伊马替尼杂质E | 571186-91-9

• 物质功能分类: 原料药 - 抗肿瘤药 - 替尼类抗肿瘤药
• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 伊马替尼杂质E
• 中文别名: 伊马替尼进口标准杂质D；4-氧代伊马替尼；伊马替尼（哌啶）-N-氧化物；伊马替尼(哌啶)-N-氧化物
• 英文名称: 4-[(4-methyl-4-oxido-1-piperazinyl)methyl]-N-[4-methyl-3-[[4-(3-pyridinyl)-2-pyrimidinyl]amino]-phenyl]benzamide
• 英文别名: 4-(4-methyl-4-oxypiperazin-1-ylmethyl)-N-[4-methyl-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)phenyl]benzamide；imatinib (piperidine)-N-oxide；1-methyl-4-(4-((4-methyl-3-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)phenyl)carbamoyl)benzyl)piperazine-1-oxide；imatinib (piperidine)-4-oxide；CGP 71422；4-[(4-methyl-4-oxidopiperazin-4-ium-1-yl)methyl]-N-[4-methyl-3-[(4-pyridin-3-ylpyrimidin-2-yl)amino]phenyl]benzamide
• CAS: 571186-91-9
• 化学式: C₂₉H₃₁N₇O₂
• 分子量: 509.611
• InChiKey: MSADRWGPCQTOST-UHFFFAOYSA-N

物化性质

• 熔点：
  146-149°C
• 溶解度：
  氯仿（微溶）、甲醇（微溶、加热）

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  38
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  101
• 氢给体数：
  2
• 氢受体数：
  7

安全信息

• 海关编码：
  29333990
• 储存条件：
  hygroscopic, stored at -20°C in a freezer under an inert atmosphere

反应信息

• 作为产物：
  描述：

  伊马替尼 在 间氯过氧苯甲酸 作用下， 生成 伊马替尼杂质E
  参考文献：
  名称：

  Investigations into the Potential Role of Metabolites on the Anti-Leukemic Activity of Imatinib, Nilotinib and Midostaurin

  摘要：

  药物的功效和副作用不仅仅反映了母化合物的生化和药效特性，而且通常包括母化合物和活性代谢物之间的协同效应。已经合成和评估了伊马替尼、尼洛替尼和米多斯他林的代谢物，以比较它们作为蛋白激酶抑制剂的特性与母药的区别。伊马替尼的N-去甲基代谢物作为BCR-ABL1激酶抑制剂的活性明显低于伊马替尼，这解释了为什么产生高水平该代谢物的患者在慢性髓细胞白血病（CML）治疗中显示相对较低的反应率。伊马替尼和尼洛替尼的羟甲基苯和N-氧代谢物作为BCR-ABL1抑制剂的活性很弱，不太可能在CML中发挥作用。米多斯他林的3-(R)-HO-代谢物在长期用药后显示出明显的积累，并且除了FLT3的突变形式外，还强力抑制PDPK1和VEGFR2激酶（IC50值

  DOI：

  10.2533/chimia.2019.561

文献信息

• METHODS AND INTERMEDIATES FOR THE PREPARATION OF OPTIONALLY RADIO-LABELED IMATINIB
  申请人：Salter Rhys

  公开号：US20090299064A1

  公开（公告）日：2009-12-03

  The invention relates to new processes for the manufacture of N-5-[4-(4-methyl-piperazino-methyl)-benzoylamido]-2-methylphenyl}4-(3-pyridyl)-2-pyrimidine-amine (compound of formula I, new processes for the manufacture of metabolites of N-5-[4-(4-methyl-piperazino-methyl)-benzoylamido]-2-methylphenyl}-4-(3-pyridyl)-2-pyrimidine-amine observed after administration of the compound to warm-blooded animals as well as to intermediates used in said processes. New starting materials as well as processes for the preparation thereof are likewise the subject of this invention. The processes described herein are especially suitable to furnish said compounds having isotopic labeling. The such obtained labeled compounds are in particular suitable to track and to investigate into the metabolism of N-5-[4-(4-methyl-piperazino-methyl)-benzoylamido]-2-methylphenyl}4-(3-pyridyl)-2-pyrimidine-amine and its pharmaceutically acceptable salts in clinical and pre-clinical studies.

  本发明涉及制备N-5-[4-(4-甲基哌嗪甲基)-苯甲酰氨基]-2-甲基苯基}4-(3-吡啶基)-2-嘧啶胺（式I化合物）的新工艺，制备该化合物在恒温动物体内代谢产物的新工艺，以及用于该工艺的中间体。本发明还涉及新的起始材料及其制备工艺。本文所述的工艺特别适用于获得具有同位素标记的化合物。这些获得的标记化合物特别适用于跟踪和研究N-5-[4-(4-甲基哌嗪甲基)-苯甲酰氨基]-2-甲基苯基}4-(3-吡啶基)-2-嘧啶胺及其药学上可接受的盐在临床和临床前研究中的代谢。
• Methods and Intermediates for the Preparation of Optionally Radio-Labeled Imatinib
  申请人：Salter Rhys

  公开号：US20120316338A1

  公开（公告）日：2012-12-13

  The invention relates to new processes for the manufacture of N-5-[4-(4-methyl-piperazino-methyl)-benzoylamido]-2-methylphenyl}-4-(3-pyridyl)-2-pyrimidine-amine (compound of formula I, new processes for the manufacture of metabolites of N-5[4-(4-methyl-piperazino-methyl)-benzoylamido]-2-methylphenyl}-4-(3-pyridyl)-2-pyrimidine-amine observed after administration of the compound to warm-blooded animals as well as to intermediates used in said processes. New starting materials as well as processes for the preparation thereof are likewise the subject of this invention. The processes described herein are especially suitable to furnish said compounds having isotopic labeling. The such obtained labeled compounds are in particular suitable to track and to investigate into the metabolism of N-5-[4-(4-methyl-piperazino-methyl)-benzoylamido]-2-methylphenyl}-4-(3-pyridyl)-2-pyrimidine-amine and its pharmaceutically acceptable salts in clinical and pre-clinical studies.

  本发明涉及制备N-5-[4-(4-甲基哌嗪甲基)-苯甲酰氨基]-2-甲基苯基}-4-(3-吡啶基)-2-嘧啶胺（化合物I的公式），制备该化合物在温血动物中给药后代谢产物的新工艺，以及用于该工艺的中间体。本发明还涉及新的起始材料及其制备工艺。本文所述的工艺特别适用于提供具有同位素标记的上述化合物。因此获得的标记化合物特别适用于跟踪并研究N-5-[4-(4-甲基哌嗪甲基)-苯甲酰氨基]-2-甲基苯基}-4-(3-吡啶基)-2-嘧啶胺及其药学上可接受的盐在临床和临床前研究中的代谢。
• N-oxyde of n-phenyl-2-pyrimidine-amine derivatives
  申请人：Bornsen Olaf Klaus

  公开号：US20050209452A1

  公开（公告）日：2005-09-22

  The invention relates to N-phenyl-2-pyrimidine-amine derivatives in which at least one nitrogen atom carries an oxygen atom to form the corresponding N-oxides, to processes for the preparation thereof, to pharmaceutical compositions comprising those compounds, and to the use thereof in the preparation of pharmaceutical compositions for the therapeutic treatment of warm-blooded animals, including humans.

  本发明涉及N-苯基-2-嘧啶胺衍生物，其中至少一个氮原子携带一个氧原子以形成相应的N-氧化物，以及制备这些化合物的过程，包括这些化合物的药物组成物和在制备温血动物，包括人类的治疗性药物组成物中的用途。
• N-OXIDES OF N-PHENYL-2-PYRIMIDINE-AMINE DERIVATIVES
  申请人：BORNSEN Klaus Olaf

  公开号：US20090239879A1

  公开（公告）日：2009-09-24

  The invention relates to N-phenyl-2-pyrimidine-amine derivatives derivatives in which at least one nitrogen atom carries an oxygen atom to form the corresponding N-oxides, to processes for the preparation thereof, to pharmaceutical compositions comprising those compounds, and to the use thereof in the preparation of pharmaceutical compositions for the therapeutic treatment of warm-blooded animals, including humans.

  该发明涉及N-苯基-2-嘧啶胺衍生物，其中至少有一个氮原子携带氧原子以形成相应的N-氧化物，以及其制备过程、包含这些化合物的制药组合物以及在制备治疗温血动物，包括人类的制药组合物时的使用。
• N-Oxides of n-Phenyl-2-pyrimidine-amine Derivatives
  申请人：Börnsen Klaus Olaf

  公开号：US20110294820A1

  公开（公告）日：2011-12-01

  The invention relates to N-phenyl-2-pyrimidine-amine derivatives derivatives in which at least one nitrogen atom carries an oxygen atom to form the corresponding N-oxides, to processes for the preparation thereof, to pharmaceutical compositions comprising those compounds, and to the use thereof in the preparation of pharmaceutical compositions for the therapeutic treatment of warm-blooded animals, including humans.

  该发明涉及N-苯基-2-嘧啶胺衍生物，其中至少一个氮原子携带氧原子以形成相应的N-氧化物，以及其制备方法、包含这些化合物的药物组合物和将其用于制备治疗温血动物，包括人类的药物组合物的用途。