N-[(2R)-7-((2-[(cyclopropylcarbonyl)amino]pyridin-4-yl)oxy)-1,2,3,4-tetrahydronaphthalen-2-yl]-3-[(dimethylamino)methyl]-5-(trifluoromethyl)benzamide | 1274816-90-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: N-[(2R)-7-((2-[(cyclopropylcarbonyl)amino]pyridin-4-yl)oxy)-1,2,3,4-tetrahydronaphthalen-2-yl]-3-[(dimethylamino)methyl]-5-(trifluoromethyl)benzamide
• 英文别名: N-[(2R)-7-({2-[(cyclopropylcarbonyl)amino]pyridin-4-yl}oxy)-1,2,3,4-tetrahydronaphthalen-2-yl]-3-[(dimethylamino)methyl]-5-(trifluoromethyl)benzamide；N-[(2R)-7-[2-(cyclopropanecarbonylamino)pyridin-4-yl]oxy-1,2,3,4-tetrahydronaphthalen-2-yl]-3-[(dimethylamino)methyl]-5-(trifluoromethyl)benzamide
• CAS: 1274816-90-8
• 化学式: C₃₀H₃₁F₃N₄O₃
• 分子量: 552.596
• InChiKey: WYRQQURJJXPEAL-XMMPIXPASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  40
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  83.6
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  N-[(2R)-7-((2-[(cyclopropylcarbonyl)amino]pyridin-4-yl)oxy)-1,2,3,4-tetrahydronaphthalen-2-yl]-3-[(dimethylamino)methyl]-5-(trifluoromethyl)benzamide 在 盐酸 作用下， 以 乙醚 为溶剂， 反应 0.42h， 以88%的产率得到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：

  3-溴-5-(三氟甲基)苯甲醛 在 吡啶 、 盐酸 、 正丁基锂 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 四氢呋喃 、 乙醚 、 正己烷 、 二氯甲烷 为溶剂， 反应 3.83h， 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
  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