N-(4-([(7R)-7-amino-5,6,7,8-tetrahydronaphthalen-2-yl]oxy)pyridin-2-yl)cyclopropanecarboxamide | 1274817-09-2

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: N-(4-([(7R)-7-amino-5,6,7,8-tetrahydronaphthalen-2-yl]oxy)pyridin-2-yl)cyclopropanecarboxamide
• CAS: 1274817-09-2
• 化学式: C₁₉H₂₁N₃O₂
• 分子量: 323.395
• InChiKey: BLXRXMIPVUJHLR-OAHLLOKOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.04
• 重原子数：
  24.0
• 可旋转键数：
  4.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  77.24
• 氢给体数：
  2.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  3-[(dimethylamino)methyl]-5-(trifluoromethyl)benzoic acid lithium salt 、 N-(4-([(7R)-7-amino-5,6,7,8-tetrahydronaphthalen-2-yl]oxy)pyridin-2-yl)cyclopropanecarboxamide 在 吡啶 、 盐酸 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 乙醚 为溶剂， 反应 0.42h， 生成 N-[(2R)-7-((2-[(cyclopropylcarbonyl)amino]pyridin-4-yl)oxy)-1,2,3,4-tetrahydronaphthalen-2-yl]-3-[(dimethylamino)methyl]-5-(trifluoromethyl)benzamide dihydrochloride
  参考文献：
  名称：

  Design and Optimization of Potent and Orally Bioavailable Tetrahydronaphthalene Raf Inhibitors

  摘要：

  Inhibition of mutant B-Raf signaling, through either direct inhibition of the enzyme or inhibition of MEK, the direct substrate of Raf, has been demonstrated preclinically to inhibit tumor growth. Very recently, treatment of B-Raf mutant melanoma patients with a selective B-Raf inhibitor has resulted in promising preliminary evidence of antitumor activity. This article describes the design and optimization of tetrahydronaphthalene-derived compounds as potent inhibitors of the Raf pathway in vitro and in vivo. These compounds possess good pharmacokinetic properties in rodents and inhibit B-Raf mutant tumor growth in mouse xenograft models.

  DOI：

  10.1021/jm101479y
• 作为产物：
  描述：

  N-(4-methoxybenzyl)-4-nitropyridin-2-amine 1-oxide 在 吡啶 、 caesium carbonate 、 苯甲醚 、 三氟乙酸 、 三氯氧磷 作用下， 以 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 反应 32.0h， 生成 N-(4-([(7R)-7-amino-5,6,7,8-tetrahydronaphthalen-2-yl]oxy)pyridin-2-yl)cyclopropanecarboxamide
  参考文献：
  名称：

  Design and Optimization of Potent and Orally Bioavailable Tetrahydronaphthalene Raf Inhibitors

  摘要：

  Inhibition of mutant B-Raf signaling, through either direct inhibition of the enzyme or inhibition of MEK, the direct substrate of Raf, has been demonstrated preclinically to inhibit tumor growth. Very recently, treatment of B-Raf mutant melanoma patients with a selective B-Raf inhibitor has resulted in promising preliminary evidence of antitumor activity. This article describes the design and optimization of tetrahydronaphthalene-derived compounds as potent inhibitors of the Raf pathway in vitro and in vivo. These compounds possess good pharmacokinetic properties in rodents and inhibit B-Raf mutant tumor growth in mouse xenograft models.

  DOI：

  10.1021/jm101479y