7-(6,7-dimethoxyquinolin-4-yloxy)-3,4-dihydro-2H-benzo[b][1,4]oxazine | 861880-99-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 7-(6,7-dimethoxyquinolin-4-yloxy)-3,4-dihydro-2H-benzo[b][1,4]oxazine
• 英文别名: 7-(6,7-dimethoxyquinolin-4-yl)oxy-3,4-dihydro-2H-1,4-benzoxazine
• CAS: 861880-99-1
• 化学式: C₁₉H₁₈N₂O₄
• 分子量: 338.363
• InChiKey: CGYKXPVCKITRLS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  61.8
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  7-(6,7-dimethoxyquinolin-4-yloxy)-3,4-dihydro-2H-benzo[b][1,4]oxazine 、 异氰酸甲酯 以 二氯甲烷 为溶剂， 反应 2.0h， 生成 7-((6,7-bis(methyloxy)-4-quinolinyl)oxy)-N-methyl-2,3-dihydro-4H-1,4-benzoxazine-4-carboxamide
  参考文献：
  名称：

  Novel 2,3-Dihydro-1,4-Benzoxazines as Potent and Orally Bioavailable Inhibitors of Tumor-Driven Angiogenesis

  摘要：

  Angiogenesis is vital for solid tumor growth, and its prevention is a proven strategy for the treatment of disease states such as cancer. The vascular endothelial growth factor (VEGF) pathway provides several opportunities by which small molecules can act as inhibitors of endothelial proliferation and migration. Critical to these processes is signaling through VEGFR-2 or the kinase insert domain receptor (KDR) upon stimulation by its ligand VEGF. Herein, we report the discovery of 2,3-dihydro-1,4-benzoxazines as inhibitors of intrinsic KDR activity (IC 50 < 0.1 microM) and human umbilical vein endothelial cell (HUVEC) proliferation with IC 50 < 0.1 microM. More specifically, compound 16 was identified as a potent (KDR: < 1 nM and HUVEC: 4 nM) and selective inhibitor that exhibited efficacy in angiogenic in vivo models. In addition, this series of molecules is typically well-absorbed orally, further demonstrating the 2,3-dihydro-1,4-benzoxazine moiety as a promising platform for generating kinase-based antiangiogenic therapeutic agents.

  DOI：

  10.1021/jm701129j
• 作为产物：
  描述：

  3,4-dihydro-2H-benzo[b][1,4]oxazin-7-ol hydrochloride 、 4-氯 -6,7-二甲氧基喹啉 在 potassium tert-butylate 作用下， 以 N-甲基吡咯烷酮 为溶剂， 反应 18.0h， 以73%的产率得到7-(6,7-dimethoxyquinolin-4-yloxy)-3,4-dihydro-2H-benzo[b][1,4]oxazine
  参考文献：
  名称：

  [EN] BENZOMORPHOLINE DERIVATIVES AND METHODS OF USE
  [FR] DÉRIVÉS DE BENZOMORPHOLINE ET PROCÉDÉS D'UTILISATION

  摘要：

  公开号：

  WO2009058267A3

文献信息

• Compounds and methods of use
  申请人：Potashman Michele

  公开号：US20060241115A1

  公开（公告）日：2006-10-26

  Selected compounds are effective for prophylaxis and treatment of diseases, such as HGF mediated diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving, cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.

  所选化合物对于预防和治疗HGF介导的疾病等具有有效性。本发明涵盖了新颖的化合物、类似物、前药和其药学上可接受的盐，以及用于预防和治疗涉及癌症等疾病和其他疾病或状况的药物组合物和方法。该发明还涉及制备此类化合物的过程，以及在此类过程中有用的中间体。
• Benzomorpholine derivatives and methods of use
  申请人：Harmange Jean-Christophe

  公开号：US20090149454A1

  公开（公告）日：2009-06-11

  Selected benzomorpholine compounds are effective for prophylaxis and treatment of diseases, such as VEGF mediated diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving, cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.

  所选的苯并吗啡类化合物可用于预防和治疗VEGF介导的疾病等疾病。本发明涵盖了新型化合物、类似物、前药和其药学上可接受的盐、制药组合物以及用于预防和治疗癌症等疾病和其他疾病或病症的方法。本发明还涉及制备这样的化合物的方法以及在这样的过程中有用的中间体。
• [EN] BENZOMORPHOLINE DERIVATIVES AND METHODS OF USE<br/>[FR] DÉRIVÉS DE BENZOMORPHOLINE ET PROCÉDÉS D'UTILISATION
  申请人：AMGEN INC

  公开号：WO2009058267A3

  公开（公告）日：2010-06-10
• COMPOUNDS AND METHODS OF USE
  申请人：AMGEN INC.

  公开号：EP1713484A2

  公开（公告）日：2006-10-25
• BENZOMORPHOLINE DERIVATIVES AND METHODS OF USE
  申请人：Amgen, Inc

  公开号：EP2220078B1

  公开（公告）日：2013-05-22