3-morpholino-1H-naphth[1,2-e]-1,3-oxazin-1-one | 7690-72-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 3-morpholino-1H-naphth[1,2-e]-1,3-oxazin-1-one
• 英文别名: 3-Morpholin-4-ylbenzo[f][1,3]benzoxazin-1-one
• CAS: 7690-72-4
• 化学式: C₁₆H₁₄N₂O₃
• 分子量: 282.299
• InChiKey: OGOAHUWJEYJQRQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  21
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  51.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  2-羟基-1-萘甲酸 在 二溴三苯基膦 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 生成 3-morpholino-1H-naphth[1,2-e]-1,3-oxazin-1-one
  参考文献：
  名称：

  Synthesis, structural elucidation, DNA-PK inhibition, homology modelling and anti-platelet activity of morpholino-substituted-1,3-naphth-oxazines

  摘要：

  A number of new angular 2-morpholino-(substituted)-naphth-1,3-oxazines (compound 10b), linear 2-morpholino-(substituted)-naphth-1,3-oxazines (compounds 13b-c), linear 6, 7 and 9-0-substituted-2-morpholino-(substituted)-naphth-1,3-oxazines (compounds 17-22, 24, and 25) and angular compounds 14-16 and 23 were synthesised. The O-substituent was pyridin-2yl-methyl (15, 18, and 21) pyridin-3yl-methyl (16, 19, and 22) and 4-methylpipreazin-1-yl-ethoxy (23-25). Twelve compounds were tested for their inhibitory effect on collagen induced platelet aggregation and it was found that the most active compounds were compounds 19 and 22 with IC(50) = 55 +/- 4 and 85 +/- 4 mu M, respectively. Furthermore, the compounds were also assayed for their ability to inhibit DNA-dependent protein kinase (DNA-PK) activity. The most active compounds were 18 IC(50) = 0.091 mu M, 24 IC(50) = 0.191 mu M, and 22 IC(50) = 0.331 mu M.Homology modelling was used to build a 3D model of DNA-PK based on the X-ray structure of phosphatidylinositol 3-kinases (PI3Ks). Docking of synthesised compounds within the binding pocket and structure-activity relationships (SAR) analyses of the poses were performed and results agreed well with observed activity. Crown Copyright (C) 2011 Published by Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.05.032

文献信息

• Synthesis, structural elucidation, DNA-PK inhibition, homology modelling and anti-platelet activity of morpholino-substituted-1,3-naphth-oxazines
  作者：Saleh Ihmaid、Jasim Al-Rawi、Christopher Bradley、Michael J. Angove、Murray N. Robertson、Rachel L. Clark

  DOI：10.1016/j.bmc.2011.05.032

  日期：2011.7

  A number of new angular 2-morpholino-(substituted)-naphth-1,3-oxazines (compound 10b), linear 2-morpholino-(substituted)-naphth-1,3-oxazines (compounds 13b-c), linear 6, 7 and 9-0-substituted-2-morpholino-(substituted)-naphth-1,3-oxazines (compounds 17-22, 24, and 25) and angular compounds 14-16 and 23 were synthesised. The O-substituent was pyridin-2yl-methyl (15, 18, and 21) pyridin-3yl-methyl (16, 19, and 22) and 4-methylpipreazin-1-yl-ethoxy (23-25). Twelve compounds were tested for their inhibitory effect on collagen induced platelet aggregation and it was found that the most active compounds were compounds 19 and 22 with IC(50) = 55 +/- 4 and 85 +/- 4 mu M, respectively. Furthermore, the compounds were also assayed for their ability to inhibit DNA-dependent protein kinase (DNA-PK) activity. The most active compounds were 18 IC(50) = 0.091 mu M, 24 IC(50) = 0.191 mu M, and 22 IC(50) = 0.331 mu M.Homology modelling was used to build a 3D model of DNA-PK based on the X-ray structure of phosphatidylinositol 3-kinases (PI3Ks). Docking of synthesised compounds within the binding pocket and structure-activity relationships (SAR) analyses of the poses were performed and results agreed well with observed activity. Crown Copyright (C) 2011 Published by Elsevier Ltd. All rights reserved.