2-methyl-5-(3-morpholin-4-yl-propoxy)phenylamine | 1420998-54-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 2-methyl-5-(3-morpholin-4-yl-propoxy)phenylamine
• 英文别名: 2-Methyl-5-(3-morpholin-4-yl-propoxy)-phenylamine；2-methyl-5-(3-morpholin-4-ylpropoxy)aniline
• CAS: 1420998-54-4
• 化学式: C₁₄H₂₂N₂O₂
• 分子量: 250.341
• InChiKey: YELLOPUPFKYPAU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  47.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-methyl-5-(3-morpholin-4-yl-propoxy)phenylamine 、 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 N-(4'-acetyl-3',5,6-trimethoxybiphenyl-3-yl)-N'-[2-methyl-5-(3-morpholin-4-ylpropoxy)phenyl]urea
  参考文献：
  名称：

  Design, synthesis and biological evaluation of biphenyl urea derivatives as novel VEGFR-2 inhibitors

  摘要：

  VEGFR-2 在血管生成过程中起着关键作用，VEGFR-2 抑制剂已被广泛用于治疗癌症。我们一直在努力寻找强效的新型 VEGFR-2 抑制剂作为抗肿瘤药物，在此过程中，我们发现了一种具有联苯支架的强效先导化合物（HMQ-16）。将 HMQ-16 中的芳基氨基甲酰基重新排列并替换为脲基，产生了一系列新型 VEGFR-2 抑制剂。为了增强与 VEGFR-2 的亲和力，4′-乙酰基被转化为肟基。研究人员设计并合成了 14 种联苯脲衍生物，作为有效的 VEGFR-2 抑制剂。其中六种（T2、T5、T7、T9、T11、T14）表现出与索拉非尼相当的强效 VEGFR-2 抑制活性。化合物 T7 的 IC50 值为 1.08 nM，效力最强。酶和细胞检测结果表明，T7 有可能成为一种有价值的先导化合物，有待进一步优化。

  DOI：

  10.1039/c3md00192j
• 作为产物：
  描述：

  4-(3-bromo-propoxy)-1-methyl-2-nitro-benzene 在 盐酸 、 tin(II) chloride dihdyrate 、 potassium carbonate 作用下， 以 1,4-二氧六环 、 乙醇 、 水 为溶剂， 反应 7.0h， 生成 2-methyl-5-(3-morpholin-4-yl-propoxy)phenylamine
  参考文献：
  名称：

  [EN] OXAZOLE AND THIAZOLE DERIVATIVES AS SELECTIVE PROTEIN KINASE INHIBITORS (C-KIT)
  [FR] DÉRIVÉS D'OXAZOLE ET DE THIAZOLE COMME INHIBITEURS SÉLECTIFS DE PROTÉINES KINASES (C-KIT)

  摘要：

  本发明涉及公式I的化合物或其药用盐：其中R1、R2、R3、A、Q、W和X如描述中所定义。这些化合物选择性地调节、调控和/或抑制由某些与多种人类和动物疾病有关的天然和/或突变的蛋白激酶介导的信号传导，如细胞增殖、代谢、过敏和退行性疾病。更具体地说，这些化合物是强效且选择性的天然和/或突变的c-kit抑制剂。

  公开号：

  WO2013014170A1

文献信息

• SELECTIVE PROTEIN KINASE INHIBITORS
  申请人：Benjahad Abdellah

  公开号：US20140179698A1

  公开（公告）日：2014-06-26

  The present invention relates to compounds of formula I or pharmaceutically acceptable salts thereof: wherein R 1 , R 2 , R 3 , A, Q, W and X are as defined in the description. These compounds selectively modulate, regulate, and/or inhibit signal transduction mediated by certain native and/or mutant protein kinases implicated in a variety of human and animal diseases such as cell proliferative, metabolic, allergic, and degenerative disorders. More particularly, these compounds are potent and selective native and/or mutant c-kit inhibitors.

  本发明涉及式I的化合物或其药学上可接受的盐：其中R1、R2、R3、A、Q、W和X如描述中所定义。这些化合物选择性地调节、调节和/或抑制由某些天然和/或突变的蛋白激酶介导的信号转导，这些蛋白激酶与人类和动物疾病的各种细胞增殖、代谢、过敏和退行性疾病有关。更具体地说，这些化合物是有效的、选择性的天然和/或突变的c-kit抑制剂。
• Selective protein kinase inhibitors
  申请人：Benjahad Abdellah

  公开号：US09168245B2

  公开（公告）日：2015-10-27

  The present invention relates to compounds of formula I or pharmaceutically acceptable salts thereof: wherein R1, R2, R3, A, Q, W and X are as defined in the description. These compounds selectively modulate, regulate, and/or inhibit signal transduction mediated by certain native and/or mutant protein kinases implicated in a variety of human and animal diseases such as cell proliferative, metabolic, allergic, and degenerative disorders. More particularly, these compounds are potent and selective native and/or mutant c-kit inhibitors.

  本发明涉及公式I的化合物或其药学上可接受的盐：其中，R1、R2、R3、A、Q、W和X如描述中所定义。这些化合物有选择性地调节、调节和/或抑制某些与细胞增殖、代谢、过敏和退化性疾病有关的天然和/或突变蛋白激酶介导的信号转导。更具体地说，这些化合物是有效的选择性天然和/或突变c-kit抑制剂。
• Biphenyl derivatives incorporating urea unit as novel VEGFR-2 inhibitors: Design, synthesis and biological evaluation
  作者：Chen Wang、Hongping Gao、Jinyun Dong、Yanmin Zhang、Ping Su、Yaling Shi、Jie Zhang

  DOI：10.1016/j.bmc.2013.11.027

  日期：2014.1

  A series of novel biphenyl urea derivates were synthesized and investigated for their potential to inhibit vascular endothelial growth factor receptor-2 (VEGFR-2). In particular, A7, B3 and B4 displayed significant enzymatic inhibitory activities, with IC50 values of 4.06, 4.55 and 5.26 nM. Compound A7 exhibited potent antiproliferative activity on several cell lines. SAR study suggested that the introduction of methyl at ortho-position of the biphenyl urea and tertiary amine moiety could improve VEGFR-2 inhibitory activity and antitumor effects. Molecular docking indicated that the urea moiety formed four hydrogen bonds with DFG residue. These biphenyl ureas could serve as promising lead compounds for further optimization. (C) 2013 Elsevier Ltd. All rights reserved.
• Discovery of novel VEGFR-2 inhibitors. Part II: Biphenyl urea incorporated with salicylaldoxime
  作者：Hongping Gao、Ping Su、Yaling Shi、Xiuxiu Shen、Yanmin Zhang、Jinyun Dong、Jie Zhang

  DOI：10.1016/j.ejmech.2014.11.032

  日期：2015.1

  A series of novel VEGFR-2 inhibitors containing oxime as hinge binding fragment were described. A strategy of pseudo six-membered ring formed through intramolecular hydrogen bond was employed to mimic the planar quinazoline. The oxime group was firstly introduced to interact with hinge region of VEGFR-2. Most of compounds tested showed moderate to high VEGFR-2 inhibitory activity. In particular, 121, 12p and 12y exhibited significant enzymatic inhibitory activity as well as potent antiproliferative activity against cancer cells. Molecular docking suggested that the salicylaldoxime formed two hydrogen bonds with hinge region. These biphenylureas could serve as promising lead compounds for developing novel anticancer agents. (C) 2014 Elsevier Masson SAS. All rights reserved.
• OXAZOLE AND THIAZOLE DERIVATIVES AS SELECTIVE PROTEIN KINASE INHIBITORS (C-KIT)
  申请人：AB Science

  公开号：EP2736904A1

  公开（公告）日：2014-06-04