N-(3-fluorophenyl)-2-{2-[(7-{3-[(2-hydroxyethyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1,3-thiazol-5-yl}acetamide | 723279-41-2

• 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: N-(3-fluorophenyl)-2-{2-[(7-{3-[(2-hydroxyethyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1,3-thiazol-5-yl}acetamide
• 英文别名: N-(3-fluorophenyl)-2-(2-(7-(3-(2-hydroxyethylamino)propoxy)-6-methoxyquinazolin-4-ylamino)thiazol-5-yl)acetamide；N-(3-fluorophenyl)-2-[2-[[7-[3-(2-hydroxyethylamino)propoxy]-6-methoxyquinazolin-4-yl]amino]-1,3-thiazol-5-yl]acetamide
• CAS: 723279-41-2
• 化学式: C₂₅H₂₇FN₆O₄S
• 分子量: 526.592
• InChiKey: UZWFLOSUVZITCB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  37
• 可旋转键数：
  13
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  159
• 氢给体数：
  4
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  N-(3-fluorophenyl)-2-{2-[(7-{3-[(2-hydroxyethyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1,3-thiazol-5-yl}acetamide 、 二碳酸二叔丁酯 以 DMF (N,N-dimethyl-formamide) 为溶剂， 反应 48.0h， 以43%的产率得到tert-butyl (3-((4-((5-(2-((3-fluorophenyl)amino)-2-oxoethyl)-1,3-thiazol-2-yl)amino)-6-methoxyquinazolin-7-yl)oxy)propyl)-(2-hydroxyethyl) carbamate
  参考文献：
  名称：

  [EN] QUINAZOLINE COMPOUNDS
  [FR] COMPOSES DE QUINAZOLINE

  摘要：

  式(I)中的喹唑啉衍生物，其中A是含有硫原子并且可选地含有一个或多个氮原子的5-成员杂芳基；含有它们的组合物，其制备方法以及它们在治疗中的用途。

  公开号：

  WO2004058752A1
• 作为产物：
  描述：

  [2-(tritylamino)-1,3-thiazol-5-yl]acetic acid 在 溶剂黄146 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 、 三氟乙酸 、 potassium iodide 作用下， 以 N-甲基吡咯烷酮 、 N,N-二甲基乙酰胺 、 N,N-二甲基甲酰胺 为溶剂， 反应 22.0h， 生成 N-(3-fluorophenyl)-2-{2-[(7-{3-[(2-hydroxyethyl)amino]propoxy}-6-methoxyquinazolin-4-yl)amino]-1,3-thiazol-5-yl}acetamide
  参考文献：
  名称：

  Discovery of Novel and Potent Thiazoloquinazolines as Selective Aurora A and B Kinase Inhibitors

  摘要：

  The synthesis of a novel series of quinazolines substituted at C4 by five-membered ring aminoheterocycles is reported. Their in vitro structure-activity relationships versus Aurora A and B serine-threonine kinases is discussed. Our results demonstrate that quinazolines with a substituted aminothiazole at C4 possess potent Aurora A and B inhibitory activity and excellent selectivity against a panel of various serine-threonine and tyrosine kinases, as exemplified by compound 46. We found also that the position and nature of the substituent on the thiazole play key roles in cellular potency. Compounds with an acetanilide substituent at C5' have the greatest cellular activity. The importance of the C5' position for substitution has been rationalized by ab initio molecular orbital calculations. Results show that the planar conformation with the sulfur of the thiazole next to the quinazoline N-3 is strongly favored over the other possible planar conformation. Compound 46 is a potent suppressor of the expression of phospho-histone H3 in tumor cells in vitro as well as in vivo, where 46, administered as its phosphate prodrug 54, suppresses the expression of phospho-histone H3 in subcutaneously implanted tumors in nude mice.

  DOI：

  10.1021/jm050786h