4-([7-(([4-cyano-3-(trifluoromethyl)phenyl]amino)carbonyl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy)-N-methylpyridine-2-carboxamide | 1274816-84-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 4-([7-(([4-cyano-3-(trifluoromethyl)phenyl]amino)carbonyl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy)-N-methylpyridine-2-carboxamide
• 英文别名: 4-[[7-[[4-cyano-3-(trifluoromethyl)phenyl]carbamoyl]-5,6,7,8-tetrahydronaphthalen-2-yl]oxy]-N-methylpyridine-2-carboxamide
• CAS: 1274816-84-0
• 化学式: C₂₆H₂₁F₃N₄O₃
• 分子量: 494.473
• InChiKey: BBWCBHZHXCUGQG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  36
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  104
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  4-([7-(([4-cyano-3-(trifluoromethyl)phenyl]amino)carbonyl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy)-N-methylpyridine-2-carboxamide 在 氨 、 氢气 、 盐酸 作用下， 以 甲醇 、 水 、 乙醚 、 二氯甲烷 为溶剂， 反应 5.0h， 以52%的产率得到4-([7-(([4-(aminomethyl)-3-(trifluoromethyl)phenyl]amino)carbonyl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy)-N-methylpyridine-2-carboxamide hydrochloride
  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：

  7-羟基-1,2,3,4-四氢-萘-2-羧酸 在 4-二甲氨基吡啶 、 caesium carbonate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 4-([7-(([4-cyano-3-(trifluoromethyl)phenyl]amino)carbonyl)-5,6,7,8-tetrahydronaphthalen-2-yl]oxy)-N-methylpyridine-2-carboxamide
  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