[4,7']bis-isoquinolinyl-1-yl-(4-tert-butylphenyl)amine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: [4,7']bis-isoquinolinyl-1-yl-(4-tert-butylphenyl)amine
• 英文别名: [4,7']biisoquinolinyl-1-yl-(4-tert-butyl-phenyl)-amine；[4,7']biisoquinolinyl-1-yl-4-(tert-butyl-phenyl)-amine；N-(4-tert-butylphenyl)-4-(isoquinolin-7-yl)isoquinolin-1-amine；N-(4-tert-butylphenyl)-4-isoquinolin-7-ylisoquinolin-1-amine
• 化学式: C₂₈H₂₅N₃
• 分子量: 403.527
• InChiKey: IXXYIIXBZSGESQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.5
• 重原子数：
  31
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  37.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  4-溴异喹啉 在 盐酸 、 正丁基锂 、 sodium tungstate (VI) dihydrate 、 双氧水 、 三氯氧磷 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醇 、 正己烷 、 溶剂黄146 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 51.09h， 生成 [4,7']bis-isoquinolinyl-1-yl-(4-tert-butylphenyl)amine
  参考文献：
  名称：

  The Synthesis of a Novel Inhibitor of B-Raf Kinase

  摘要：

  A scaleable synthetic route to [4,7']bis-isoquinolinyl-1-yl-(2-tert-butyl-pyrimidine-5-yl)amine (1), an inhibitor of B-Raf kinase is described. The key step in the synthesis is the Pd-catalyzed Negishi coupling of 4-bromo-1-chloroisoquinoline with trifluoromethanesulfonic acid isoquinoline-7-yl ester to yield 1-chloro-[4,7']bis-isoquinolinyl. This intermediate is transformed to the desired drug substance in one additional step, by reaction with 2-tert-butyl-5-aminopyrimidine in the presence of NaH. A special focus was put on the finally successful removal of traces of Zn and Pd in the drug substance, which came from the Negishi coupling.

  DOI：

  10.1021/op0501601

文献信息

• [EN] 1,4-DISUBSTITUTED ISOQUINILONE DERIVATIVES AS RAF-KINASE INHIBITORS USEFUL FOR THE TREATMENT OF PROLIFERATIVE DISEASES<br/>[FR] DERIVES D'ISOQUINILONE 1,4-DISUBSTITUES EN TANT QU'INHIBITEURS DE RAF-KINASE UTILES POUR LE TRAITEMENT DE MALADIES PROLIFERANTES
  申请人：NOVARTIS AG

  公开号：WO2005028444A1

  公开（公告）日：2005-03-31

  This invention relates to compounds of formula (I) wherein the variable substituents are described herein. The compounds are useful for the treatment of conditions and diseases characterized by an aberrant MAP kinase signaling pathway, such as cancer.

  本发明涉及式（I）化合物，其中变量取代基在本文中描述。这些化合物可用于治疗由异常的MAP激酶信号通路引起的疾病和症状，如癌症。
• 1,4-Disubstituted isoquinilone derivatives as raf-kinase inhibitors useful for the treatment of proliferative diseases
  申请人：Fink Anne Cynthia

  公开号：US20070060582A1

  公开（公告）日：2007-03-15

  This invention relates to compounds of the formula (I) wherein the variable substituents are described herein. The compounds are useful for the treatment of conditions and diseases characterized by an aberrant MAP kinase signaling pathway, such as cancer.

  本发明涉及公式（I）中变量取代基的化合物，所述的化合物可用于治疗由异常MAP激酶信号通路引起的疾病和症状，例如癌症。
• Methods for treating proliferative diseases and for monitoring the effectiveness of treatment of proliferative diseases
  申请人：Hu Ping

  公开号：US20070099250A1

  公开（公告）日：2007-05-03

  The present invention relates to phosphoproteins useful as biomarkers for identifying and treating patients suffering from diseases characterized by an aberrant MAP kinase signaling pathway, for example proliferative diseases like certain cancers, monitoring the efficacy of treatment of patients having the disease by administering Raf kinase inhibitors and diagnosing the disease in patients.
• PHARMACEUTICAL COMBINATIONS COMPRISING A MTOR INHIBITOR AND A RAF KINASE INHIBITOR
  申请人：Lane Heidi

  公开号：US20090105285A1

  公开（公告）日：2009-04-23

  A pharmaceutical combination comprising an mTOR inhibitor and a Raf kinase inhibitor and its use.
• The Synthesis of a Novel Inhibitor of B-Raf Kinase
  作者：Donatienne Denni-Dischert、Wolfgang Marterer、Markus Bänziger、Naeem Yusuff、David Batt、Tim Ramsey、Peng Geng、Walter Michael、Run-Ming B. Wang、Francis Taplin,、Richard Versace、David Cesarz、Lawrence B. Perez

  DOI：10.1021/op0501601

  日期：2006.1.1

  A scaleable synthetic route to [4,7']bis-isoquinolinyl-1-yl-(2-tert-butyl-pyrimidine-5-yl)amine (1), an inhibitor of B-Raf kinase is described. The key step in the synthesis is the Pd-catalyzed Negishi coupling of 4-bromo-1-chloroisoquinoline with trifluoromethanesulfonic acid isoquinoline-7-yl ester to yield 1-chloro-[4,7']bis-isoquinolinyl. This intermediate is transformed to the desired drug substance in one additional step, by reaction with 2-tert-butyl-5-aminopyrimidine in the presence of NaH. A special focus was put on the finally successful removal of traces of Zn and Pd in the drug substance, which came from the Negishi coupling.