1-phenylamino-5H-benzo[c][1,8]naphthyridin-6-one | 1186375-27-8

• 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: 1-phenylamino-5H-benzo[c][1,8]naphthyridin-6-one
• 英文别名: 1-anilino-5H-benzo[c][1,8]naphthyridin-6-one
• CAS: 1186375-27-8
• 化学式: C₁₈H₁₃N₃O
• 分子量: 287.321
• InChiKey: ONKLLWFAONHNLU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  54
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-phenylamino-5H-benzo[c][1,8]naphthyridin-6-one 在 三氯氧磷 作用下， 以 异丙醇 为溶剂， 生成 N1-benzyl-N6-(2-dimethylamino-ethyl)-benzo[c][1,8]naphthyridine-1,6-diamine trifluoroacetate
  参考文献：
  名称：

  [EN] PROTEIN KINASE INHIBITORS AND USE THEREOF
  [FR] INHIBITEURS DE PROTÉINE KINASE ET LEUR UTILISATION

  摘要：

  揭示了苯并萘啶衍生物化合物及其类似物，包括含有这些化合物的药物组合物以及制备这些化合物的方法。这些化合物在治疗对激酶信号传导抑制、调节或调控敏感的疾病中很有用。

  公开号：

  WO2009108670A1
• 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 、 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 1-phenylamino-5H-benzo[c][1,8]naphthyridin-6-one
  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

• PROTEIN KINASE INHIBITORS AND USE THEREOF
  申请人：Huck Bayard R.

  公开号：US20110053906A1

  公开（公告）日：2011-03-03

  Disclosed are benzonaphthyridinyl derivative compounds and analogs thereof, pharmaceutical compositions comprising such compounds and processes for preparing the same. The compounds are useful in the treatment of diseases amenable to kinase signal transduction inhibition, regulation or modulation.

  本发明揭示了苯并萘啉衍生物化合物及其类似物，包括含有这些化合物的制药组合物和制备这些化合物的过程。这些化合物可用于治疗易于激酶信号传导抑制、调节或调控的疾病。
• Protein kinase inhibitors and use thereof
  申请人：Huck Bayard R.

  公开号：US08735584B2

  公开（公告）日：2014-05-27

  Disclosed are benzonaphthyridinyl derivative compounds and analogs thereof, pharmaceutical compositions comprising such compounds and processes for preparing the same. The compounds are useful in the treatment of diseases amenable to kinase signal transduction inhibition, regulation or modulation.

  本发明涉及苯并萘啶衍生物化合物及其类似物，包括含有这些化合物的药物组合物以及制备这些化合物的方法。这些化合物在治疗易受激酶信号转导抑制、调节或调制的疾病中很有用。
• US8735584B2
  申请人：——

  公开号：US8735584B2

  公开（公告）日：2014-05-27
• [EN] PROTEIN KINASE INHIBITORS AND USE THEREOF<br/>[FR] INHIBITEURS DE PROTÉINE KINASE ET LEUR UTILISATION
  申请人：MERCK SERONO SA

  公开号：WO2009108670A1

  公开（公告）日：2009-09-03

  Disclosed are benzonaphthyridinyl derivative compounds and analogs thereof, pharmaceutical compositions comprising such compounds and processes for preparing the same. The compounds are useful in the treatment of diseases amenable to kinase signal transduction inhibition, regulation or modulation.

  揭示了苯并萘啶衍生物化合物及其类似物，包括含有这些化合物的药物组合物以及制备这些化合物的方法。这些化合物在治疗对激酶信号传导抑制、调节或调控敏感的疾病中很有用。
• 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.