N-Cyclopropyl-6-[(6,7-dimethoxy-4-quinazolinyl)oxy]-1-naphthalenecarboxamide | 861880-16-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: N-Cyclopropyl-6-[(6,7-dimethoxy-4-quinazolinyl)oxy]-1-naphthalenecarboxamide
• 英文别名: N-cyclopropyl-6-(6,7-dimethoxyquinazolin-4-yl)oxynaphthalene-1-carboxamide
• CAS: 861880-16-2
• 化学式: C₂₄H₂₁N₃O₄
• 分子量: 415.448
• InChiKey: JLBAXNKYJZOYGQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  82.6
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  、 环丙胺 在 碳酸氢钠 作用下， 以 二氯甲烷 为溶剂， 以16 mg的产率得到N-Cyclopropyl-6-[(6,7-dimethoxy-4-quinazolinyl)oxy]-1-naphthalenecarboxamide
  参考文献：
  名称：

  Evaluation of a Series of Naphthamides as Potent, Orally Active Vascular Endothelial Growth Factor Receptor-2 Tyrosine Kinase Inhibitors

  摘要：

  We have previously shown N-arylnaphthamides can be potent inhibitors of vascular endothelial growth factor receptors (VEGFRs). N-Alkyl and N-unsubstituted naphthamides were prepared and found to yield nanomolar inhibitors of VEGFR-2 (KDR) with an improved selectivity profile against a panel of tyrosine and serine/threonine kinases. The inhibitory activity of this series was retained at the cellular level. Naphthamides 3, 20, and 22 exhibited good pharmacokinetics following oral dosing and showed potent inhibition of VEGF-induced angiogenesis in the rat corneal model. Once-daily oral administration of 22 for 14 days led to 85% inhibition of established HT29 colon cancer and Calu-6 lung cancer xenografts at doses of 10 and 20 mg/kg, respectively.

  DOI：

  10.1021/jm701098w

文献信息

• Compounds and methods of use
  申请人：Potashman Michele

  公开号：US20090176774A1

  公开（公告）日：2009-07-09

  Selected compounds are effective for prophylaxis and treatment of diseases, such as HGF mediated diseases. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving, cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.

  所选化合物对于预防和治疗HGF介导的疾病等疾病有效。该发明涵盖了新的化合物、类似物、前药和其药学上可接受的盐、制药组合物以及预防和治疗癌症等疾病和其他疾病或情况的方法。该发明还涉及制造这些化合物的过程以及在这些过程中有用的中间体。
• US7435823B2
  申请人：——

  公开号：US7435823B2

  公开（公告）日：2008-10-14
• US8178557B2
  申请人：——

  公开号：US8178557B2

  公开（公告）日：2012-05-15
• Evaluation of a Series of Naphthamides as Potent, Orally Active Vascular Endothelial Growth Factor Receptor-2 Tyrosine Kinase Inhibitors
  作者：Matthew M. Weiss、Jean-Christophe Harmange、Anthony J. Polverino、David Bauer、Loren Berry、Virginia Berry、George Borg、James Bready、Danlin Chen、Deborah Choquette、Angela Coxon、Tom DeMelfi、Nicholas Doerr、Juan Estrada、Julie Flynn、Russell F. Graceffa、Shawn P. Harriman、Stephen Kaufman、Daniel S. La、Alexander Long、Sesha Neervannan、Vinod F. Patel、Michele Potashman、Kelly Regal、Phillip M. Roveto、Michael L. Schrag、Charlie Starnes、Andrew Tasker、Yohannes Teffera、Douglas A. Whittington、Roger Zanon

  DOI：10.1021/jm701098w

  日期：2008.3.1

  We have previously shown N-arylnaphthamides can be potent inhibitors of vascular endothelial growth factor receptors (VEGFRs). N-Alkyl and N-unsubstituted naphthamides were prepared and found to yield nanomolar inhibitors of VEGFR-2 (KDR) with an improved selectivity profile against a panel of tyrosine and serine/threonine kinases. The inhibitory activity of this series was retained at the cellular level. Naphthamides 3, 20, and 22 exhibited good pharmacokinetics following oral dosing and showed potent inhibition of VEGF-induced angiogenesis in the rat corneal model. Once-daily oral administration of 22 for 14 days led to 85% inhibition of established HT29 colon cancer and Calu-6 lung cancer xenografts at doses of 10 and 20 mg/kg, respectively.