 、 N-(3-tert-butylisoxazol-5-yl)-2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)acetamide 在 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 sodium carbonate 作用下， 以 水 、 乙腈 为溶剂， 反应 1.0h， 生成 2-(4-(6-aminopyridin-3-yl)phenyl)-N-(3-tert-butylisoxazol-5-yl)acetamide
  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：

  三甲基乙酸乙酯 在 sodium hydride 、 硫酸羟胺 、 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 、 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 31.0h， 生成 N-(3-tert-butylisoxazol-5-yl)-2-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)acetamide
  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

• BIARYL COMPOUNDS AND METHODS OF USE THEREOF
  申请人：Abraham Sunny

  公开号：US20130035326A1

  公开（公告）日：2013-02-07

  Provided herein are compounds for treatment of KIT, CSF-1R and/or FLT3 kinase mediated diseases. Also provided are pharmaceutical compositions comprising the compounds and methods of using the compounds and compositions.

  本文提供了用于治疗KIT、CSF-1R和/或FLT3激酶介导的疾病的化合物。还提供了包含这些化合物的制药组合物以及使用这些化合物和组合物的方法。
• 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.