拉帕替尼杂质16 | 845271-73-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 中文名称: 拉帕替尼杂质16
• 英文名称: N-(3-chloro-4-((3-fluorobenzyl)oxy)phenyl)quinazolin-4-amine
• 英文别名: NEU-1010；N-[3-chloro-4-[(3-fluorophenyl)methoxy]phenyl]quinazolin-4-amine
• CAS: 845271-73-0
• 化学式: C₂₁H₁₅ClFN₃O
• 分子量: 379.821
• InChiKey: WSCIAEIHLKCXIK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  47
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  4-[3-氯-4-(3-氟苄基氧)苯基氨基]-6-碘喹唑啉 在 palladium diacetate 、 potassium carbonate 、 三苯基膦 作用下， 以 正丁醇 为溶剂， 反应 0.75h， 以26%的产率得到拉帕替尼杂质16
  参考文献：
  名称：

  Evaluation of aromatic 6-substituted thienopyrimidines as scaffolds against parasites that cause trypanosomiasis, leishmaniasis, and malaria

  摘要：

  人类酪氨酸激酶抑制剂骨架的再利用为生成抗寄生虫药物提供了新的引物化合物，为热带病提供了新的引物化合物。

  DOI：

  10.1039/c4md00441h

文献信息

• [EN] QUINAZOLINE COMPOUNDS<br/>[FR] COMPOSÉS À BASE DE QUINAZOLINE
  申请人：HUTCHISON MEDIPHARMA LTD

  公开号：WO2012000356A1

  公开（公告）日：2012-01-05

  Provided are certain quinazoline compounds, compositions thereof and methods of use thereof. These quinazoline compounds can effectively inhibit the overexpression and/or overactivity of epidermal growth factor receptor (EGFR).

  提供了某些喹噁啉化合物，它们的组成和使用方法。这些喹噁啉化合物可以有效地抑制表皮生长因子受体（EGFR）的过度表达和/或过度活性。
• Quinazoline Derivatives Having Tyrosine Kinase Inhibitory Activity
  申请人：Kume Masaharu

  公开号：US20090143414A1

  公开（公告）日：2009-06-04

  A compound which inhibits both of EGF receptor tyrosine kinase and HER2 tyrosine kinase is provided. A compound represented by the general formula (I): wherein R X is a group represented by the formula: wherein R 1 is a hydrogen atom, optionally substituted alkyl, etc.; Z is —O—, —N(R 10 )—, etc.; R 10 is a hydrogen atom, alkyl, etc.; R 2 is a hydrogen atom, optionally substituted alkyl, etc.; R 18 is a hydrogen atom, optionally substituted alkyl, etc.; R 19 is optionally substituted alkyl, etc.; W 1 is an optionally substituted non-aromatic nitrogen-containing group; R 17 is a hydrogen atom, optionally substituted alkyl, etc.; R 3 and R 4 are independently a hydrogen atom, optionally substituted alkyl, etc.; X is —O—, —S—, or —N(R 12 )—, etc.; R 12 is a hydrogen atom, alkyl, etc.; and A is phenyl optionally having a substituent, etc., its pharmaceutically acceptable salt, or a solvate thereof.

  提供了一种抑制EGF受体酪氨酸激酶和HER2酪氨酸激酶的化合物。该化合物由通式（I）表示：其中RX是由以下式子表示的基团：其中R1是氢原子，可选取代烷基等；Z是—O—，—N（R10）—等；R10是氢原子，烷基等；R2是氢原子，可选取代烷基等；R18是氢原子，可选取代烷基等；R19是可选取代烷基等；W1是可选取代非芳香族含氮基团；R17是氢原子，可选取代烷基等；R3和R4分别是氢原子，可选取代烷基等；X是—O—，—S—或—N（R12）—等；R12是氢原子，烷基等；A是苯基，可选取代基等，其药物可接受的盐或其溶剂化合物。
• QUINAZOLINE DERIVATIVES HAVING TYROSINE KINASE INHIBITORY ACTIVITY
  申请人：KUME Masaharu

  公开号：US20120123114A1

  公开（公告）日：2012-05-17

  A compound which inhibits both of EGF receptor tyrosine kinase and HER2 tyrosine kinase is provided. A compound represented by the general formula (I): wherein R X is a group represented by the formula: wherein R 1 is a hydrogen atom, optionally substituted alkyl, etc.; Z is —O—, —N(R 10 )—, etc.; R 10 is a hydrogen atom, alkyl, etc.; R 2 is a hydrogen atom, optionally substituted alkyl, etc.; R 18 is a hydrogen atom, optionally substituted alkyl, etc.; R 19 is optionally substituted alkyl, etc.; W 1 is an optionally substituted non-aromatic nitrogen-containing group; R 17 is a hydrogen atom, optionally substituted alkyl, etc.; R 3 and R 4 are independently a hydrogen atom, optionally substituted alkyl, etc.; X is —O—, —S—, or —N(R 12 )—, etc.; R 12 is a hydrogen atom, alkyl, etc.; and A is phenyl optionally having a substituent, etc., its pharmaceutically acceptable salt, or a solvate thereof.

  提供了一种同时抑制EGF受体酪氨酸激酶和HER2酪氨酸激酶的化合物。该化合物的普遍式表示为（I）：其中，RX是由以下式表示的基团：其中，R1是氢原子，可选地取代的烷基等；Z为—O—，—N(R10)—等；R10为氢原子，烷基等；R2为氢原子，可选地取代的烷基等；R18为氢原子，可选地取代的烷基等；R19为可选地取代的烷基等；W1为可选地取代的非芳香族含氮基团；R17为氢原子，可选地取代的烷基等；R3和R4分别为氢原子，可选地取代的烷基等；X为—O—，—S—或—N(R12)—等；R12为氢原子，烷基等；A为苯基，可选地具有取代基等，其药学上可接受的盐或其溶剂化物。
• Synthesis of Lapatinib via direct regioselective arylation of furfural
  作者：Greg Erickson、Jiasheng Guo、Mike McClure、Mark Mitchell、Marie-Catherine Salaun、Andrew Whitehead

  DOI：10.1016/j.tetlet.2014.09.039

  日期：2014.10

  A new synthesis of Lapatinib, an orally active drug for breast cancer, is described. The synthesis involves a palladium catalyzed regioselective arylation of furfural with 6-bromo-N-(3-chloro-4-((3-fluorobenzyl)oxy)phenyl)quinazolin-4-amine. This key step replaces an atom inefficient Suzuki cross coupling reaction used in a previously disclosed route and significantly shortens the synthesis. (C) 2014 Elsevier Ltd. All rights reserved.
• QUINAZOLINE DERIVATIVE HAVING TYROSINE KINASE INHIBITORY ACTIVITY
  申请人：SHIONOGI & CO., LTD.

  公开号：EP1854789B1

  公开（公告）日：2013-10-09