4-((4-chloro-2-fluorophenyl)amino)-6,7-dimethoxyquinoline-3-carboxamide | 476191-84-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 4-((4-chloro-2-fluorophenyl)amino)-6,7-dimethoxyquinoline-3-carboxamide
• 英文别名: 4-(4-Chloro-2-fluorophenylamino)-6,7-dimethoxyquinoline-3-carboxamide；4-(4-chloro-2-fluoroanilino)-6,7-dimethoxyquinoline-3-carboxamide
• CAS: 476191-84-1
• 化学式: C₁₈H₁₅ClFN₃O₃
• 分子量: 375.787
• InChiKey: SSSQBBWJMZYDLU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  86.5
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  4-氯-6,7-二甲氧基喹啉-3-羧酸乙酯 在 水 、 氯化铵 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 、 sodium hydroxide 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 、 异丙醇 为溶剂， 反应 42.0h， 生成 4-((4-chloro-2-fluorophenyl)amino)-6,7-dimethoxyquinoline-3-carboxamide
  参考文献：
  名称：

  Potent and Selective Inhibitors of MTH1 Probe Its Role in Cancer Cell Survival

  摘要：

  Recent literature has claimed that inhibition of the enzyme MTH1 can eradicate cancer. MTH1 is one of the "housekeeping" enzymes that are responsible for hydrolyzing damaged nucleotides in cells and thus prevent them from being incorporated into DNA. We have developed orthogonal and chemically distinct tool compounds to those published in the literature to allow us to test the hypothesis that inhibition of MTH1 has wide applicability in the treatment of cancer. Here we present the work that led to the discovery of three structurally different series of MTH1 inhibitors with excellent potency, selectivity, and proven target engagement in cells. None of these compounds elicited the reported cellular phenotype, and additional siRNA and CRISPR experiments further support these observations. Critically, the difference between the responses of our highly selective inhibitors and published tool compounds suggests that the effect reported for the latter may be due to off-target cytotoxic effects. As a result, we conclude that the role of MTH1 in carcinogenesis and utility of its inhibition is yet to be established.

  DOI：

  10.1021/acs.jmedchem.5b01760

文献信息

• Novel 4-anilinoquinoline-3-carboxamides
  申请人：——

  公开号：US20040248923A1

  公开（公告）日：2004-12-09

  The present invention relates to novel compounds of formula (IA), which are JAK3 Kinase inhibitors, methods for their preparation and pharmaceutical compositions comprising them.

  本发明涉及公式（IA）的新型化合物，它们是JAK3激酶抑制剂，以及它们的制备方法和包含它们的药物组合物。
• Identification of 3-amido-4-anilinoquinolines as potent and selective inhibitors of CSF-1R kinase
  作者：David A. Scott、Carrie L. Balliet、Donald J. Cook、Audrey M. Davies、Thomas W. Gero、Charles A. Omer、Srinivasu Poondru、Maria-Elena Theoclitou、Boris Tyurin、Michael J. Zinda

  DOI：10.1016/j.bmcl.2008.12.046

  日期：2009.2

  3-Amido-4-anilinoquinolines are potent and highly selective inhibitors of CSF-1R. Their synthesis and SAR is reported, along with initial efforts to optimize the physical properties and PK through modi. cations at the quinoline 6- and 7-positions. (c) 2008 Elsevier Ltd. All rights reserved.
• NOVEL 4-ANILINOQUINOLINE-3-CARBOXAMIDES
  申请人：AstraZeneca AB

  公开号：EP1387830A1

  公开（公告）日：2004-02-11
• US7037925B2
  申请人：——

  公开号：US7037925B2

  公开（公告）日：2006-05-02
• [EN] NOVEL 4-ANILINOQUINOLINE-3-CARBOXAMIDES<br/>[FR] NOUVEAUX 4-ANILINOQUINOLINE-3-CARBOXAMIDES
  申请人：ASTRAZENECA AB

  公开号：WO2002092571A1

  公开（公告）日：2002-11-21

  The present invention relates to novel compounds of formula (IA), which are JAK3 Kinase inhibitors, methods for their preparation and pharmaceutical compositions comprising them.