3,4-dihydro-2H-benzo[b][1,4]oxazin-7-ol hydrochloride | 1149370-96-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶嗪类
• 英文名称: 3,4-dihydro-2H-benzo[b][1,4]oxazin-7-ol hydrochloride
• 英文别名: 3,4-Dihydro-2H-1,4-benzoxazin-7-ol hydrochloride；3,4-dihydro-2H-1,4-benzoxazin-7-ol;hydrochloride
• CAS: 1149370-96-6
• 化学式: C₈H₉NO₂*ClH
• 分子量: 187.626
• InChiKey: FGPVQGATPLORHC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.62
• 重原子数：
  12
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  41.5
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  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
• 作为产物：
  描述：

  7-羟基-2H-苯并[b][1,4]噁嗪-3(4H)-酮 在 硼烷四氢呋喃络合物 、 盐酸 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 为溶剂， 反应 0.17h， 以95%的产率得到3,4-dihydro-2H-benzo[b][1,4]oxazin-7-ol hydrochloride
  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

• Benzomorpholine derivatives and methods of use
  申请人：Amgen Inc.

  公开号：US07795254B2

  公开（公告）日：2010-09-14

  Selected benzomorpholine compounds, including 7-((6,7-bis(methyloxy)-4-quinolinyl)oxy)-N-(5 -methyl-3-isoxazolyl)-2,3-dihydro-4H-1,4-benzoxazine-4-carboxamide, 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.

  选择的苯并吗啡类化合物，包括7-((6,7-双(甲氧基)-4-喹啉基)氧基)-N-(5-甲基-3-异噁唑基)-2,3-二氢-4H-1,4-苯并噁嗪-4-羧酰胺，对预防和治疗VEGF介导的疾病有效。该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、药物组合物以及用于预防和治疗癌症等疾病和其他疾患或病况的方法。该发明还涉及制造这些化合物的方法以及在这些方法中有用的中间体。
• BENZOMORPHOLINE DERIVATIVES AND METHODS OF USE
  申请人：Amgen, Inc

  公开号：EP2220078A2

  公开（公告）日：2010-08-25
• US7795254B2
  申请人：——

  公开号：US7795254B2

  公开（公告）日：2010-09-14
• Novel 2,3-Dihydro-1,4-Benzoxazines as Potent and Orally Bioavailable Inhibitors of Tumor-Driven Angiogenesis
  作者：Daniel S. La、Julie Belzile、James V. Bready、Angela Coxon、Thomas DeMelfi、Nicholas Doerr、Juan Estrada、Julie C. Flynn、Shaun R. Flynn、Russell F. Graceffa、Shawn P. Harriman、Jay F. Larrow、Alexander M. Long、Matthew W. Martin、Michael J. Morrison、Vinod F. Patel、Philip M. Roveto、Ling Wang、Matthew M. Weiss、Douglas A. Whittington、Yohannes Teffera、Zhiyang Zhao、Anthony J. Polverino、Jean-Christophe Harmange

  DOI：10.1021/jm701129j

  日期：2008.3.1

  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.
• [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