N-tert-butyl-6-hydroxy-1-naphthamide | 1019203-23-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: N-tert-butyl-6-hydroxy-1-naphthamide
• 英文别名: N-tert-butyl-6-hydroxynaphthalene-1-carboxamide
• CAS: 1019203-23-6
• 化学式: C₁₅H₁₇NO₂
• 分子量: 243.305
• InChiKey: VPUWVJVXSBPDCR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  49.3
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-氯 -6,7-二甲氧基喹啉 、 N-tert-butyl-6-hydroxy-1-naphthamide 在 铜 吡啶 、 氢氧化钾 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.33h， 生成 N-tert-butyl-6-(6,7-dimethoxyquinolin-4-yl)oxynaphthalene-1-carboxamide
  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
• 作为产物：
  描述：

  6-羟基-1-萘甲酸 、 叔丁胺 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， 反应 8.0h， 以46%的产率得到N-tert-butyl-6-hydroxy-1-naphthamide
  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

• 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.