6-(6,7-dimethoxyquinolin-4-ylamino)-1-naphthoic acid | 861880-98-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 6-(6,7-dimethoxyquinolin-4-ylamino)-1-naphthoic acid
• 英文别名: 6-[(6,7-Dimethoxy-4-quinolinyl)amino]-1-naphthalenecarboxylic acid；6-[(6,7-dimethoxyquinolin-4-yl)amino]naphthalene-1-carboxylic acid
• CAS: 861880-98-0
• 化学式: C₂₂H₁₈N₂O₄
• 分子量: 374.396
• InChiKey: FNLCMXSZQANUSY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  80.7
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  6-(6,7-dimethoxyquinolin-4-ylamino)-1-naphthoic acid 、 对氯苯胺 在 N-羟基-7-氮杂苯并三氮唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 以49%的产率得到N-(4-chlorophenyl)-6-[(6,7-dimethoxyquinolin-4-yl)amino]naphthalene-1-carboxamide
  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
• 作为产物：
  描述：

  methyl 6-(6,7-dimethoxyquinolin-4-ylamino)-1-naphthoate 在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 反应 8.0h， 以94%的产率得到6-(6,7-dimethoxyquinolin-4-ylamino)-1-naphthoic acid
  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

• 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.