7-(7H-pyrrolo[2,3-d]pyrimidin-4-yloxy)-3,4-dihydro-2H-benzo[b][1,4]oxazine | 1016989-24-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 7-(7H-pyrrolo[2,3-d]pyrimidin-4-yloxy)-3,4-dihydro-2H-benzo[b][1,4]oxazine
• 英文别名: 7-(7H-pyrrolo[2,3-d]pyrimidin-4-yloxy)-3,4-dihydro-2H-1,4-benzoxazine
• CAS: 1016989-24-4
• 化学式: C₁₄H₁₂N₄O₂
• 分子量: 268.275
• InChiKey: ZJNDCUFIORNHPD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  72.1
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  7-(7H-pyrrolo[2,3-d]pyrimidin-4-yloxy)-3,4-dihydro-2H-benzo[b][1,4]oxazine 、 对甲苯异氰酸酯 以 二氯甲烷 为溶剂， 反应 2.0h， 生成 N-(4-methylphenyl)-7-(7H-pyrrolo[2,3-d]pyrimidin-4-yloxy)-2,3-dihydro-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-氯吡咯并嘧啶 在 caesium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 37.0h， 以52%的产率得到7-(7H-pyrrolo[2,3-d]pyrimidin-4-yloxy)-3,4-dihydro-2H-benzo[b][1,4]oxazine
  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

文献信息

• 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.