6-[(6,7-Dimethoxy-4-quinolinyl)oxy]-N-(1-methylethyl)-1-naphthalenecarboxamide | 1016989-33-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 6-[(6,7-Dimethoxy-4-quinolinyl)oxy]-N-(1-methylethyl)-1-naphthalenecarboxamide
• 英文别名: 6-(6,7-dimethoxyquinolin-4-yl)oxy-N-propan-2-ylnaphthalene-1-carboxamide
• CAS: 1016989-33-5
• 化学式: C₂₅H₂₄N₂O₄
• 分子量: 416.477
• InChiKey: REKQXOMQYIHNKM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  69.7
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  6-(6,7-Dimethoxyquinolin-4-yloxy)-1-naphthoyl chloride 、 异丙胺 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以287 mg的产率得到6-[(6,7-Dimethoxy-4-quinolinyl)oxy]-N-(1-methylethyl)-1-naphthalenecarboxamide
  参考文献：
  名称：

  Naphthamides as Novel and Potent Vascular Endothelial Growth Factor Receptor Tyrosine Kinase Inhibitors: Design, Synthesis, and Evaluation

  摘要：

  A series of naphthyl-based compounds were synthesized as potential inhibitors of vascular endothelial growth factor (VEGF) receptors. Investigations of structure-activity relationships led to the identification of a series of naphthamides that are potent inhibitors of the VEGF receptor tyrosine kinase family. Numerous analogues demonstrated low nanomolar inhibition of VEGF-dependent human umbilical vein endothelial cell (HUVEC) proliferation, and of these several compounds possessed favorable pharmacokinetic (PK) profiles. In particular, compound 48 demonstrated significant antitumor efficacy against established HT29 human colon adenocarcinoma xenografts implanted in athymic mice. A full account of the preparation, structure-activity relationships, pharmacokinetic properties, and pharmacology of analogues within this series is presented.

  DOI：

  10.1021/jm701097z

文献信息

• 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.
• Naphthamides as Novel and Potent Vascular Endothelial Growth Factor Receptor Tyrosine Kinase Inhibitors: Design, Synthesis, and Evaluation
  作者：Jean-Christophe Harmange、Matthew M. Weiss、Julie Germain、Anthony J. Polverino、George Borg、James Bready、Danlin Chen、Deborah Choquette、Angela Coxon、Tom DeMelfi、Lucian DiPietro、Nicholas Doerr、Juan Estrada、Julie Flynn、Russell F. Graceffa、Shawn P. Harriman、Stephen Kaufman、Daniel S. La、Alexander Long、Matthew W. Martin、Sesha Neervannan、Vinod F. Patel、Michele Potashman、Kelly Regal、Phillip M. Roveto、Michael L. Schrag、Charlie Starnes、Andrew Tasker、Yohannes Teffera、Ling Wang、Ryan D. White、Douglas A. Whittington、Roger Zanon

  DOI：10.1021/jm701097z

  日期：2008.3.1

  A series of naphthyl-based compounds were synthesized as potential inhibitors of vascular endothelial growth factor (VEGF) receptors. Investigations of structure-activity relationships led to the identification of a series of naphthamides that are potent inhibitors of the VEGF receptor tyrosine kinase family. Numerous analogues demonstrated low nanomolar inhibition of VEGF-dependent human umbilical vein endothelial cell (HUVEC) proliferation, and of these several compounds possessed favorable pharmacokinetic (PK) profiles. In particular, compound 48 demonstrated significant antitumor efficacy against established HT29 human colon adenocarcinoma xenografts implanted in athymic mice. A full account of the preparation, structure-activity relationships, pharmacokinetic properties, and pharmacology of analogues within this series is presented.