6-methoxy-7-(3-morpholin-4-ylpropoxy)-4-(4-phenoxyphenylamino)quinoline-3-carbonitrile

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 6-methoxy-7-(3-morpholin-4-ylpropoxy)-4-(4-phenoxyphenylamino)quinoline-3-carbonitrile
• 英文别名: 6-Methoxy-7-(3-morpholin-4-yl-propoxy)-4-(4-phenoxy-phenylamino)-quinoline-3-carbonitrile；6-methoxy-7-(3-morpholin-4-ylpropoxy)-4-(4-phenoxyanilino)quinoline-3-carbonitrile
• 化学式: C₃₀H₃₀N₄O₄
• 分子量: 510.593
• InChiKey: LFTHSVHVSCMOQP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  38
• 可旋转键数：
  10
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  88.9
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  香草酸甲酯 在 (C₈H₁₇)3N(CH₃)Cl 、 硝酸 、 铁粉 、 potassium carbonate 、 氯化铵 、 溶剂黄146 、 sodium iodide 、 三氯氧磷 作用下， 以 四氢呋喃 、 甲醇 、 乙二醇乙醚 、 乙二醇二甲醚 、 丙酮 为溶剂， 生成 6-methoxy-7-(3-morpholin-4-ylpropoxy)-4-(4-phenoxyphenylamino)quinoline-3-carbonitrile
  参考文献：
  名称：

  Synthesis and Structure–Activity Relationships of 3-Cyano-4-(phenoxyanilino)quinolines as MEK (MAPKK) Inhibitors

  摘要：

  A series of 3-cyano-4-(phenoxyanilino)cyanoquinolines has been prepared as MEK (MAP kinase kinase) inhibitors. The best activity is seen with alkoxy groups at both the 6- and 7-positions. The lead compounds show low nanomolar IC50's against MAP kinase kinase, and have potent inhibitory activity in tumor cells. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(00)00580-1

文献信息

• Compositions and methods using hdm2 antagonist and mek inhibitor
  申请人：SANOFI

  公开号：EP2752191A1

  公开（公告）日：2014-07-09

  Methods of causing growth inhibition of cancer cells are provided, wherein the methods comprise contacting cancer cells with an HDM2 antagonist and a MEK inhibitor. Compositions in which the HDM2 antagonist and MEK inhibitor are combined also are provided.

  提供了抑制癌细胞生长的方法，其中包括用 HDM2 拮抗剂和 MEK 抑制剂接触癌细胞。还提供了将 HDM2 拮抗剂和 MEK 抑制剂结合在一起的组合物。
• MEDICAL USES INVOLVING C-RAF MUTANTS THAT CONFER RESISTANCE TO RAF INHIBITORS
  申请人：Dana Farber Cancer Institute, Inc.

  公开号：EP3693741A1

  公开（公告）日：2020-08-12

  Nucleic acids and proteins having a mutant C-RAF sequence, and methods of identifying patients having cancer who are likely to benefit from a combination therapy and methods of treatment are provided.

  本研究提供了具有突变 C-RAF 序列的核酸和蛋白质，以及识别可能从联合疗法中获益的癌症患者的方法和治疗方法。
• MEK1 mutation conferring resistance to RAF and MEK inhibitors
  申请人：Dana-Farber Cancer Institute, Inc.

  公开号：US10788496B2

  公开（公告）日：2020-09-29

  Nucleic acids and proteins having a mutant MEK sequence, and methods concerning identification of patients having resistance to treatment with anti-cancer agents, specifically inhibitors of RAF or MEK are provided. Methods of treatment and for optimizing treatment for patients having a mutation in a MEK1 sequence are also provided.

  本研究提供了具有突变 MEK 序列的核酸和蛋白质，以及有关鉴定对抗癌剂（特别是 RAF 或 MEK 抑制剂）治疗具有抗药性的患者的方法。还提供了针对 MEK1 序列突变患者的治疗方法和优化治疗的方法。
• Methods of identifying responses to map kinase inhibition therapy
  申请人：The Broad Institute, Inc.

  公开号：US10968484B2

  公开（公告）日：2021-04-06

  The invention provides methods and devices for determining molecular signatures in a cancer that predict response to a MARPK pathway inhibitor and methods of use of such signatures.

  本发明提供了确定癌症中可预测对 MARPK 通路抑制剂反应的分子特征的方法和装置，以及使用这些特征的方法。
• Methods of diagnosing and treating cancer in patients having or developing resistance to a first cancer therapy
  申请人：Garraway Levi A.

  公开号：US11078540B2

  公开（公告）日：2021-08-03

  A method of identifying a subject having cancer who is likely to benefit from treatment with a combination therapy with a RAF inhibitor and a second inhibitor is provided. A method of treating cancer in a subject in need thereof is also provided and includes administering to the subject an effective amount of a RAF inhibitor and an effective amount of a second inhibitor, wherein the second inhibitor is a MEK inhibitor, a CRAF inhibitor, a CrkL inhibitor or a TPL2/COT inhibitor. A method of identifying a kinase target that confers resistance to a first inhibitor is also provided.

  本发明提供了一种方法，用于鉴定可能受益于RAF抑制剂和第二抑制剂联合疗法的癌症受试者。还提供了一种治疗有需要的受试者癌症的方法，包括向受试者施用有效量的RAF抑制剂和有效量的第二抑制剂，其中第二抑制剂是MEK抑制剂、CRAF抑制剂、CrkL抑制剂或TPL2/COT抑制剂。还提供了一种鉴定对第一种抑制剂产生抗性的激酶靶点的方法。