di-tert-butyl {(2R)-1-[3-({4-[(1-{2-[(2,3-difluorophenyl)amino]-2-oxoethyl}-1H-pyrazol-4-yl)amino]quinazolin-7-yl}oxy)propyl]pyrrolidin-2-yl}methyl phosphate | 786685-37-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: di-tert-butyl {(2R)-1-[3-({4-[(1-{2-[(2,3-difluorophenyl)amino]-2-oxoethyl}-1H-pyrazol-4-yl)amino]quinazolin-7-yl}oxy)propyl]pyrrolidin-2-yl}methyl phosphate
• 英文别名: ditert-butyl [(2R)-1-[3-[4-[[1-[2-(2,3-difluoroanilino)-2-oxoethyl]pyrazol-4-yl]amino]quinazolin-7-yl]oxypropyl]pyrrolidin-2-yl]methyl phosphate
• CAS: 786685-37-8
• 化学式: C₃₅H₄₆F₂N₇O₆P
• 分子量: 729.764
• InChiKey: PLVKEOKUZNDXJY-RUZDIDTESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  51
• 可旋转键数：
  17
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.49
• 拓扑面积：
  142
• 氢给体数：
  2
• 氢受体数：
  13

反应信息

• 作为反应物：
  描述：

  di-tert-butyl {(2R)-1-[3-({4-[(1-{2-[(2,3-difluorophenyl)amino]-2-oxoethyl}-1H-pyrazol-4-yl)amino]quinazolin-7-yl}oxy)propyl]pyrrolidin-2-yl}methyl phosphate 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 生成 {(2R)-1-[3-({4-[(1-{2-[(2,3-difluorophenyl)amino]-2-oxoethyl}-1H-pyrazol-4-yl)amino]quinazolin-7-yl}oxy)propyl]pyrrolidin-2-yl}methyl dihydrogen phosphate
  参考文献：
  名称：

  Synthesis and SAR of 1-acetanilide-4-aminopyrazole-substituted quinazolines: Selective inhibitors of Aurora B kinase with potent anti-tumor activity

  摘要：

  A new class of 1-acetanilide-4-aminopyrazole-substituted quinazoline Aurora kinase inhibitors has been discovered possessing highly potent cellular activity. Continuous infusion into athymic mice bearing SW620 tumors of the soluble phosphate derivative 2 led to dose-proportional exposure of the des-phosphate compound 8 with a high-unbound fraction. The combination of potent cell activity and high free-drug exposure led to pharmacodynamic changes in the tumor at low doses, indicative of Aurora B-kinase inhibition and a reduction in tumor volume. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.02.002
• 作为产物：
  描述：

  在 双氧水 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 di-tert-butyl {(2R)-1-[3-({4-[(1-{2-[(2,3-difluorophenyl)amino]-2-oxoethyl}-1H-pyrazol-4-yl)amino]quinazolin-7-yl}oxy)propyl]pyrrolidin-2-yl}methyl phosphate
  参考文献：
  名称：

  Synthesis and SAR of 1-acetanilide-4-aminopyrazole-substituted quinazolines: Selective inhibitors of Aurora B kinase with potent anti-tumor activity

  摘要：

  A new class of 1-acetanilide-4-aminopyrazole-substituted quinazoline Aurora kinase inhibitors has been discovered possessing highly potent cellular activity. Continuous infusion into athymic mice bearing SW620 tumors of the soluble phosphate derivative 2 led to dose-proportional exposure of the des-phosphate compound 8 with a high-unbound fraction. The combination of potent cell activity and high free-drug exposure led to pharmacodynamic changes in the tumor at low doses, indicative of Aurora B-kinase inhibition and a reduction in tumor volume. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.02.002

文献信息

• Synthesis and SAR of 1-acetanilide-4-aminopyrazole-substituted quinazolines: Selective inhibitors of Aurora B kinase with potent anti-tumor activity
  作者：Kevin M. Foote、Andrew A. Mortlock、Nicola M. Heron、Frédéric H. Jung、George B. Hill、Georges Pasquet、Madeleine C. Brady、Stephen Green、Simon P. Heaton、Sarah Kearney、Nicholas J. Keen、Rajesh Odedra、Stephen R. Wedge、Robert W. Wilkinson

  DOI：10.1016/j.bmcl.2008.02.002

  日期：2008.3

  A new class of 1-acetanilide-4-aminopyrazole-substituted quinazoline Aurora kinase inhibitors has been discovered possessing highly potent cellular activity. Continuous infusion into athymic mice bearing SW620 tumors of the soluble phosphate derivative 2 led to dose-proportional exposure of the des-phosphate compound 8 with a high-unbound fraction. The combination of potent cell activity and high free-drug exposure led to pharmacodynamic changes in the tumor at low doses, indicative of Aurora B-kinase inhibition and a reduction in tumor volume. (C) 2008 Elsevier Ltd. All rights reserved.