di-tert-butyl {1-[3-({4-[(5-{2-[(3-fluorophenyl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)amino]-6-methoxyquinazolin-7-yl}oxy)propyl]piperidin-4-yl}methyl phosphate | 723278-14-6

• 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 {1-[3-({4-[(5-{2-[(3-fluorophenyl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)amino]-6-methoxyquinazolin-7-yl}oxy)propyl]piperidin-4-yl}methyl phosphate
• 英文别名: Di(tert-butyl) (1-(3-((4-((5-(2-((3-fluorophenyl)amino)-2-oxoethyl)-1,3-thiazol-2-yl)amino)-6-methoxyquinazolin-7-yl)oxy)propyl)piperidin-4-yl)methyl phosphate；ditert-butyl [1-[3-[4-[[5-[2-(3-fluoroanilino)-2-oxoethyl]-1,3-thiazol-2-yl]amino]-6-methoxyquinazolin-7-yl]oxypropyl]piperidin-4-yl]methyl phosphate
• CAS: 723278-14-6
• 化学式: C₃₇H₅₀FN₆O₇PS
• 分子量: 772.878
• InChiKey: PPEVZMSTZRHWSH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  53
• 可旋转键数：
  18
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.51
• 拓扑面积：
  175
• 氢给体数：
  2
• 氢受体数：
  14

反应信息

• 作为反应物：
  描述：

  di-tert-butyl {1-[3-({4-[(5-{2-[(3-fluorophenyl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)amino]-6-methoxyquinazolin-7-yl}oxy)propyl]piperidin-4-yl}methyl phosphate 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 反应 18.0h， 以98%的产率得到{1-[3-({4-[(5-{2-[(3-fluorophenyl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)amino]-6-methoxyquinazolin-7-yl}oxy)propyl]piperidin-4-yl}methyl dihydrogen phosphate
  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
• 作为产物：
  描述：

  [2-(tritylamino)-1,3-thiazol-5-yl]acetic acid 在 四氮唑 、 双氧水 、 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 26.0h， 生成 di-tert-butyl {1-[3-({4-[(5-{2-[(3-fluorophenyl)amino]-2-oxoethyl}-1,3-thiazol-2-yl)amino]-6-methoxyquinazolin-7-yl}oxy)propyl]piperidin-4-yl}methyl phosphate
  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

文献信息

• Quinazoline compounds
  申请人：Mortlock Austen Andrew

  公开号：US20060058523A1

  公开（公告）日：2006-03-16

  Quinazoline derivatives of formula (I) wherein A is 5-membered heteroaryl containing a sulphur atom and optionally containing one or more nitrogen atoms; compositions containing them, processes for their preparation and their use in therapy.

  公式（I）中的喹嗪啉衍生物，其中A是含有硫原子并可选地含有一个或多个氮原子的五元杂环芳基；包含它们的组合物，制备它们的过程以及它们在治疗中的使用。