N-[5-[(6-oxo-5H-benzo[c][1,8]naphthyridin-1-yl)amino]pyrimidin-2-yl]benzamide | 1432308-22-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: N-[5-[(6-oxo-5H-benzo[c][1,8]naphthyridin-1-yl)amino]pyrimidin-2-yl]benzamide
• CAS: 1432308-22-9
• 化学式: C₂₃H₁₆N₆O₂
• 分子量: 408.419
• InChiKey: YQONVVWDOUUEGH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  31
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  109
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  2-乙氧羰基苯硼酸 在 2-双环己基膦-2',6'-二甲氧基联苯 、 palladium diacetate 、 potassium carbonate 、 sodium t-butanolate 、 2-二环己基磷-2,4,6-三异丙基联苯 作用下， 以 1,4-二氧六环 、 水 为溶剂， 生成 N-[5-[(6-oxo-5H-benzo[c][1,8]naphthyridin-1-yl)amino]pyrimidin-2-yl]benzamide
  参考文献：
  名称：

  SAR and evaluation of novel 5H-benzo[c][1,8]naphthyridin-6-one analogs as Aurora kinase inhibitors

  摘要：

  Several potent Aurora kinase inhibitors derived from 5H-benzo[c][1,8]naphthyridin-6-one scaffold were identified. A crystal structure of Aurora kinase A in complex with an initial hit revealed a binding mode of the inhibitor within the ATP binding site and provided insight for structure-guided compound optimization. Subsequent SAR campaign provided a potent and selective pan Aurora inhibitor, which demonstrated potent target modulation and antiproliferative effects in the pancreatic cell line, MIAPaCa-2. Furthermore, this compound inhibited phosphorylation of histone H3 (pHH3) in mouse bone morrow upon oral administration, which is consistent with inhibition of Aurora kinase B activity. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.03.008

文献信息

• SAR and evaluation of novel 5H-benzo[c][1,8]naphthyridin-6-one analogs as Aurora kinase inhibitors
  作者：Srinivasa Karra、Yufang Xiao、Xiaoling Chen、Lesley Liu-Bujalski、Bayard Huck、Amanda Sutton、Andreas Goutopoulos、Ben Askew、Kristopher Josephson、Xuliang Jiang、Adam Shutes、Vikram Shankar、Tom Noonan、Gaianne Garcia-Berrios、Rong Dong、Mohanraj Dhanabal、Hui Tian、Zhenxiong Wang、A. Clark、Samantha Goodstal

  DOI：10.1016/j.bmcl.2013.03.008

  日期：2013.5

  Several potent Aurora kinase inhibitors derived from 5H-benzo[c][1,8]naphthyridin-6-one scaffold were identified. A crystal structure of Aurora kinase A in complex with an initial hit revealed a binding mode of the inhibitor within the ATP binding site and provided insight for structure-guided compound optimization. Subsequent SAR campaign provided a potent and selective pan Aurora inhibitor, which demonstrated potent target modulation and antiproliferative effects in the pancreatic cell line, MIAPaCa-2. Furthermore, this compound inhibited phosphorylation of histone H3 (pHH3) in mouse bone morrow upon oral administration, which is consistent with inhibition of Aurora kinase B activity. (C) 2013 Elsevier Ltd. All rights reserved.