7-((2-[(methylamino)carbonyl]pyridin-4-yl)oxy)-1,2,3,4-tetrahydronaphthalene-2-carboxylic acid | 1274816-79-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 7-((2-[(methylamino)carbonyl]pyridin-4-yl)oxy)-1,2,3,4-tetrahydronaphthalene-2-carboxylic acid
• 英文别名: 7-[2-(Methylcarbamoyl)pyridin-4-yl]oxy-1,2,3,4-tetrahydronaphthalene-2-carboxylic acid
• CAS: 1274816-79-3
• 化学式: C₁₈H₁₈N₂O₄
• 分子量: 326.352
• InChiKey: QPGHBKUZYYEMBH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  88.5
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  7-((2-[(methylamino)carbonyl]pyridin-4-yl)oxy)-1,2,3,4-tetrahydronaphthalene-2-carboxylic acid 在 4-二甲氨基吡啶 、 氨 、 氢气 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 5.0h， 生成 4-([7-(([3-(aminomethyl)-5-(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
• 作为产物：
  描述：

  7-甲氧基-1-萘满酮 在 硫酸 、 palladium 10% on activated carbon 、 氢溴酸 、 氢气 、 sodium hydride 、 caesium carbonate 、 溶剂黄146 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 65.0~100.0 ℃ 、206.85 kPa 条件下， 反应 5.67h， 生成 7-((2-[(methylamino)carbonyl]pyridin-4-yl)oxy)-1,2,3,4-tetrahydronaphthalene-2-carboxylic acid
  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